ruleID organism gene nodeID refseq accession GenBank accession HMM accession ARO accession mutation variation type context drug drug class phenotype clinical category breakpoint breakpoint standard PMID evidence code evidence grade evidence limitations rule curation note NGO0001 s__Neisseria gonorrhoeae 16S - NZ_AP019853.2:1155759-1157299 - - ARO:3003495 c.1191C>T Nucleotide variant detected acquired spectinomycin - nonwildtype R MIC >64 mg/L EUCAST v14.0 (2024) "2138078, 10770780" "ECO:0001103 natural variation mutant evidence, ECO:0001113 point mutation phenotypic evidence" moderate statistical geno/pheno evidence but no experimental evidence "Core ribosomal RNA gene, mutation confers spectinomycin resistance. Is C1191T in NCBI ReferenceGeneCatalog, C1189T in CARD. Not enough data to evaluate phenotype codification from geno-pheno data. NWT R assigned according to experimental evidence." NGO0002 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2059A>G][4] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 20585125 ECO:0001103 natural variation mutant evidence strong "Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2045A>G substitution (2059A>G in E. coli; 2062 in AMRfinderplus). Experimental evidence from growth under antibiotic pressure, but not from transformation experiments (PMID 20585125)." NGO0003 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2059A>G][3] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 20585125 ECO:0001103 natural variation mutant evidence strong "Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2045A>G substitution (2059A>G in E. coli; 2062 in AMRfinderplus). Experimental evidence from growth under antibiotic pressure, but not from transformation experiments (PMID 20585125)." NGO0004 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2059A>G][2] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 20585125 ECO:0001103 natural variation mutant evidence moderate statistical geno/pheno evidence but no experimental evidence Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2045A>G substitution (2059A>G in E. coli; 2062 in AMRfinderplus). NGO0005 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2059A>G][1] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 20585125 ECO:0001103 natural variation mutant evidence moderate statistical geno/pheno evidence but no experimental evidence Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2045A>G substitution (2059A>G in E. coli; 2062 in AMRfinderplus). No clear evidence on whether 1 mutated copy exceeds the ECOFF. NGO0006 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2058A>G][4] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 33139288 ECO:0001103 natural variation mutant evidence strong "Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2044A>G substitution (2058A>G in E. coli). Found in 3 and 4 mutated copies in PMID 33139288. Loss-of function of mtrC increases susceptibility to azithromycin, beta-lactams, tetracyclines and ciprofloxacin. PMID 32807804 reports particularly strong effects for azithromycin. Mutation not in the AMRfinderplus database." NGO0007 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2058A>G][3] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 33139288 ECO:0001103 natural variation mutant evidence strong "Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2044A>G substitution (2058A>G in E. coli). Found in 3 and 4 mutated copies in PMID 33139288. Loss-of function of mtrC increases susceptibility to azithromycin, beta-lactams, tetracyclines and ciprofloxacin. PMID 32807804 reports particularly strong effects for azithromycin. Mutation not in the AMRfinderplus database." NGO0008 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2611C>T][4] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 12183262 ECO:0001103 natural variation mutant evidence strong Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2597C>T substitution (2611C>T in E. coli; 2617 in AMRfinderplus). Found in different copy numbers in clinical and spontaneous mutants in PMID 12183262. NGO0009 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2611C>T][3] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 12183262 ECO:0001103 natural variation mutant evidence strong Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2597C>T substitution (2611C>T in E. coli; 2617 in AMRfinderplus). Found in different copy numbers in clinical and spontaneous mutants in PMID 12183262. NGO0010 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2611C>T][2] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 12183262 ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2597C>T substitution (2611C>T in E. coli; 2617 in AMRfinderplus). Found in different copy numbers in clinical and spontaneous mutants in PMID 12183262 (1 strain with 2 mutated copies with MIC = 1 mg/L, just on the ECOFF)." NGO0011 s__Neisseria gonorrhoeae 23S - NC_002946.2:1119158-1116249 - - ARO:3004836 c.[2611C>T][1] Nucleotide variant detected in multi-copy gene acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 12183262 ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "Wildtype core gene in four copies. Not expected to confer drug resistance unless some of the copies are mutated. 23S rDNA 2597C>T substitution (2611C>T in E. coli; 2617 in AMRfinderplus). Found in different copy numbers in clinical and spontaneous mutants in PMID 12183262 (1 strain with 1 mutated copy with MIC = 0.5 mg/L, below the ECOFF). No clear evidence on whether 1 mutated copy exceeds the ECOFF." NGO0012 s__Neisseria gonorrhoeae blaTEM-1 blaTEM-1 WP_000027057.1 - - ARO:3000873 - Gene presence detected acquired benzylpenicillin - nonwildtype R MIC >1 mg/L EUCAST v14.0 (2024) "11585791, 25149062" ECO:0000005 enzymatic activity assay evidence strong The presence of a TEM beta-lactamase in a plasmid in N. gonorrhoeae causes high-level resistance to benzylpenicillin NGO0013 s__Neisseria gonorrhoeae blaTEM-135 blaTEM-135 WP_015058868.1 - - ARO:3000999 - Gene presence detected acquired benzylpenicillin - nonwildtype R MIC >1 mg/L EUCAST v14.0 (2024) "11585791, 25149062" ECO:0000005 enzymatic activity assay evidence strong The presence of a TEM beta-lactamase in a plasmid in N. gonorrhoeae causes high-level resistance to benzylpenicillin NGO0014 s__Neisseria gonorrhoeae folP - WP_003702942.1 - - ARO:3004873 p.Arg228Ser Protein variant detected acquired - sulfonamide antibiotic nonwildtype R not applicable EUCAST v14.0 (2024) "27432602, 15673729" "ECO:0001113 point mutation phenotypic evidence, ECO:0001103 natural variation mutant evidence" moderate "statistical geno/pheno evidence but no experimental evidence, low clinical relevance" "Wild type gene encoding dihydropteroate synthase, mutation confers resistance to sulfonamides. Originally described in N. meningitidis and can be tracked in N. gonorrhoeae for surveillance purposes. No MIC data available for geno-pheno comparisons, NWT R assigned as phenotype according to experimental evidence. " NGO0015 s__Neisseria gonorrhoeae folP - WP_003702942.1 - - ARO:3004873 p.Phe31Leu Protein variant detected acquired - sulfonamide antibiotic nonwildtype R not applicable EUCAST v14.0 (2024) 7642493 "ECO:0001113 point mutation phenotypic evidence, ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence" weak "lacks evidence for this species, low clinical relevance" "Wild type gene encoding dihydropteroate synthase, mutation confers resistance to sulfonamides. Originally described in N. meningitidis and can be tracked in N. gonorrhoeae for surveillance purposes. No MIC data available for geno-pheno comparisons, NWT R assigned as phenotype according to experimental evidence." NGO0016 s__Neisseria gonorrhoeae folP - WP_003702942.1 - - ARO:3004873 p.Gly194Cys Protein variant detected acquired - sulfonamide antibiotic nonwildtype R not applicable EUCAST v14.0 (2024) 7642493 "ECO:0001113 point mutation phenotypic evidence, ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence" weak "lacks evidence for this species, low clinical relevance" "Wild type gene encoding dihydropteroate synthase, mutation confers resistance to sulfonamides. Originally described in N. meningitidis and can be tracked in N. gonorrhoeae for surveillance purposes. No MIC data available for geno-pheno comparisons, NWT R assigned as phenotype according to experimental evidence. " NGO0017 s__Neisseria gonorrhoeae folP - WP_003702942.1 - - ARO:3004873 p.194_195insSerGly Protein variant detected acquired - sulfonamide antibiotic nonwildtype R not applicable EUCAST v14.0 (2024) 7642493 "ECO:0001113 point mutation phenotypic evidence, ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence" weak "lacks evidence for this species, low clinical relevance" "Wild type gene encoding dihydropteroate synthase, mutation confers resistance to sulfonamides. Originally described in N. meningitidis and can be tracked in N. gonorrhoeae for surveillance purposes. No MIC data available for geno-pheno comparisons, NWT R assigned as phenotype according to experimental evidence. " NGO0018 s__Neisseria gonorrhoeae gyrA - WP_033785346.1 - - ARO:3003292 p.Ser91Phe Protein variant detected acquired ciprofloxacin - nonwildtype R MIC >0.06 mg/L EUCAST v14.0 (2024) "7830580, 11181352" "ECO:0005027 genetic transformation evidence, ECO:0001103 natural variation mutant evidence" strong "Wildtype core gene, not expected to confer drug resistance unless a S91F mutation is present." NGO0019 s__Neisseria gonorrhoeae gyrA - WP_033785346.1 - - ARO:3003292 p.Ser91Tyr Protein variant detected acquired ciprofloxacin - nonwildtype R MIC >0.06 mg/L EUCAST v14.0 (2024) "35453249, 33432328, 11181352" ECO:0001103 natural variation mutant evidence strong Mutation found when exposing WHO_F to increasing concentrations of ciprofloxacin. Found in natural populations in low proportions compared with S91F. NGO0020 s__Neisseria gonorrhoeae gyrA - WP_033785346.1 - - ARO:3003292 p.Asp95Ala Protein variant detected acquired ciprofloxacin - wildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "30961546, 30961546" ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with S91 mutations, so its individual effect on MIC is difficult to assess. In isolates with only this mutation, according to ECOFF and clinical breakpoints, the most frequent phenotype is WT S." NGO0021 s__Neisseria gonorrhoeae gyrA - WP_033785346.1 - - ARO:3003292 p.Asp95Asn Protein variant detected acquired ciprofloxacin - nonwildtype R MIC >0.06 mg/L EUCAST v14.0 (2024) "7830580, 11181352" "ECO:0005027 genetic transformation evidence, ECO:0001103 natural variation mutant evidence" moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with S91 mutations, so its individual effect on MIC is difficult to assess." NGO0022 s__Neisseria gonorrhoeae gyrA - WP_033785346.1 - - ARO:3003292 p.Asp95Gly Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "7830580, 11181352" "ECO:0005027 genetic transformation evidence, ECO:0001103 natural variation mutant evidence" moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with S91 mutations, so its individual effect on MIC is difficult to assess. In isolates with only this mutation, nearly the same number of isolates had a S/I vs R phenotype. With this information and also with the experimental evidence, a NWT S phenotype is indicated." NGO0023 s__Neisseria gonorrhoeae gyrB - WP_050171206.1 - - ARO:3004859 p.Asp429Asn Protein variant detected acquired Zoliflodacin - nonwildtype R not applicable not applicable "31730160, 38216602, 36868257" "ECO:0001113 point mutation phenotypic evidence, ECO:0005027 genetic transformation evidence" moderate unknown clinical relevance "This mutation was found in low frequency when exposing N. gonorrhoeae to zoliflodacin in vitro in PMID 31730160. It was also induced in commensal Neisseria spp and transfered via transformation to N. gonorrhoeae in 38216602. Can also arise through selection on ciprofloxacin in vitro (PMID 36868257), increasing ciprofloxacin MICs." NGO0024 s__Neisseria gonorrhoeae gyrB - WP_050171206.1 - - ARO:3004859 p.Lys450Asn Protein variant detected acquired Zoliflodacin - nonwildtype R not applicable not applicable "31730160, 38216602" "ECO:0001113 point mutation phenotypic evidence, ECO:0005027 genetic transformation evidence" moderate unknown clinical relevance This mutation was found in low frequency when exposing N. gonorrhoeae to zoliflodacin in vitro in PMID 31730160. It was also induced in commensal Neisseria spp and transfered via transformation to N. gonorrhoeae in 38216602. NGO0025 s__Neisseria gonorrhoeae gyrB - WP_050171206.1 - - ARO:3004859 p.Lys450Thr Protein variant detected acquired Zoliflodacin - nonwildtype R not applicable not applicable "31730160, 38216602" "ECO:0001113 point mutation phenotypic evidence, ECO:0005027 genetic transformation evidence" moderate unknown clinical relevance This mutation was found in low frequency when exposing N. gonorrhoeae to zoliflodacin in vitro in PMID 31730160. It was also induced in commensal Neisseria spp and transfered via transformation to N. gonorrhoeae in 38216602. NGO0026 s__Neisseria gonorrhoeae macAB - NZ_AP023073.1:147313-147537 - - ARO:3000533 c.