Erratum: Acquired antibiotic resistance genes: an overview.

A commentary on

Acquired antibiotic resistance genes: an overview

by van Hoek, A. H. A. M., Mevius, D., Guerra, B., Mullany, P., Roberts, A. P., and Aarts, H. J. M. (2011). Front. Microbio. 2:203. doi: 10.3389/fmicb.2011.00203

Dr. Marilyn C. Roberts and Dr. Stefan Schwarz have contacted the authors of the original publication with several comments and suggestions to better harmonize the correct nomenclature of the antibiotic resistance genes, as the gene names were not always correctly presented in the various tables given.

Authors often pick their own gene names which in many cases have been approved for use for other genetically distinct genes or give names to determinants which were already given an approved designated name. Therefore, we (Dr. Marilyn C. Roberts and Dr. Stefan Schwarz and Dr. Henk J. M. Aarts on behalf of the authors of the original publication) would like to present here the correct nomenclature and mechanistic features of the antibiotic resistance genes belonging to the following classes: Aminoglycosides (Table 1), Phenicols (Table 3), Macrolides–Lincosamides–Streptogramin B (Table 4), Quinolones (Table 5), Tetracyclines (Table 6), and Trimethoprim (Table 7). In addition some additional information is given on the various classes of antibiotic resistance genes as also a section regarding the antibiotic class Oxazolidinones has been added. Table 2 was correctly displayed by van Hoek et al. (2011) but has been updated.

Table 1

Acquired aminoglycoside resistance genes.

