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
EFC0001	s__Enterococcus faecalis	pbp4	-	WP_070676928.1	-	-	-	-	Gene presence detected	core	ceftriaxone	-	wildtype	R	not applicable	not applicable	"32041714, 14973044"	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"The native pbp5 sequence in E. faecalis is responsible for intrinsic cephalosporin resistance, mutations in this protein are known to alter beta-lactam resistance profiles, e.g. increase resistance to ampicillin. In Enterococcus faecalis, class B PBP5 mediates intrinsic resistance to the cephalosporin class of _-lactam antibiotics. According to 32041714, ""As expected (15), the _pbp5 mutant exhibited a substantial loss of resistance to cephalosporins, including representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins (cefuroxime, ceftriaxone, cefepime, and ceftaroline, respectively; Table 1)."" 14973044: ""E. faecalis JH2-2 was highly resistant to the expanded-spectrum cephalosporin ceftriaxone, and deletion of pbp5 led to a 4,000-fold reduction in the MIC of this drug (Table 2). [...] The pbp5 gene of E. faecalis JH2-2 cloned under the control of the aphA-3p promoter of the shuttle vector pNJ2 (Fig. 1B) restored wild-type _-lactam resistance in JH2-2 _pbp5."""
EFC0002	s__Enterococcus faecalis	pbp4	-	WP_070676928.1	-	-	-	-	Gene presence detected	core	cefuroxime	-	wildtype	R	not applicable	not applicable	"32041714, 14973044"	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"The native pbp5 sequence in E. faecalis is responsible for intrinsic cephalosporin resistance, mutations in this protein are known to alter beta-lactam resistance profiles, e.g. increase resistance to ampicillin. In Enterococcus faecalis, class B PBP5 mediates intrinsic resistance to the cephalosporin class of _-lactam antibiotics. According to 32041714, ""As expected (15), the _pbp5 mutant exhibited a substantial loss of resistance to cephalosporins, including representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins (cefuroxime, ceftriaxone, cefepime, and ceftaroline, respectively; Table 1)."" 14973044: ""E. faecalis JH2-2 was highly resistant to the expanded-spectrum cephalosporin ceftriaxone, and deletion of pbp5 led to a 4,000-fold reduction in the MIC of this drug (Table 2). [...] The pbp5 gene of E. faecalis JH2-2 cloned under the control of the aphA-3p promoter of the shuttle vector pNJ2 (Fig. 1B) restored wild-type _-lactam resistance in JH2-2 _pbp5."""
EFC0003	s__Enterococcus faecalis	pbp4	-	WP_070676928.1	-	-	-	-	Gene presence detected	core	cefepime	-	wildtype	R	not applicable	not applicable	"32041714, 14973044"	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"The native pbp5 sequence in E. faecalis is responsible for intrinsic cephalosporin resistance, mutations in this protein are known to alter beta-lactam resistance profiles, e.g. increase resistance to ampicillin. In Enterococcus faecalis, class B PBP5 mediates intrinsic resistance to the cephalosporin class of _-lactam antibiotics. According to 32041714, ""As expected (15), the _pbp5 mutant exhibited a substantial loss of resistance to cephalosporins, including representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins (cefuroxime, ceftriaxone, cefepime, and ceftaroline, respectively; Table 1)."" 14973044: ""E. faecalis JH2-2 was highly resistant to the expanded-spectrum cephalosporin ceftriaxone, and deletion of pbp5 led to a 4,000-fold reduction in the MIC of this drug (Table 2). [...] The pbp5 gene of E. faecalis JH2-2 cloned under the control of the aphA-3p promoter of the shuttle vector pNJ2 (Fig. 1B) restored wild-type _-lactam resistance in JH2-2 _pbp5."""