[-48G>T] Promoter variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 16162665 ECO:0005027 genetic transformation evidence strong "lacks evidence of the degree to which MIC is affected, low clinical relevance" "In vitro evidence from PMID 16162665, very rare in clinical isolates." NGO0027 s__Neisseria gonorrhoeae mtrC - NZ_CP012026.1:1110850-1110550 - - ARO:3005004 c.[-120C>T] Promoter variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrC_C-120T. Same as mtrR_G-131A." NGO0028 s__Neisseria gonorrhoeae mtrC - NZ_CP012026.1:1110850-1110550 - - ARO:3005004 - Inactivating mutation detected acquired azithromycin - wildtype S MIC <=1 mg/L ECOFF (January 2024) "32807804, 9534233" "ECO:0000012 functional complementation evidence, ECO:0005027 genetic transformation evidence" strong "Loss-of function of mtrC increases susceptibility to azithromycin, beta-lactams, tetracyclines and ciprofloxacin. PMID 32807804 reports particularly strong effects for azithromycin. " NGO0029 s__Neisseria gonorrhoeae mtrC - NZ_CP012026.1:1110850-1110550 - - ARO:3005004 c.[-120C>T] Promoter variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrC_C-120T. Same as mtrR_G-131A." NGO0030 s__Neisseria gonorrhoeae mtrC - NZ_CP012026.1:1110850-1110550 - - ARO:3005004 c.[-120C>T] Promoter variant detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrC_C-120T. Same as mtrR_G-131A." NGO0031 s__Neisseria gonorrhoeae mtrD - WP_003695678.1 - - ARO:3000811 - Inactivating mutation detected acquired azithromycin - wildtype S MIC <=1 mg/L ECOFF (January 2024) 9534233 ECO:0005027 genetic transformation evidence moderate lacks evidence of the degree to which MIC is affected Small deletions in mtrD were linked to antimicrobial hypersusceptibility in PMID 9534233. Mutation not in the AMRfinderplus database. NGO0032 s__Neisseria gonorrhoeae mtrD - WP_003695678.1 - - ARO:3000811 p.Arg714Gly Protein variant detected acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) "32457251, 32843551" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence, ECO:0001103 natural variation mutant evidence, ECO:0001034 crystallography evidence" strong "This mutation decreases susceptibility to azithromycin, often found in mosaic mtrD. Mutation not in the AMRfinderplus database. NWT R phenotype assigned according to experimental evidence." NGO0033 s__Neisseria gonorrhoeae mtrD - WP_003695678.1 - - ARO:3000811 p.Lys823Glu Protein variant detected acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) "32457251, 32843551" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence, ECO:0001103 natural variation mutant evidence, ECO:0001034 crystallography evidence" strong "This mutation decreases susceptibility to azithromycin, often found in mosaic mtrD. Mutation not in the AMRfinderplus database. NWT R phenotype assigned according to experimental evidence." NGO0034 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3004851 p.Ala39Thr Protein variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Repressor of the MtrCDE efflux pump. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrR_A39T. In PMID 33875000, isolates with only this mutation have a wide ranges of MICs~0.015-16 mg/L, most of them below the ECOFF. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0035 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3004851 p.Gly45Asp Protein variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) "7773394, 18761689" ECO:0005027 genetic transformation evidence moderate low clinical relevance "Repressor of the MtrCDE efflux pump. Decreases susceptibility to azithromycin, cephalosporins and tetracycline when mutated. mtrR_G45D. In PMID 33875000, isolates with only this mutation had MIC ranges from ~0.03-4 mg/L, most of them below the ECOFF. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0036 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-53Adel] Promoter variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) "12270819, 12493797" ECO:0005027 genetic transformation evidence moderate lacks evidence of the degree to which MIC is affected "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. MICs indistinguishable from strains without this deletion in PMID 12493797. PMID 12270819 shows an effect in decreasing susceptibility to penicillin by transformation experiments. In geno-pheno comparisons, most isolates with only this deletion were WT S (n=6442/6655). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0037 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-56A>C] Promoter variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 39012901 ECO:0001103 natural variation mutant evidence weak "statistical geno/pheno evidence but no experimental evidence, unknown clinical relevance" "This mutation showed increased MICs of azithromycin in PMID 39012901, although other works only associate it with reduced susceptibility to penicillin and tetracycline. In PMID 33875000, isolates with only this mutation showed MIC values just below the ECOFF for azithromycin. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0038 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-131G>A] Promoter variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrR_G-131A. Same as mtrC_C-120T. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0039 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3004851 p.Ala39Thr Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Repressor of the MtrCDE efflux pump. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrR_A39T. In PMID 33875000, isolates with only this mutation have a wide ranges of MICs~0.015-16 mg/L, most of them below the ECOFF. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0040 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3004851 p.Gly45Asp Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) "7773394, 18761689" ECO:0005027 genetic transformation evidence moderate low clinical relevance "Repressor of the MtrCDE efflux pump. Decreases susceptibility to azithromycin, cephalosporins and tetracycline when mutated. mtrR_G45D. In PMID 33875000, isolates with only this mutation had MIC ranges from ~0.03-4 mg/L, most of them below the ECOFF. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0041 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3005004 - Inactivating mutation detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) "32807804, 9534233" "ECO:0000012 functional complementation evidence, ECO:0005027 genetic transformation evidence" strong "Loss-of function of mtrC increases susceptibility to azithromycin, beta-lactams, tetracyclines and ciprofloxacin. PMID 32807804 reports particularly strong effects for azithromycin. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0042 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-53Adel] Promoter variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) "12270819, 12493797" ECO:0005027 genetic transformation evidence moderate lacks evidence of the degree to which MIC is affected "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. MICs indistinguishable from strains without this deletion in PMID 12493797. PMID 12270819 shows an effect in decreasing susceptibility to penicillin by transformation experiments. In geno-pheno comparisons, most isolates with only this deletion were WT S (n=6442/6655). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0043 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-56A>C] Promoter variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) 39012901 ECO:0001103 natural variation mutant evidence weak "statistical geno/pheno evidence but no experimental evidence, unknown clinical relevance" "This mutation showed increased MICs of azithromycin in PMID 39012901, although other works only associate it with reduced susceptibility to penicillin and tetracycline. In PMID 33875000, isolates with only this mutation showed MIC values just below the ECOFF for azithromycin. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0044 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-131G>A] Promoter variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrR_G-131A. Same as mtrC_C-120T. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0045 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3004851 p.Ala39Thr Protein variant detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Repressor of the MtrCDE efflux pump. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrR_A39T. In PMID 33875000, isolates with only this mutation have a wide ranges of MICs~0.015-16 mg/L, most of them below the ECOFF. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0046 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3004851 p.Gly45Asp Protein variant detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) "7773394, 18761689" ECO:0005027 genetic transformation evidence moderate low clinical relevance "Repressor of the MtrCDE efflux pump. Decreases susceptibility to azithromycin, cephalosporins and tetracycline when mutated. mtrR_G45D. In PMID 33875000, isolates with only this mutation had MIC ranges from ~0.03-4 mg/L, most of them below the ECOFF. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0047 s__Neisseria gonorrhoeae mtrR mtrR WP_047924300.1 - - ARO:3005004 - Inactivating mutation detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) "32807804, 9534233" "ECO:0000012 functional complementation evidence, ECO:0005027 genetic transformation evidence" strong "Loss-of function of mtrC increases susceptibility to azithromycin, beta-lactams, tetracyclines and ciprofloxacin. PMID 32807804 reports particularly strong effects for azithromycin. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0048 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-53Adel] Promoter variant detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) "12270819, 12493797" ECO:0005027 genetic transformation evidence moderate lacks evidence of the degree to which MIC is affected "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. MICs indistinguishable from strains without this deletion in PMID 12493797. PMID 12270819 shows an effect in decreasing susceptibility to penicillin by transformation experiments. In geno-pheno comparisons, most isolates with only this deletion were WT S (n=6442/6655). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0049 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-56A>C] Promoter variant detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) 39012901 ECO:0001103 natural variation mutant evidence weak "statistical geno/pheno evidence but no experimental evidence, unknown clinical relevance" "This mutation showed increased MICs of azithromycin in PMID 39012901, although other works only associate it with reduced susceptibility to penicillin and tetracycline. In PMID 33875000, isolates with only this mutation showed MIC values just below the ECOFF for azithromycin. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0050 s__Neisseria gonorrhoeae mtrR mtrR NZ_CP043871.1:1392766-1393015 - - ARO:3004851 c.[-131G>A] Promoter variant detected acquired tetracycline - nonwildtype S MIC <=0.5 mg/L ECOFF (January 2024) 18761689 ECO:0005027 genetic transformation evidence moderate low clinical relevance "Promoter of mtrR. Decreases susceptibility to azithromycin, beta-lactams and tetracycline when mutated. mtrR_G-131A. Same as mtrC_C-120T. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0051 s__Neisseria gonorrhoeae norM - NZ_AP023073.1:1198657-1198990 - - ARO:3001327 c.[-104C>T] Promoter variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 12533487 ECO:0005027 genetic transformation evidence moderate "lacks evidence of the degree to which MIC is affected, low clinical relevance" "In vitro evidence from PMID 12533487, very rare in clinical isolates." NGO0052 s__Neisseria gonorrhoeae norM - NZ_AP023073.1:1198657-1198990 - - ARO:3001327 c.