Mechanism	Gene name	Length (nt)	Accession number or reference	Coding region	Genera
ACT	aac(2′)-Ia	537	L06156	264… 800	Providencia
	aac(2′)-Ib	588	U41471	265… 852	Mycobacterium
	aac(2′)-Ic	546	U72714	373… 918	Mycobacterium
	aac(2′)-Id	633	U72743	386… 1018	Mycobacterium
	aac(2′)-Ie	549	NC_011896	3039059… 3039607	Mycobacterium
	aac(3)-I	465	AJ877225	5293… 5757	Pseudomonas
	aac(3)-Ia	534	X15852	1250… 1783	Acinetobacter, Escherichia, Klebsiella, Salmonella, Serratia, Streptomyces
	aac(3)-Ib	531	L06157	555… 1085	Pseudomonas
	aac(3)-Ib-aac(6′)-Ib	1005	AF355189	1435… 2439	Pseudomonas
	aac(3)-Ic	471	AJ511268	1295… 1765	Pseudomonas
	aac(3)-Id	477	AB114632	104… 580	Proteus, Pseudomonas, Salmonella, Vibrio
	aac(3)-Ie	477	AY463797	8583… 9059	Proteus, Pseudomonas, Salmonella, Vibrio
	aac(3)-If	465	AY884051	61… 525	Serratia, Pseudomonas
	aac(3)-Ig	477	CP000282	2333620… 2334096	Saccharophagus
	aac(3)-Ih	459	CP000490	509912… 510370	Paracoccus
	aac(3)-Ii	459	CP000356	638262… 638720	Sphingopyxis
	aac(3)-Ij	465	CP000155	6963012… 6963476	Hahella
	aac(3)-Ik	444	BX571856	765853… 766296	Staphylococcus
	aac(3)-IIa	861	X51534	91… 951	Acinetobacter, Enterobacter, Escherichia, Klebsiella, Pseudomonas, Salmonella
	aac(3)-IIb	810	M97172	656… 1465	Serratia
	aac(3)-IIc	861	X54723	819… 1679	Escherichia
	aac(3)-IId	861	EU022314	1… 861	Escherichia
	aac(3)-IIe	861	EU022315	1… 861	Escherichia
	aac(3)-IIIa	816	X55652	1124… 1939	Pseudomonas
	aac(3)-IIIb	738	L06160	984… 1721	Pseudomonas
	aac(3)-IIIc	840	L06161	106… 945	Pseudomonas
	aac(3)-IVa	786	X01385	244… 1029	Escherichia
	aac(3)-Va;
	see aac(3)-IIa
	aac(3)-Vb;
	see aac(3)-IIb
	aac(3)-VIa	900	M88012	193… 1092	Enterobacter, Escherichia, Salmonella
	aac(3)-VIIa	867	M22999	493… 1359	Streptomyces
	aac(3)-VIIIa	861	M55426	466… 1326	Streptomyces
	aac(3)-IXa	846	M55427	274… 1119	Micromonospora
	aac(3)-Xa	855	AB028210	2711… 3565	Streptomyces
	aac(6′)	441	AY553333	1392… 1832	Pseudomonas
	aac	555	AJ628983	1985… 2539	Pseudomonas
	aac(6′)	402	DQ302723	81… 482	Pseudomonas
	aac(6′)	555	EU912537	2092… 2646	Pseudomonas
	aac(6′)-Ia	558	M18967	757… 1314	Citrobacter, Escherichia, Klebsiella, Shigella
	aac(6′)-Ib	606	M21682	380… 985	Klebsiella, Proteus, Pseudomonas
	aac(6′)-Ib-cr	519	EF636461	1124… 1642	Enterobacter, Escherichia, Klebsiella, Pseudomonas, Salmonella
	aac(6′)-Ic	441	M94066	1554… 1994	Serratia
	aac(6′)-Id	450	X12618	905… 1354	Klebsiella
	aac(6′)-Ie;
	see aac(6′)-aph(2″)
	aac(6′)-If	435	X55353	279… 713	Enterobacter
	aac(6′)-Ig	438	L09246	544… 981	Acinetobacter
	aac(6′)-Ih	441	L29044	352… 792	Acinetobacter
	aac(6′)-Ii	549	L12710	169… 717	Enterococcus
	aac(6′)-Ij	441	L29045	260… 700	Acinetobacter
	aac(6′)-Ik	438	L29510	369… 806	Acinetobacter
	aac(6′)-Il	522	Z54241	530… 1051	Acinetobacter, Citrobacter
	aac(6′)-Im	537	AF337947	1215… 1751	Escherichia
	aac(6′)-In	573	Wu et al., 1997	–	Citrobacter
	aac(6′)-Iq	552	AF047556	127… 678	Klebsiella, Salmonella
	aac(6′)-Ir	441	AF031326	1… 441	Acinetobacter
	aac(6′)-Is	441	AF031327	1… 441	Acinetobacter
	aac(6′)-It	441	AF031328	1… 441	Acinetobacter
	aac(6′)-Iu	441	AF031329	1… 441	Acinetobacter