EFC0004	s__Enterococcus faecalis	pbp4	-	WP_070676928.1	-	-	-	-	Gene presence detected	core	ceftaroline	-	wildtype	R	not applicable	not applicable	"32041714, 14973044"	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"The native pbp5 sequence in E. faecalis is responsible for intrinsic cephalosporin resistance, mutations in this protein are known to alter beta-lactam resistance profiles, e.g. increase resistance to ampicillin. In Enterococcus faecalis, class B PBP5 mediates intrinsic resistance to the cephalosporin class of _-lactam antibiotics. According to 32041714, ""As expected (15), the _pbp5 mutant exhibited a substantial loss of resistance to cephalosporins, including representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins (cefuroxime, ceftriaxone, cefepime, and ceftaroline, respectively; Table 1)."" 14973044: ""E. faecalis JH2-2 was highly resistant to the expanded-spectrum cephalosporin ceftriaxone, and deletion of pbp5 led to a 4,000-fold reduction in the MIC of this drug (Table 2). [...] The pbp5 gene of E. faecalis JH2-2 cloned under the control of the aphA-3p promoter of the shuttle vector pNJ2 (Fig. 1B) restored wild-type _-lactam resistance in JH2-2 _pbp5."""
EFC0005	s__Enterococcus faecalis	pbpA	-	-	AEA94845.1	-	-	-	Gene presence detected	core	ceftriaxone	-	wildtype	R	not applicable	not applicable	32041714	ECO:0001091 knockout phenotypic evidence	strong		"32041714: ""Analysis of the _pbpA mutants from both lineages of E. faecalis revealed a substantial loss of resistance to representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins, similar to the phenotype of the _pbp5 mutant, that was complemented by ectopic expression of pbpA (Table 1). Immunoblotting verified that the defect of the _pbpA mutant is not due to loss of Pbp5(4) expression in the _pbpA mutant (Fig. S4), indicating that both bPBPs are therefore required for enterococcal cephalosporin resistance. As with the _pbp5 mutant, the defects of the _pbpA mutant were largely specific to cephalosporins, as no changes in resistance were observed for ampicillin, bacitracin, or gentamicin."""
EFC0006	s__Enterococcus faecalis	pbpA	-	-	AEA94845.1	-	-	-	Gene presence detected	core	cefuroxime	-	wildtype	R	not applicable	not applicable	32041714	ECO:0001091 knockout phenotypic evidence	strong		"32041714: ""Analysis of the _pbpA mutants from both lineages of E. faecalis revealed a substantial loss of resistance to representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins, similar to the phenotype of the _pbp5 mutant, that was complemented by ectopic expression of pbpA (Table 1). Immunoblotting verified that the defect of the _pbpA mutant is not due to loss of Pbp5(4) expression in the _pbpA mutant (Fig. S4), indicating that both bPBPs are therefore required for enterococcal cephalosporin resistance. As with the _pbp5 mutant, the defects of the _pbpA mutant were largely specific to cephalosporins, as no changes in resistance were observed for ampicillin, bacitracin, or gentamicin."""
EFC0007	s__Enterococcus faecalis	pbpA	-	-	AEA94845.1	-	-	-	Gene presence detected	core	cefepime	-	wildtype	R	not applicable	not applicable	32041714	ECO:0001091 knockout phenotypic evidence	strong		"32041714: ""Analysis of the _pbpA mutants from both lineages of E. faecalis revealed a substantial loss of resistance to representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins, similar to the phenotype of the _pbp5 mutant, that was complemented by ectopic expression of pbpA (Table 1). Immunoblotting verified that the defect of the _pbpA mutant is not due to loss of Pbp5(4) expression in the _pbpA mutant (Fig. S4), indicating that both bPBPs are therefore required for enterococcal cephalosporin resistance. As with the _pbp5 mutant, the defects of the _pbpA mutant were largely specific to cephalosporins, as no changes in resistance were observed for ampicillin, bacitracin, or gentamicin."""