[-7A>G] Promoter variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 12533487 ECO:0005027 genetic transformation evidence moderate "lacks evidence of the degree to which MIC is affected, low clinical relevance" "In vitro evidence from PMID 12533487, very rare in clinical isolates." NGO0053 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Asp86Asn Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "11181352, 33875000" ECO:0001103 natural variation mutant evidence strong "This mutation was found when exposing susceptible strains to increasing concentrations of ciprofloxacin in strains with gyrA mutations (PMID 11181352). Mutation also found in isolation (without other mutations in gyrA or parC) in a low proportion with MICs~0.25 mg/L (PMID 33875000). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0054 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Asp86Gly Protein variant detected acquired ciprofloxacin - wildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 39004438 ECO:0001103 natural variation mutant evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" Found in only one isolate in a global screening of ~33k N. gonorrhoeae isolates (PMID 39004438). Not found alone in geno-pheno comparisons nor clear experimental evidence of this mutation increasing MIC. No experimental evidence to call this mutation NWT. NGO0055 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Ser87Ile Protein variant detected acquired ciprofloxacin - wildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "35369513, 33875000" ECO:0001103 natural variation mutant evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess. Likely acquired through recombination (PMID 35369513), found in Neisseria meningitidis (PMID 29233459). No experimental evidence to call this mutation NWT." NGO0056 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Ser87Asn Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 11181352 ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation was found when exposing susceptible strains to increasing concentrations of ciprofloxacin in strains with gyrA mutations (PMID 11181352). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0057 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Ser87Arg Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 11181352 ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation was found when exposing susceptible strains to increasing concentrations of ciprofloxacin in strains with gyrA mutations (PMID 11181352). Mutation also found in isolation (without other mutations in gyrA or parC) in isolates showing a wide range of MICs~0.003->32 mg/L (PMID 33875000). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0058 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Ser87Cys Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 36735316 ECO:0001103 natural variation mutant evidence weak unknown clinical relevance NWT phenotype assigned due to experimental evidence even though MIC values do not reach the ECOFF. NGO0059 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Ser88Pro Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "7830580, 11181352" "ECO:0005027 genetic transformation evidence, ECO:0001103 natural variation mutant evidence" moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess, but there is evidence from PMID 7830580 that it appears when increasing the concentration of ciprofloxacin. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0060 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Glu91Lys Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "7830580, 11181352" ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0061 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Glu91Gly Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 12529019 ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0062 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Glu91Gln Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) "12529019, 11181352" ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0063 s__Neisseria gonorrhoeae parC - WP_010951227.1 - - ARO:3003929 p.Glu91Ala Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 35369513 ECO:0001103 natural variation mutant evidence moderate lacks evidence of the degree to which MIC is affected "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess. Likely acquired through recombination (PMID 35369513). Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0064 s__Neisseria gonorrhoeae parE - WP_003691666.1 - - ARO:3003313 p.Gly410Val Protein variant detected acquired ciprofloxacin - nonwildtype S MIC <=0.03 mg/L EUCAST v14.0 (2024) 12529019 ECO:0001103 natural variation mutant evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" "This mutation tends to appear together with gyrA mutations, so its individual effect on MIC is difficult to assess. Although in pheno-geno comparisons most of the isolates with only this mutation are WT, an NWT phenotype assigned due to experimental evidence." NGO0065 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala311Val Protein variant detected acquired - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) 23587946 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin when introduced in a strain with a susceptible penA allele and shows an additive effect when introduced together with T316P and T483S (PMID 23587946)." NGO0066 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ile312Met Protein variant detected acquired - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin, especially in combination with V316T and G545S (PMID 16940068)." NGO0067 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Val316Thr Protein variant detected acquired - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin, especially in combination with I312M and G545S (PMID 16940068)." NGO0068 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Val316Pro Protein variant detected acquired - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) 23587946 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin when introduced in a strain with a susceptible penA allele and shows an additive effect when introduced together with A311V and T316P (PMID 23587946)." NGO0069 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.345_346insAsp Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "2120542, 33875000, 35544098" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" moderate low clinical relevance The insertion of an aspartate in this position (not any other amino acid) decreases susceptibility to penicillin (PMID 2120542). The presence of strains with only this mutation in penA