	aac(6′)-Iv	441	AF031330	1… 441	Acinetobacter
	aac(6′)-Iw	441	AF031331	1… 441	Acinetobacter
	aac(6′)-Ix	441	AF031332	1… 441	Acinetobacter
	aac(6′)-Iy	438	AF144880	3452… 3979	Salmonella
	aac(6′)-Iz	462	AF140221	390… 851	Stenotrophomonas
	aac(6′)-Iaa	438	NC_003197	1707358… 1707795	Salmonella
	aac(6′)-Iad	435	AB119105	1… 435	Acinetobacter
	aac(6′)-Iae	552	AB104852	1935… 2486	Pseudomonas, Salmonella
	aac(6′)-Iaf	552	AB462903	1200… 1751	Pseudomonas
	aac(6′)-Iai	567	EU886977	544… 1110	Pseudomonas
	aac(6′)-I30	555	AY289608	1524… 2078	Salmonella
	aac(6′)-31	519	AJ640197	2474… 2992	Acinetobacter
	aac(6′)-32	555	EF614235	2247… 2801	Pseudomonas
	aac(6′)-33	555	GQ337064	1203… 1757	Pseudomonas
	aac(6′)-IIa	555	M29695	707… 1261	Aeromonas, Klebsiella, Pseudomonas, Salmonella
	aac(6′)-IIb	543	L06163	532… 1074	Pseudomonas
	aac(6′)-IIc	582	AF162771	62… 643	Enterobacter, Klebsiella, Pseudomonas
	aac(6′)-Iid;
	see ant(3″)-Ih- aac(6′)-IId
	aac(6′)-III;
	see aac(6′)-Ic
	aac(6′)-IV	435	X55353	279… 713	Enterobacter
	aacA29	381	AY139599	768… 1148	Unknown
	aacA43	564	HQ247816	639… 1202	Klebsiella
	apmA	822	FN806789	2858… 3682	Staphylococcus
	sat2a	525	X51546	518… 1042	Acinetobacter, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Shigella, Vibrio
	sat3a	543	Z48231	221… 763	Escherichia
	sat4a	543	X92945	38870… 39412	Campylobacter, Enterococcus, Staphylococcus,Streptococcus
	aac(6′)-aph(2″)	1440	M13771	304… 1743	Enterococcus, Lactobacillus, Staphylococcus,Streptococcus
ACT–PHT	aph(2″-Ia; see
	aac(6′)-aph(2″)
MET	armA	774	AY220558	1978… 2751	Acinetobacter, Citrobacter, Enterobacter, Escherichia, Klebsiella, Salmonella, Serratia
	npmA	660	AB261016	3069… 3728	Escherichia
	rmtA	756	AB120321	6677… 7432	Pseudomonas
	rmtB	756	AB103506	1410… 2165	Enterobacter, Escherichia, Klebsiella, Pseudomonas, Serratia
	rmtC	846	AB194779	6903… 7748	Proteus, Salmonella
	rmtD	744	DQ914960	8889… 9632	Klebsiella, Pseudomonas
	rmtD2	744	HQ401565	14139… 14882	Citrobacter, Enterobacter
	rmtE	822	GU201947	55… 876	Escherichia
NUT	aadA1	972	X02340	223… 1194	Acinetobacter, Aeromonas, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Shigella, Vibrio
	aadA1b	792	M95287	3320… 4111	Pseudomonas, Serratia
	aadA2	780	X68227	166… 945	Acinetobacter, Aeromonas, Citrobacter, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Shigella, Staphylococcus, Vibrio, Yersinia
	aadA3	792	AF047479	1296… 2087	Escherichia
	aadA4	789	Z50802	1306… 2094	Acinetobacter, Aeromonas, Escherichia, Pseudomonas,
	aadA5	789	AF137361	64… 852	Acinetobacter, Aeromonas, Escherichia, Pseudomonas, Salmonella, Shigella, Staphylococcus, Vibrio
	aadA6	846	AF140629	61… 906	Pseudomonas
	aadA7	798	AF224733	32… 829	Escherichia, Salmonella, Vibrio
	aadA8	792	AF326210	1… 792	Klebsiella, Vibrio
	aadA8b	792	AM040708	1174… 1965	Escherichia
	aadA9	837	AJ420072	26773… 27609	Corynebacterium
	aadA10	834	U37105	2807… 3640	Pseudomonas
	aadA11	846	AY144590	1… 846	Pseudomonas, Riemerella
	aadA12	792	AY665771	1… 792	Escherichia, Salmonella, Yersinia
	aadA13	798	AY713504	1… 798	Escherichia, Pseudomonas, Yersinia
	aadA14	786	AJ884726	540… 1325	Pasteurella