EFC0008	s__Enterococcus faecalis	pbpA	-	-	AEA94845.1	-	-	-	Gene presence detected	core	ceftaroline	-	wildtype	R	not applicable	not applicable	32041714	ECO:0001091 knockout phenotypic evidence	strong		"32041714: ""Analysis of the _pbpA mutants from both lineages of E. faecalis revealed a substantial loss of resistance to representative 2nd-, 3rd-, 4th-, and 5th-generation cephalosporins, similar to the phenotype of the _pbp5 mutant, that was complemented by ectopic expression of pbpA (Table 1). Immunoblotting verified that the defect of the _pbpA mutant is not due to loss of Pbp5(4) expression in the _pbpA mutant (Fig. S4), indicating that both bPBPs are therefore required for enterococcal cephalosporin resistance. As with the _pbp5 mutant, the defects of the _pbpA mutant were largely specific to cephalosporins, as no changes in resistance were observed for ampicillin, bacitracin, or gentamicin."""
EFC0009	s__Enterococcus faecalis	pbpF	-	-	AAO80501.1	-	-	-	Gene presence detected	core	ceftriaxone	-	wildtype	R	not applicable	not applicable	19304851	ECO:0001091 knockout phenotypic evidence	strong		"Pbp5 is the main determinant of cephalosporin resistance in E. faecalis but it needs to cooperate with the glycosyltransferase domain of specific class A PBPs (PbpF or PonA) for peptidoglycan polymerization in the presence of cephalosporins (i.e. resistance phenotype). 14973044: ""Single deletion of any of the three class A PBP genes of E. faecalis (ponA, pbpF, or pbpZ) had no impact on the MICs of _-lactam antibiotics (Table 2). Among the three combinations of double deletions, only the deletion of ponA and pbpF resulted in a large decrease (1,000-fold) in ceftriaxone resistance. Thus, either ponA or pbpF was required for intrinsic ceftriaxone resistance mediated by PBP5."""
EFC0010	s__Enterococcus faecalis	ponA	-	-	AAO80948.1	-	-	-	Gene presence detected	core	ceftriaxone	-	wildtype	R	not applicable	not applicable	19304851	ECO:0001091 knockout phenotypic evidence	strong		"Pbp5 is the main determinant of cephalosporin resistance in E. faecalis but it needs to cooperate with the glycosyltransferase domain of specific class A PBPs (PbpF or PonA) for peptidoglycan polymerization in the presence of cephalosporins (i.e. resistance phenotype). 14973044: ""Single deletion of any of the three class A PBP genes of E. faecalis (ponA, pbpF, or pbpZ) had no impact on the MICs of _-lactam antibiotics (Table 2). Among the three combinations of double deletions, only the deletion of ponA and pbpF resulted in a large decrease (1,000-fold) in ceftriaxone resistance. Thus, either ponA or pbpF was required for intrinsic ceftriaxone resistance mediated by PBP5."""
EFC0011	s__Enterococcus faecalis	IreK	-	-	AAO82800.1	-	ARO:3007678 	-	Gene presence detected	core	ceftriaxone	-	wildtype	R	not applicable	not applicable	34672600	ECO:0001091 knockout phenotypic evidence	strong		"34672600: The absence of IreK leads to cell envelope defects and increased susceptibility to a variety of cephalosporins, including ceftriaxone (21,23,24). Increased IreK phosphorylation in response to ceftriaxone treatment has been shown to correlate with antimicrobial resistance, (21) and three conserved sites on the activation loop (T163, T166, and T168) are essential for IreK autophosphorylation and activation, and increase antibiotic resistance when phosphorylated. "
EFC0012	s__Enterococcus faecalis	lsa(A)	lsa(A)	WP_002365053.1	AY225127.1	-	ARO:3000300	-	Gene presence detected	core	clindamycin	-	wildtype	R	not applicable	not applicable	12019099	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"12019099: ""Disruption of lsa(A) gene of E. faecalis was associated with a > or =40-fold decrease in MICs of Q-D (to 0.75 microg/ml), CLI (to 0.12 to 0.5 microg/ml), and dalfopristin (DAL) (to 4 to 8 microg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 microg/ml; CLI MIC, 32 to 48 microg/ml; DAL MIC, 512 microg/ml). Complementation of the disruption mutant with lsa on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels."""