has shown MIC levels ~0.02-8 mg/L of benzylpenicillin and mostly <=0.125 mg/L of ceftriaxone and cefixime in PMID 33875000. This mutation has the greatest impact on penicillin MICs after controlling for bla presence/absence and has high specificity for predicting penicillin susceptibility in PMID 35544098. NGO0070 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Thr483Ser Protein variant detected acquired - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) 23587946 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin when introduced in a strain with a susceptible penA allele and shows an additive effect when introduced together with A311V and T483S (PMID 23587946)." NGO0071 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala501Pro Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "22155830, 17591846" ECO:0005027 genetic transformation evidence moderate unknown clinical relevance There are reports of susceptible gonococcal isolates with penA A501 mutations (e.g. PMID 17591846). NGO0072 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala501Thr Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 17591846 ECO:0001113 point mutation phenotypic evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" There are reports of susceptible gonococcal isolates with penA A501 mutations (e.g. PMID 17591846). NGO0073 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala501Val Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "20704258, 17591846" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" moderate unknown clinical relevance There are reports of susceptible gonococcal isolates with penA A501 mutations (e.g. PMID 17591846). NGO0074 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ile312Met Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin, especially in combination with V316T and G545S (PMID 16940068)." NGO0075 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Val316Thr Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin, especially in combination with I312M and G545S (PMID 16940068)." NGO0076 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Val316Pro Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 23587946 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin when introduced in a strain with a susceptible penA allele and shows an additive effect when introduced together with A311V and T316P (PMID 23587946)." NGO0077 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.345_346insAsp Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) "2120542, 33875000, 35544098" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" moderate low clinical relevance The insertion of an aspartate in this position (not any other amino acid) decreases susceptibility to penicillin (PMID 2120542). The presence of strains with only this mutation in penA has shown MIC levels ~0.02-8 mg/L of benzylpenicillin and mostly <=0.125 mg/L of ceftriaxone and cefixime in PMID 33875000. The absence of this insertion has the greatest impact on penicillin MICs after controlling for bla presence/absence and has high specificity for predicting penicillin susceptibility in PMID 35544098. NGO0078 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Thr483Ser Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 23587946 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin when introduced in a strain with a susceptible penA allele and shows an additive effect when introduced together with A311V and T483S (PMID 23587946)." NGO0079 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala501Pro Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) "22155830, 17591846" ECO:0005027 genetic transformation evidence moderate unknown clinical relevance There are reports of susceptible gonococcal isolates with penA A501 mutations (e.g. PMID 17591846). NGO0080 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala501Thr Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 17591846 ECO:0001113 point mutation phenotypic evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" There are reports of susceptible gonococcal isolates with penA A501 mutations (e.g. PMID 17591846). NGO0081 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala501Val Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) "20704258, 17591846" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" moderate unknown clinical relevance There are reports of susceptible gonococcal isolates with penA A501 mutations (e.g. PMID 17591846). NGO0082 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Phe504Leu Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "20704258, 18986991" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence, ECO:0001034 crystallography evidence" strong "Reverting this mutation substantially reduced MIC of penicillin and had a minimal effect on cephalosporin MICs in PMID 20704258. This mutation has an effect on the structure of PBP2, specially in combination with P551L (PMID 18986991)." NGO0083 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala510Val Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "20704258, 18986991" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence, ECO:0001034 crystallography evidence" strong Reverting this mutation substantially reduced MIC of penicillin but not of cephalosporins in PMID 20704258. NGO0084 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Asn512Tyr Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 20704258 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "Reverting this mutation reduced MIC of ceftriaxone, cefixime and penicillin in PMID 20704258." NGO0085 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Ala516Gly Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 18986991 ECO:0001034 crystallography evidence strong This mutation has a minor effect in the structure of PBP2 (PMID 18986991). NGO0086 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Gly542Ser Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "32779717, 20511367" ECO:0001103 natural variation mutant evidence weak statistical geno/pheno evidence but no experimental evidence This mutation has been statistically associated with increased MICs of ceftriaxone and penicillin (e.g. PMID 20511367) but experimental evidence is not available. NGO0087 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Gly545Ser