	aadA15	792	DQ393783	1800… 2591	Pseudomonas
	aadA16	846	EU675686	3197… 4042	Escherichia, Klebsiella, Vibrio
	aadA17	792	FJ460181	774… 1565	Aeromonas
	aadA21	792	AY171244	47… 838	Salmonella
	aadA22	792	AM261837	74… 865	Escherichia, Salmonella
	aadA23	780	AJ809407	119… 898	Salmonella
	aadA24	780	AM711129	1264… 2043	Escherichia, Salmonella
	aadC	477	V01282	225… 701	Staphylococcus
	aadD aadE; see ant(6)-Ia	771	AF181950	3176… 3946	Staphylococcus
	ant(2″)-Ia	543	X04555	1296… 1829	Acinetobacter, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia, Shigella, Vibrio
	ant(4′)-Ib	771	AJ506108	209… 979	Bacillus
	ant(4′)-IIa	759	M98270	145… 903	Pseudomonas
	ant(4′)-IIb	756	AY114142	1061… 1816	Pseudomonas
	ant(6)-Ia	909	AF330699	22… 930	Enterococcus, Staphylococcus
	ant(6)-Ib	858	FN594949	27482… 28339	Campylobacter
	ant(9)-Ia	783	X02588	331… 1113	Enterococcus, Staphylococcus
	ant(9)-Ib	768	M69221	271… 1038	Enterococcus, Staphylococcus
	spc; see ant(9)-Ia
	sph	801	X64335	6557… 7354	Escherichia, Pseudomonas, Salmonella
	str	849	X92946	18060… 18908	Enterococcus, Staphylococcus, Lactococcus
NUT–ACT	ant(3″)-Ih-aac(6′)-IId	1392	AF453998	3555… 4946	Serratia
PHT	aph(2″)-Ib	900	AF337947	272… 1171	Enterococcus, Escherichia
	aph(2″)-Ic	921	U51479	196… 1116	Enterococcus
	aph(2″)-Id	906	AF016483	131… 1036	Enterococcus
	aph(2″)-Ie	906	AY743255	131… 1036	Enterococcus
	aph(3′)-Ia	816	J01839	1162… 1977	Escherichia, Klebsiella, Pseudomonas, Salmonella
	aph(3′)-Ib	816	M20305	779… 1594	Escherichia
	aph(3′)-Ic	816	X625115	410… 1225	Acinetobacter, Citrobacter, Escherichia, Klebsiella, Salmonella, Serratia, Yersinia
	aph(3′)-Id	816	Z48231	820… 1635	Escherichia
	aph(3′)-IIa	795	X57709	1… 795	Escherichia, Pseudomonas, Salmonella
	aph(3′)-IIb	807	X90856	388… 1194	Pseudomonas
	aph(3′)-IIc	813	AM743169	2377498… 2378310	Stenotrophomonas
	aph(3′)-III	795	M26832	604… 1398	Bacillus, Campylobacter, Enterococcus, Staphylococcus, Streptococcus
	aph(3′)-IV	789	X03364	277… 1065	Bacillus
	aph(3′)-Va	807	K00432	307… 1113	Streptomyces
	aph(3′)-Vb	792	M22126	373… 1164	Streptomyces
	aph(3′)-Vc	795	S81599	282… 1076	Micromonospora
	aph(3′)-Va	780	X07753	103… 882	Acinetobacter, Pseudomonas
	aph(3′)-VIb	780	AJ627643	4934… 5713	Alcaligenes
	aph(3′)-VIIa	753	M29953	131… 1036	Campylobacter
	aph(3′)-VIII	804	AF182845	1… 804	Streptomyces
	aph(3′)-XV	795	Y18050	4758… 5552	Achromobacter, Citrobacter, Pseudomonas
	aph(3″)-Ia	819	M16482	501… 1319	Streptomyces
	aph(3″)-Ib	801	AB366441	11310… 12110	Enterobacter, Escherichia, Klebsiella, Pasteurella, Pseudomonas, Salmonella, Shigella, Yersinia, Vibrio
	aph(4)-Ia	1026	V01499	231… 1256	Escherichia
	aph(4)-Ib	999	X03615	232… 1230	Streptomyces
	aph(6)-Ia	924	AY971801	1… 924	Streptomyces
	aph(6)-Ib	924	X05648	382… 1305	Streptomyces
	aph(6)-Ic	801	X01702	485… 1285	Escherichia, Pseudomonas, Salmonella
	aph(6)-Id	837	M28829	866… 1702	Enterobacter, Escherichia, Klebsiella, Pasteurella, Pseudomonas, Salmonella, Shigella, Yersinia, Vibrio
	aph(7″)-Ia	999	X03615	232… 1230	Streptomyces
	aph(9)-Ia	996	U94857	151… 1146	Legionella
	aph(9)-Ib	993	U70376	7526… 8518	Streptomyces