EFC0013	s__Enterococcus faecalis	lsa(A)	lsa(A)	WP_002365053.1	AY225127.1	-	ARO:3000300	-	Gene presence detected	core	dalfopristin	-	wildtype	R	not applicable	not applicable	12019099	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"12019099: ""Disruption of lsa(A) gene of E. faecalis was associated with a > or =40-fold decrease in MICs of Q-D (to 0.75 microg/ml), CLI (to 0.12 to 0.5 microg/ml), and dalfopristin (DAL) (to 4 to 8 microg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 microg/ml; CLI MIC, 32 to 48 microg/ml; DAL MIC, 512 microg/ml). Complementation of the disruption mutant with lsa on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels."""
EFC0014	s__Enterococcus faecalis	lsa(A)	lsa(A)	WP_002365053.1	AY225127.1	-	ARO:3000300	-	Gene presence detected	core	quinupristin-dalfopristin	-	wildtype	R	not applicable	not applicable	12019099	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"12019099: ""Disruption of lsa(A) gene of E. faecalis was associated with a > or =40-fold decrease in MICs of Q-D (to 0.75 microg/ml), CLI (to 0.12 to 0.5 microg/ml), and dalfopristin (DAL) (to 4 to 8 microg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 microg/ml; CLI MIC, 32 to 48 microg/ml; DAL MIC, 512 microg/ml). Complementation of the disruption mutant with lsa on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels."""
EFC0015	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	ciprofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0016	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	ciprofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0017	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	norfloxacin	-	wildtype	S	MIC <=8 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0018	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	norfloxacin	-	wildtype	S	MIC <=8 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0019	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	ofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0020	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	ofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0021	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	gentamicin	-	wildtype	S	MIC <=64 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0022	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	gentamicin	-	wildtype	S	MIC <=64 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0023	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	minocycline	-	wildtype	S	MIC <=0.5 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0024	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	minocycline	-	wildtype	S	MIC <=0.5 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0025	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	tetracycline 	-	wildtype	S	MIC <=4 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0026	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	tetracycline 	-	wildtype	S	MIC <=4 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0027	s__Enterococcus faecalis	efrA	-	-	HG970098.1	-	ARO:3003948	-	Gene presence detected	core	rifampin	-	wildtype	S	MIC <=8 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0028	s__Enterococcus faecalis	efrB	-	-	HG970103.1	-	ARO:3003949	-	Gene presence detected	core	rifampin	-	wildtype	S	MIC <=8 mg/L	ECOFF	"14638474, 25084670, 27381387"	"ECO:0001091 knockout phenotypic evidence, ECO:0000154 heterologous protein expression evidence"	strong		"Originally, the evidence for the role of efrAB genes in antibiotic resistance in E. faecalis came from heterologous expression of these genes in a hypersensitive E. coli strain (PMID: 14638474), resulting in increased resistance to multiple antibiotics (including norfloxacin, ciprofloxacin, and doxycycline), and by the chemical inhibition if this efflux pump by EDTA resulting in reduced MIC to multiple antibiotics (PMID: 14638474), variable MIC fold reduction depending on strain and antibiotic, see Table 3 in paper. Later, 27381387 provided stronger evidence with a efrAB knockout mutant: ""Unexpectedly, E. faecalis 4205 _efrAB had a much less pronounced phenotype than E. faecalis 4205 _efrCD, exhibiting only 2-fold-reduced resistance to acriflavine and ethidium [and not affecting the MIC of clinically used antibiotics, see Table 1]."" efrAB knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0029	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	ciprofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0030	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	ciprofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0031	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	norfloxacin	-	wildtype	S	MIC <=8 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0032	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	norfloxacin	-	wildtype	S	MIC <=8 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0033	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	ofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0034	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	ofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0035	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	gentamicin	-	wildtype	S	MIC <=64 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0036	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	gentamicin	-	wildtype	S	MIC <=64 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0037	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	minocycline	-	wildtype	S	MIC <=0.5 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0038	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	minocycline	-	wildtype	S	MIC <=0.5 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0039	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	tetracycline 	-	wildtype	S	MIC <=4 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0040	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	tetracycline 	-	wildtype	S	MIC <=4 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0041	s__Enterococcus faecalis	efrC	-	-	AAO80603.1	-	-	-	Gene presence detected	core	rifampin	-	wildtype	S	MIC <=8 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains"
EFC0042	s__Enterococcus faecalis	efrD	-	-	AAO80604.1	-	-	-	Gene presence detected	core	rifampin	-	wildtype	S	MIC <=8 mg/L	ECOFF	27381387	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"27381387: Deletion of EfrCD on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342 but not to clinically used antibiotics tested including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains (see Table 1). efrCD knockout evidence shows that this efflux pump does not contribute to resistance to antibiotics tested (including ciprofloxacin, norfloxacin, ofloxacin, gentamicin, kanamycin, minocycline, tetracycline, rifampin) in two different strains."
EFC0043	s__Enterococcus faecalis	emeA	-	-	AB091338.1	-	ARO:3003551	-	Gene presence detected	core	norfloxacin	-	wildtype	S	MIC <=8 mg/L	ECOFF	"11709342, 11321571"	"ECO:0001091 knockout phenotypic evidence, ECO:0000012 functional complementation evidence"	strong		"11709342: ""EmeA seems to have a modest but consistent effect on the susceptibility of E. faecalis to diverse compounds such as norfloxacin and EtBr."" 11321571: “In E. faecalis, the ∆norA strain was only 2 to 3-fold more susceptible to norfloxacin (Figure 2A) and it showed little increased sensitivity to ciprofloxacin.” Because of modest effect of EmeA on norfloxacin resistance (see 11709342), and because E. faecalis is not intrinsically resistance to fluoroquinolones, the phenotypic effect chosen is ""S"""
EFC0044	s__Enterococcus faecalis	emeA	-	-	AB091338.1	-	ARO:3003551	-	Gene presence detected	core	ciprofloxacin	-	wildtype	S	MIC <=4 mg/L	ECOFF	11321571	ECO:0001091 knockout phenotypic evidence	strong		"11321571: “In E. faecalis, the ∆norA strain was only 2 to 3-fold more susceptible to norfloxacin (Figure 2A) and it showed little increased sensitivity to ciprofloxacin.” Because of modest effect of EmeA on ciprofloxacin resistance (according to 11321571), and because E. faecalis is not intrinsically resistance to fluoroquinolones, the phenotypic effect chosen is ""S"""
EFC0045	s__Enterococcus faecalis	dfrE	dfrE	-	AF028811.1	NF040541.1	ARO:3002875	-	Gene presence detected	core	trimethoprim	-	wildtype	S	not available	ECOFF ID	9869579	ECO:0000154 heterologous protein expression evidence	weak	lacks evidence for this species	"dfrE is a chromosome-encoded dihydrofolate reductase found in Enterococcus faecalis. According to 9869579: “The dfrE gene that caused resistance in E. coli when it was cloned into a multicopy plasmid is believed to code for an intrinsic E. faecalis DHFR because it was found in all E. faecalis isolates studied, despite their level of susceptibility to trimethoprim.“ dfrE chromosomal gene on its own does not confer resistance to trimethoprim in E. faecalis, as E. faecalis is not intrinsically resistant to trimethoprim. Also, only evidence of heterologous expression of this gene in E. coli exist, no knockout evidence could be found."