Protein variant detected acquired - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin, especially in combination with I312M and V316T (PMID 16940068)." NGO0088 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Gly542Ser Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) "32779717, 20511367" ECO:0001103 natural variation mutant evidence weak statistical geno/pheno evidence but no experimental evidence This mutation has been statistically associated with increased MICs of ceftriaxone and penicillin (e.g. PMID 20511367) but experimental evidence is not available. NGO0089 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Gly545Ser Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "This mutation significantly increases MIC to ceftriaxone, cefixime and penicillin, especially in combination with I312M and V316T (PMID 16940068)." NGO0090 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Pro551Leu Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "32779717, 20511367" ECO:0001103 natural variation mutant evidence weak statistical geno/pheno evidence but no experimental evidence This mutation has been statistically associated with increased MICs of ceftriaxone and penicillin (e.g. PMID 20511367) but experimental evidence is not available. NGO0091 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Pro551Ser Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) "18986991, 20511367" ECO:0001034 crystallography evidence strong "This mutation causes the largest effect in the structure of the C-terminal end of PBP2, specially in combination with F504L (PMID 18986991)." NGO0092 s__Neisseria gonorrhoeae penA - WP_003693546.1 - - ARO:3004832 p.Pro551Ser Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) "18986991, 20511367" ECO:0001034 crystallography evidence strong "This mutation causes the largest effect in the structure of the C-terminal end of PBP2, specially in combination with F504L (PMID 18986991)." NGO0093 s__Neisseria gonorrhoeae ponA - WP_003687357.1 - - ARO:3004833 p.Leu421Pro Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 11850260 ECO:0005027 genetic transformation evidence strong Reverting this mutation via transformation decreased MIC of penicillin in PMID 11850260. NGO0094 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Gly120Lys Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong This mutation increases MIC of penicillin and tetracycline (PMID 12183233). NGO0095 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Gly120Asp Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong This mutation showed a small increase of penicillin MIC and not tetracycline (PMID 12183233). NGO0096 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Gly120Pro Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" This mutation was validated in a double mutant with A121P in PMID 12183233. The individual effect of the mutation has not been assessed. NGO0097 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Gly120Arg Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" This mutation was validated in a double mutant with A121H in PMID 12183233. The individual effect of the mutation has not been assessed. NGO0098 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Ala121Asn Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" This mutation was validated in a double mutant with G120N in PMID 12183233. The individual effect of the mutation has not been assessed. NGO0099 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Ala121Asp Protein variant detected acquired benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "Validated by transformation individually, although the increase in MIC is not that high as in the double mutant G120D+A12D." NGO0100 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Ala121Gly Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 37294009 ECO:0001103 natural variation mutant evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance, statistical geno/pheno evidence but no experimental evidence" Mutation found in the gonococcal population (e.g. PMID 37294009). NGO0101 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Ala121Ser Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 37294009 ECO:0001103 natural variation mutant evidence weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance, statistical geno/pheno evidence but no experimental evidence" Mutation found in the gonococcal population (e.g. PMID 37294009). NGO0102 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Ala121His Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" This mutation was validated in a double mutant with G120R in PMID 12183233. The individual effect of the mutation has not been assessed. NGO0103 s__Neisseria gonorrhoeae porB1b - WP_106333382.1 - - ARO:3000464 p.Ala121Pro Protein variant detected acquired benzylpenicillin - nonwildtype S MIC <=0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" weak "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" This mutation was validated in a double mutant with G120P in PMID 12183233. The individual effect of the mutation has not been assessed. NGO0104 s__Neisseria gonorrhoeae rplD - WP_003690088.1 - - ARO:3004956 p.Gly70Asp Protein variant detected acquired azithromycin - nonwildtype S MIC <=1 mg/L ECOFF (January 2024) 33097713 ECO:0005027 genetic transformation evidence strong "Contributes to decreased susceptibility to azithromycin. In pheno-geno comparisons, most isolates with only this deletion were WT S (n=303/320), but a NWT phenotype is assigned because there is experimental evidence that this mutation increases MIC of azithromycin." NGO0105 s__Neisseria gonorrhoeae rplV - WP_002215424.1 - - - p.Lys83_89insLysLysGlyProSerLeuLys Protein variant detected acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 27638945 ECO:0001103 natural variation mutant evidence moderate "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" One isolate was found in PMID 27638945 with an MIC=16 mg/L. NGO0106 s__Neisseria gonorrhoeae rplV - WP_002215424.1 - - - p.Lys90_94LysAlaArgAlaLys Protein variant detected acquired azithromycin - nonwildtype R MIC >1 mg/L ECOFF (January 2024) 27638945 ECO:0001103 natural variation mutant evidence moderate "lacks evidence of the degree to which MIC is affected, unknown clinical relevance" One isolate was found in PMID 