Last update: January 6th 2012. This table was adapted from Elbourne and Hall (2006), Magnet and Blanchard (2005), Partridge et al. (2009), Ramirez and Tolmansky (2010), Shaw et al. (1993), Vakulenko and Mobashery (2003), and data provided by B. Guerra, B. Aranda, D. Avsaroglu, B. Ruiz del Castillo, and R. Helmuth, on behalf of the Med-Vet Net (EU Network of Excellence) WP29 Project Group. The data were collected within the subproject “AME's,” with following participants representing their institutions: Agnes Perry Guyomard (ANSES), Dik Mevius (CVI), Yvonne Agerso (DTU), Katie Hopkins (HPA), Silvia Herrera (ISCIII), Alessandra Carattoli (ISS), Antonio Battisti (IZS-Rome), Stefano Lollai (IZS-Sardegna,), Lotte Jacobsen (SSI), Béla Nagy (VMRI), M. Rosario Rodicio and M. C. Mendoza (University of Oviedo, UO), Luis Martínez-Martínez (University Hospital of Valdecilla, HUV), and Bruno Gonzalez-Zorn (UCM).

ACT: Acetyltransferase; MET: Methyltransferase; NUT: Nucleotidyltransferase; PHT: Phosphotransferase.

Although the sat genes are not aminoglycoside resistance determinants, they encode streptothricin-acetyltransferases, for convenience they are included in this table.

Table 3

Acquired phenicol resistance genes.

Mechanism	Group	Gene	Gene(s) included	Length (nt)	Accession number	Coding region	Genera
Efflux	Type E-1	cmlA1	cmlA, cmlA2, cmlA4, cmlA5, cmlA6, cmlA7, cmlA8, cmlA10, cmlB	1260	M64556	601… 1860	Acinetobacter, Aeromonas, Arcanobacterium, Enterobacter, Escherichia, Klebsiella, Laribacter, Pseudomonas, Salmonella, Serratia, Staphylococcus
	Type E-2	cml	−	903	M22614	427… 1335	Escherichia
	Type E-3	floR	cmlA-like, flo, pp-flo, cmlA9	1215	AF071555	4445… 5659	Acinetobacter, Aeromonas, Bordetella, Escherichia, Pasteurella, Salmonella, Stenotrophomonas, Vibrio
	Type E-4	fexA	−	1428	AJ549214	177… 1604	Bacillus, Staphylococcus
	Type E-5	cml	−	1179	X59968	508… 1686	Streptomyces
	Type E-6	cmlv	−	1311	U09991	28… 1338	Streptomyces
	Type E-7	cmrA	cmr	1176	Z12001	993… 2168	Rhodococcus
	Type E-8	cmr	cmx	1176	U85507	3518… 4693	Corynebacterium
	−	cmlB1	−	1266	AM296481	776… 2041	Bordetella
	−	fexB	−	1410	JN192453	10637… 12046	Enterococcus
	−	pexA	−	1248	HM537013	24055… 25302	Uncultured
Inactivating enzyme	Type A-1	catA1	cat, catI, pp-cat	660	V00622	244… 903	Acinetobacter, Corynebacterium, Escherichia, Klebsiella, Salmonella, Shigella
	Type A-2	catA2	cat, catII	642	X53796	187… 828	Aeromonas, Agrobacterium, Escherichia, Haemophilus, Legionella, Klebsiella, Photobacterium, Salmonella, Vibrio
	Type A-3	catA3	cat, catIII	642	X07848	272… 913	Actinobacillus, Edwardsiella, Klebsiella, Mannheimia, Pasteurella, Shigella
	Type A-4	cat	−	654	M11587	880… 1533	Proteus
	Type A-5	cat	−	663	P20074$	1002758… 1003420	Streptomyces
	Type A-6	cat86	−	663	K00544	145… 807	Bacillus
	Type A-7	cat(pC221)	cat, catC	648	X02529	2267… 2914	Bacillus, Enterococcus, Lactobacillus, Staphylococcus, Streptococcus
	Type A-8	cat(pC223)	cat	648	AY355285	1000… 1647	Enterococcus, Lactococcus, Listeria, Staphylococcus
	Type A-9	cat(pC194)	cat, cat-TC	651	NC_002013	1260… 1910	Bacillus, Enterococcus, Lactobacillus, Staphylococcus, Streptococcus
	Type A-10	cat	−	687	AY238971	1055… 1741	Bacillus
	Type A-11	catP	catD	624	U15027	2953… 3576	Clostridium, Neisseria
	Type A-12	catS	−	492§	X74948	1… 492	Streptococcus
	Type A-13	cat	−	624	M35190	309… 932	Campylobacter
	Type A-14	cat	−	651	S48276	479… 1129	Listonella, Photobacterium, Proteus, Vibrio
	Type A-15	catB	−	660	M93113	145… 804	Clostridium
	Type A-16	catQ	−	660	M55620	459… 1118	Clostridium
	Type B-1	catB1	cat	630	M58472	148… 777	Agrobacterium
	Type B-2	catB2	−	633	AF047479	5957… 6589	Acinetobacter, Aeromonas, Bordetella, Escherichia, Klebsiella, Pasteurella, Pseudomonas, Salmonella
	Type B-3	catB3	catB4, catB5, catB6, catB8	633	AJ009818	883… 1515	Acinetobacter, Aeromonas, Bordetella, Comamonas, Enterobacter, Escherichia, Klebsiella, Kluyvera, Morganella, Proteus, Pseudomonas, Salmonella, Serratia, Stenotrophomonas
	Type B-4	catB7	−	639	AF036933	177… 815	Pseudomonas
	Type B-5	catB9	−	630	AF462019	27… 656	Vibrio
	Type B-6	catB10	−	633	AJ878850	1197… 1829	Pseudomonas
rRNA methylase	−	cfr$	−	1050	AJ579365	6290… 7339	Bacillus, Enterococcus, Escherichia, Jeotgalicoccus, Macrococcus, Proteus, Staphylococcus

Last update: December 16th 2011. Adapted from Partridge et al. (2009), Roberts and Schwarz (2009), Schwarz et al. (2004), and nucleotide BLAST searches.

Partial sequence.

The multidrug resistance gene cfr confers resistance against phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A (see Table 4; Kehrenberg et al., 2007).

Table 4

Acquired macrolide-lincosamide-streptogramin B (MLS) resistance genes.

Mechanism	Gene	Gene(s) included	Length (nt)	Accession number	Coding region	Genera
Efflux	car(A)	−	1656	M80346	411… 2066	Streptomyces
	lmr(A)	−	1446	X59926	318… 1763	Streptomyces
	lsa(A)	abc-23	1497	AY225127	41… 1537	Enterococcus
	lsa(B)	orf3	1479	AJ579365	4150… 5628	Staphylococcus
	lsa(C)	−	1479	HM990671	5193… 6671	Gardnerella, Streptococcus
	lsa(E)	−	1485	JQ861959	6673… 8157	Enterococcus, Staphylococcus
	mef(A)	mef(E)	1218	U70055	314… 1531	Acinetobacter, Bacteroides, Citrobacter, Clostridium, Corynebacterium, Enterococcus, Enterobacter, Escherichia, Fusobacterium, Gemella, Haemophilus, Klebsiella, Lactobacillus, Micrococcus, Morganella, Neisseria, Pantoea, Providencia, Proteus, Ralstonia, Rothia, Pseudomonas, Salmonella, Serratia, Staphylococcus, Streptococcus, Stenotrophomonas, Ureaplasma
	mef(B)	−	1230	FJ196385	11084… 12313	Escherichia
	msr(A)	msr(B), msr(SA)	1467	X52085	343… 1809	Corynebacterium, Enterobacter, Enterococcus, Gemella, Pseudomonas, Staphylococcus, Streptococcus, Ureaplasma
	msr(C)	−	1479	AY004350	496… 1974	Enterococcus
	msr(D)	mel, orf5	1464	AF274302	2462… 3925	Acinetobacter, Bacteroides, Citrobacter, Clostridium, Corynebacterium, Enterococcus, Enterobacter, Escherichia, Gemella, Fusobacterium, Klebsiella, Morganella, Neisseria, Proteus, Providencia, Pseudomonas, Ralstonia, Staphylococcus, Streptococcus, Serratia, Stenotrophomonas, Ureaplasma
	msr(E)	mel	1476	AY522431	20650… 22125	Acinetobacter, Citrobacter, Escherichia, Klebsiella, Mannheimia, Pasteurella, Serratia
	ole(B)	−	1710	L36601	1421… 3130	Streptomyces
	ole(C)	−	978	L06249	1528… 2505	Streptomyces
	srm(B)	−	1653	X63451	558… 2210	Streptomyces
	tlc(C)	−	1647	M57437	277… 1923	Streptomyces
	vga(A)	vga	1569	M90056	909… 2477	Staphylococcus
	vga(A)LC	vga	1569	DQ823382	1… 1569	Staphylococcus
	vga(B)	−	1659	U82085	629… 2287	Enterococcus, Staphylococcus
	vga(C)	−	1569	NC_013034	12570… 14138	Staphylococcus
	vga(D)	−	1578	GQ205627	1394… 2971	Enterococcus
	vga(E)	−	1575	FR772051	8741… 10315	Staphylococcus
Inactivating enzymea	ere(A)	−	1221	AY183453	2730… 3950	Achromobacter, Aermonas, Citrobacter, Enterobacter, Escherichia, Klebsiella, Laribacter, Pantoeae, Providencia, Pseudomonas, Serratia, Salmonella, Staphylococcus, Stenotrophomonas
	ere(B)	−	1260	X03988	383… 1642	Acinetobacter, Citrobacter, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Staphylococcus
Inactivating enzymeb	vgb(A)	vgb	900	M20129	641… 1540	Enterococcus, Staphylococcus
	vgb(B)	−	888	AF015628	399… 1286	Staphylococcus
Inactivating enzymec	lnu(A)	lin(A), lin(A')	486	M14039	413… 898	Clostridium, Lactobacillus, Staphylococcus
	lnu(B)	lin(B)	804	AJ238249	127… 930	Clostridium, Enterococcus, Staphylococcus, Streptococcus
	lnu(C)	−	495	AY928180	1150… 1644	Haemophilus, Streptococcus
	lnu(D)	−	495	EF452177	19… 513	Streptococcus
	lnu(F)	lin(F), lin(G), linF	822	EU118119	1030… 1851	Escherichia, Salmonella
	vat(A)	−	660	L07778	258… 917	Staphylococcus
	vat(B)	−	639	U19459	67… 705	Enterococcus, Staphylococcus
	vat(C)	−	639	AF015628	1307… 1945	Staphylococcus
	vat(D)	sat(A)	630	L12033	162… 791	Enterococcus
	vat(E)	sat(G), vat (E-3)–vat(E-8)	645	AF139725	63… 707	Enterococcus, Lactobacillus
	vat(F)	−	666	AF170730	70… 735	Yersinia
	vat(H)	vat(G)	651	GQ205627	3037… 3687	Enterococcus
Inactivating enzymed	mph(A)	mph(K)	906	D16251	1626… 2531	Aeromonas, Escherichia, Citrobacter, Enterobacter, Klebsiella, Pantoeae, Pseudomonas, Proteus, Serratia, Shigella, Stenotrophomonas
	mph(B)	mph(B)	909	D85892	1159… 2067	Escherichia, Enterobacter, Proteus, Pseudomonas