27638945 with an MIC=16 mg/L. NGO0107 s__Neisseria gonorrhoeae rpoB - WP_003690105.1 - - ARO:3003288 p.Pro157Leu Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 32011233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong The introduction of this mutation into a ceftriaxone-susceptible strain recapitulated the reduced susceptibility of the donor strain in PMID 32011233. NGO0108 s__Neisseria gonorrhoeae rpoB - WP_003690105.1 - - ARO:3003288 p.Gly158Val Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 32011233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong The introduction of this mutation into a ceftriaxone-susceptible strain recapitulated the reduced susceptibility of the donor strain in PMID 32011233. NGO0109 s__Neisseria gonorrhoeae rpoB - WP_003690105.1 - - ARO:3003288 p.Arg201His Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 32011233 ECO:0005027 genetic transformation evidence strong The introduction of this mutation into a ceftriaxone-susceptible strain recapitulated the reduced susceptibility of the donor strain in PMID 32011233. NGO0110 s__Neisseria gonorrhoeae rpoB - WP_003690105.1 - - ARO:3003288 p.His552Asn Protein variant detected acquired rifampin - nonwildtype R not applicable not applicable 14614066 ECO:0005027 genetic transformation evidence moderate lacks evidence for this species "The experimental evidence is in N. meningitidis, although increased MICs of rifampin have been found associated with this mutation in N. gonorrhoeae (e.g. three WHO reference strains, PMID 38889110). His553Asn in the AMRfinderplus database." NGO0111 s__Neisseria gonorrhoeae rpoD - WP_003688264.1 - - - p.92_95delAsp Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 32011233 ECO:0005027 genetic transformation evidence strong The introduction of this mutation into a ceftriaxone-susceptible strain recapitulated the reduced susceptibility of the donor strain in PMID 32011233. NGO0112 s__Neisseria gonorrhoeae rpoD - WP_003688264.1 - - - p.Glu98Lys Protein variant detected acquired - cephalosporin nonwildtype S MIC <=0.125 mg/L EUCAST v14.0 (2024) 32011233 ECO:0005027 genetic transformation evidence strong The introduction of this mutation into a ceftriaxone-susceptible strain recapitulated the reduced susceptibility of the donor strain in PMID 32011233. NGO0113 s__Neisseria gonorrhoeae rpsE - WP_002215445.1 - - ARO:3007526 p.Thr24Pro Protein variant detected acquired spectinomycin - nonwildtype R MIC >64 mg/L EUCAST v14.0 (2024) 23183436 ECO:0005027 genetic transformation evidence strong Confers low level resistance to spectinomycin. Not enough data to evaluate phenotype codification from geno-pheno data. NWT R assigned according to experimental evidence. NGO0114 s__Neisseria gonorrhoeae rpsE - WP_002215445.1 - - ARO:3007526 p.27_28delVal Protein variant detected acquired spectinomycin - nonwildtype R MIC >64 mg/L EUCAST v14.0 (2024) 23183436 ECO:0005027 genetic transformation evidence moderate lacks evidence of the degree to which MIC is affected rpsE mutations in codon 27 and 28 are very close to each other and the individual effects are difficult to assess. V27del+K28E conferred high-level spectinomycin resistance in an isolate from Norway (PMID 23183436). NGO0115 s__Neisseria gonorrhoeae rpsE - WP_002215445.1 - - ARO:3007526 p.Lys28Glu Protein variant detected acquired spectinomycin - nonwildtype R MIC >64 mg/L EUCAST v14.0 (2024) 23183436 ECO:0005027 genetic transformation evidence moderate lacks evidence of the degree to which MIC is affected rpsE mutations in codon 27 and 28 are very close to each other and the individual effects are difficult to assess. V27del+K28E conferred high-level spectinomycin resistance in an isolate from Norway (PMID 23183436). NGO0116 s__Neisseria gonorrhoeae rpsJ - WP_002215394.1 - - ARO:3003930 p.Val57Met Protein variant detected acquired tetracycline - nonwildtype R MIC >0.5 mg/L EUCAST v14.0 (2024) 16189114 "ECO:0001113 point mutation phenotypic evidence, ECO:0005027 genetic transformation evidence" strong This mutation causes intermediate resistance to tetracycline in N. gonorrhoeae. NGO0117 s__Neisseria gonorrhoeae rpsJ - WP_002215394.1 - - ARO:3003930 p.Val57Leu Protein variant detected acquired tetracycline - nonwildtype R MIC >0.5 mg/L EUCAST v14.0 (2024) 16189114 "ECO:0001113 point mutation phenotypic evidence, ECO:0005027 genetic transformation evidence" strong This mutation causes the same level of resistance to tetracycline than V57M. NGO0118 s__Neisseria gonorrhoeae rpsJ - WP_002215394.1 - - ARO:3003930 p.Val57Gln Protein variant detected acquired tetracycline - nonwildtype R MIC >0.5 mg/L EUCAST v14.0 (2024) 16189114 "ECO:0001113 point mutation phenotypic evidence, ECO:0005027 genetic transformation evidence" strong This mutation causes the same level of resistance to tetracycline than V57M. NGO0119 s__Neisseria gonorrhoeae tet(M) tet(M) WP_063856403.1 - - ARO:3000186 - Gene presence detected acquired tetracycline - nonwildtype R MIC >0.5 mg/L EUCAST v14.0 (2024) 3099640 ECO:0005027 genetic transformation evidence strong The presence of this gene on the conjugative plasmid causes high-level tetracycline resistance. NGO0120 s__Neisseria gonorrhoeae NGO0065 & NGO0066 & (NGO0067 | NGO0068) & NGO0070 & NGO0087 - - - - - - Combination - - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) "16940068, 20704258, 23587946" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "penA mosaic (A311V, I312M, V316P/T, T483S and G545S)" NGO0121 s__Neisseria gonorrhoeae NGO0065 & NGO0066 & NGO0087 - - - - - - Combination - - cephalosporin nonwildtype R MIC >0.125 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "penA mosaic (I312M, V316T, G545S)" NGO0122 s__Neisseria gonorrhoeae NGO0065 & NGO0066 & NGO0087 - - - - - - Combination - benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) "16940068, 20704258" "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong "penA mosaic (I312M, V316T, G545S)" NGO0123 s__Neisseria gonorrhoeae NGO0094 & NGO0098 - - - - - - Combination - benzylpenicillin - nonwildtype I MIC >0.06 mg/L EUCAST v14.0 (2024) 12183233 "ECO:0005027 genetic transformation evidence, ECO:0001113 point mutation phenotypic evidence" strong The effect in increasing MIC to penicillin and tetracycline is higher in the double mutant porB G120K A121N (PMID 12183233).