	mph(C)	mph(BM)	900	AF167161	5665… 6564	Staphylococcus, Stenotrophomonas
	mph(D)	−	840§	AB048591	1… 840	Escherichia, Klebsiella, Pantoea, Proteus, Pseudomonas, Stenotrophomonas
	mph(E)	mph, mph1, mph2	885	DQ839391	12873… 13757	Acinetobacter, Citrobacter, Escherichia, Klebsiella, Mannheimia, Pasteurella, Serratia
	mph(F)	mph(B), mph(E)	900	AM206957	4187… 5086	Unknown
rRNA methylase	cfr$	−	1050	AM408573	10028… 11077	Bacillus, Enterococcus, Escherichia, Jeotgalicoccus, Macrococcus, Proteus, Staphylococcus
	erm(A)	erm(TR)	732	X03216	4551… 5282	Aggregatibacter, Bacteriodes, Enterococcus, Helcococcus, Peptostreptococcus, Prevotella, Staphylococcus, Streptococcus
	erm(B)	erm(2), erm(AM), erm(AMR), erm(BC), erm(BP), erm(Z), erm(BZ1, BZ2), erm(IP), erm(P), erm, erm(80)	738	M36722	714… 1451	Aggregatibacter, Acinetobacter, Aerococcus, Arcanobacterium, Bacillus, Bacteriodes, Citrobacter, Corynebacterium, Clostridium, Enterobacter, Escherichia, Eubacterium, Enterococcus, Fusobacterium, Gemella, Haemophilus, Klebsiella, Lactobacillus, Micrococcus, Neisseria, Pantoeae, Pediococcus, Peptostreptococcus, Porphyromonas, Proteus, Pseudomonas, Ruminococcus, Rothia, Serratia, Staphylococcus, Streptococcus, Ureaplasma, Treponema, Wolinella
	erm(C)	erm(IM), erm(M)	735	M19652	988… 1722	Aggregatibacter, Actinomyces, Arcanobacterium, Bacillus, Bacteriodes, Clostridium, Corynebacterium, Escherichia, Eubacterium, Enterococcus, Haemophilus, Lactobacillus, Macrococcus, Micrococcus, Neisseria, Prevotella, Peptostreptococcus, Staphylococcus, Streptococcus, Wolinella
	erm(D)	erm(J), erm(K)	864	M29832	430… 1293	Bacillus, Salmonella
	erm(E)	erm(E2)	1146	X51891	190… 1335	Bacteroides, Eubacterium, Fusobacterium, Ruminococcus, Saccharopolyspora, Shigella, Streptomyces
	erm(F)	erm(FS), erm(FU)	801	M14730	241… 1041	Aggregatibacter, Actinomyces, Bacteroides, Capnocytophaga, Clostridium, Corynebacterium, Eubacterium, Enterococcus, Fusobacterium, Gardnerella, Haemophilus, Lactobacillus, Mobiluncus, Neisseria, Porphyromonas, Prevotella, Peptostreptococcus, Ruminococcus, Shigella, Selenomonas, Staphylococcus, Streptococcus, Treponema, Veillonella, Wolinella
	erm(G)	−	735	M15332	672… 1406	Bacillus, Bacteroides, Catenibacterium, Lactobacillus, Prevotella, Porphyromonas, Staphylococcus
	erm(H)	car(B)	900	M16503	244… 1143	Streptomyces
	erm(I)	mdm(A)	−	−	−	Streptomyces
	erm(N)	tlr(D)	876	X97721	160… 1035	Streptomyces
	erm(O)	lrm, srm(A)	783	M74717	40… 822	Streptomyces
	erm(Q)	−	774	L22689	262… 1035	Aggregatibacter, Bacteroides, Clostridium, Staphylococcus, Streptococcus, Wolinella
	erm(R)	−	1023	M11276	333… 1355	Aeromicrobium, Arthrobacter
	erm(S)	erm(SF), tlr(D)	960	M19269	460… 1419	Streptomyces
	erm(T)	erm(GT), erm(LF)	735	M64090	168… 902	Enterococcus, Lactobacillus, Staphylococcus, Streptococcus
	erm(U)	lrm(B)	837	X62867	361… 1197	Streptomyces
	erm(V)	erm(SV)	780	U59450	397… 1176	Eubacterium, Fusobacterium, Streptomyces
	erm(W)	myr(B)	936	D14532	1039… 1974	Micromonospora
	erm(X)	erm(CD), erm(Y)	855	M36726	296… 1150	Arcanobacterium, Bifidobacterium, Corynebacterium, Propionibacterium
	erm(Y)	erm(GM)	735	AB014481	556… 1290	Staphylococcus
	erm(Z)	srm(D)	849	AM709783	2817… 3665	Streptomyces
	erm(30)	pikR1	1011	AF079138	1283… 2293	Streptomyces
	erm(31)	pikR2	969	AF079138	154… 1122	Streptomyces
	erm(32)	tlr(B)	843	AJ009971	1790… 2632	Streptomyces
	erm(33)	−	732	AJ313523	163… 894	Staphylococcus
	erm(34)	−	846	AY234334	355… 1200	Bacillus
	erm(35)	−	801	AF319779	33… 833	Bacteriodes
	erm(36)	−	846	AF462611	186… 1031	Micrococcus
	erm(37)	erm(MT)	540	AE000516	2229013… 2229552	Mycobacterium
	erm(38)	−	1161	AY154657	63… 1223	Mycobacterium
	erm(39)	−	741	AY487229	2153… 2893	Mycobacterium
	erm(40)	−	756	AY570506	2035… 2790	Mycobacterium
	erm(41)	−	522	EU590124	258… 779	Mycobacterium
	erm(42)	erm(MI)	906	FR734406	1… 906	Mannheimia, Pasteurella, Photobacterium

Last update: January 6th 2012. Adapted from http://faculty.washington.edu/marilynr/

Partial sequence.

The multidrug resistance gene cfr confers resistance against phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A (see Table 3; Kehrenberg et al., 2007).

Esterase,

Lyase,

Transferase, and

Phosphorylase.

Table 5

Acquired quinolone resistance genes.

Gene	Length (nt)	Accession number	Coding region	Genera
qepA	1536	AB263754	7052… 8587	Escherichia
qepA2	1536	EU847537	1672… 3207	Escherichia
qnrA1a	657	AY070235	303… 959	Citrobacter, Escherichia, Klebsiella, Proteus
qnrA2a	657	AY675584	1… 657	Klebsiella, Shewanella
qnrA3a	657	DQ058661	1… 657	Shewanella
qnrA4a	657	DQ058662	1… 657	Shewanella
qnrA5a	657	DQ058663	1… 657	Shewanella
qnrA6a	657	DQ151889	1… 657	Proteus
qnrA7a	657	GQ463707	1… 657	Shewanella
qnrB1a	645	DQ351241	37… 681	Klebsiella
qnrB2a	645	DQ351242	1… 645	Citrobacter, Enterobacter, Klebsiella, Salmonella
qnrB3a	645	DQ303920	37… 681	Escherichia
qnrB4a	645	DQ303921	4… 648	Citrobacter, Enterobacter, Escherichia, Klebsiella
qnrB5a	645	DQ303919	37… 681	Salmonella
qnrB6a	645	EF520349	37… 681	Enterobacter, Panthoea
qnrB7a	645	EU043311	1… 645	Enterobacter, Klebsiella
qnrB8a	645	EU043312	1… 645	Citrobacter
qnrB9a	645	EF526508	1… 645	Citrobacter
qnrB10a	645	DQ631414	37… 681	Citrobacter, Enterobacter, Klebsiella
qnrB11a	645	EF653270	4… 648	Citrobacter
qnrB12a	645	AM774474	2435… 3079	Citrobacter
qnrB13a	645	EU273756	37… 681	Citrobacter
qnrB14a	645	EU273757	37… 681	Citrobacter
qnrB15a	645	EU302865	37… 681	Citrobacter
qnrB16a	645	EU136183	37… 681	Citrobacter
qnrB17a	645	AM919398	37… 681	Citrobacter
qnrB18a	645	AM919399	37… 681	Citrobacter
qnrB19a	645	EU432277	1… 645	Escherichia, Klebsiella, Salmonella
qnrB20a	645	AB379831	37… 681	Escherichia
qnrB21a	645	FJ611948	1… 645	Escherichia
qnrB22a	645	FJ981621	37… 681	Citrobacter
qnrB23a	645	FJ981622	37… 681	Citrobacter
qnrB24a	645	HM192542	37… 681	Citrobacter
qnrB25a	645	HQ172108	1… 645	Citrobacter
qnrB26a	645	HM439644	1… 645	Citrobacter
qnrB27a	645	HM439641	1… 645	Citrobacter
qnrB28a	645	HM439643	1… 645	Citrobacter
qnrB29a	645	HM439649	37… 681	Citrobacter
qnrB30a	645	HM439650	37… 681	Citrobacter
qnrB31a	645	HQ418999	1… 645	Klebsiella
qnrB32a	645	JN173054	37… 681	Citrobacter
qnrB33a	645	JN173055	36… 680	Citrobacter
qnrB34a	645	JN173056	39… 683	Citrobacter
qnrB35a	645	JN173057	2307… 2951	Citrobacter
qnrB36a	645	JN173058	37… 681	Citrobacter
qnrB37a	645	JN173059	36… 680	Citrobacter
qnrB38a	645	JN173060	2307… 2951	Citrobacter
qnrB39a	−	NZ_ABWL02000005	−	−
qnrB40a	645	JN166689	16… 660	Citrobacter
qnrB41a	645	JN166690	37… 681	Citrobacter
qnrB42a	645	JN680743	1… 645	Klebsiella
qnrB43a	644	JQ349152	37… 680	Escherichia
qnrB44a	644	JQ349153	37… 680	Escherichia
qnrB45a	644	JQ349152	37… 680	Escherichia
qnrB46a	644	JQ349154	37… 680	Escherichia
qnrB47a	644	JQ349155	37… 680	Escherichia
qnrB48a	645	JQ762640	37… 681	Citrobacter
qnrB49a	645	JQ582718	37… 681	Citrobacter
qnrB50–qnrB51 not public yet
qnrB52a	645	EF488762	1… 645	Proteus
qnrB53a	645	HQ704413	37… 681	Klebsiella
qnrB54–qnrB59 not public yet
qnrCa	666	EU917444	1717… 2382	Proteus
qnrDa	645	EU692908	1… 645	Escherichia, Morganella, Proteus, Providencia, Salmonella
qnrS1a	657	AB187515	9737… 10393	Enterobacter, Escherichia, Klebsiella, Proteus, Salmonella, Shigella
qnrS2a	657	DQ485530	1… 657	Aeromonas, Salmonella
qnrS3a	>656	EU077611	<1… 656	Escherichia
qnrS4a	657	FJ418153	1… 657	Salmonella
qnrS5a	657	HQ631377	1… 657	Aeromonas
qnrS6a	657	HQ631376	1… 657	Aeromonas
qnrS7–qnrS8 not public yet

Last update: July 8th 2012. According to http://www.lahey.org/qnrStudies

and nucleotide BLAST searches.

Table 6

Acquired tetracycline resistance genes.

Mechanism	Gene	Length (nt)	Accession number	Coding region	Genera
Efflux	otr(B)	1692	AF079900	40… 1731	Mycobacterium, Streptomyces
	otr(C)	1056	AY509111	324… 1379	Streptomyces
	tcr	1539	D38215	516… 2054	Streptomyces
	tet(A)	1200	X00006	1328… 2527	Acinetobacter, Aeromonas, Alcaligenes, Bordetella, Chryseobacterium, Citrobacter, Edwardsiella, Enterobacter, Escherichia, Flavobacterium, Klebsiella, Laribacter, Plesiomonas, Proteus, Pseudomonas, Salmonella, Serratia, Shigella, Variovorax, Veillonella, Vibrio
	tetA(P)	1263	L20800	1063… 2325	Clostridium
	tet(B)	1206	J01830	1608… 2813	Acinetobacter, Actinobacillus, Aeromonas, Aggregatibacter, Brevundimonas, Citrobacter, Enterobacter, Erwinia, Escherichia, Haemophilus, Klebsiella, Mannheimia, Moraxella, Neisseria, Pantoea, Pasteurella, Photobacterium, Plesiomonas, Proteus, Providencia, Pseudomonas, Roseobacter, Salmonella, Serratia, Shigella, Treponema, Vibrio, Yersinia
	tet(C)	1191	X01654	86… 1276	Aeromonas, Bordetella, Chlamydia, Citrobacter, Enterobacter, Escherichia, Francisella, Halomonas, Klebsiella, Proteus, Pseudomonas, Roseobacter, Salmonella, Serratia, Shigella, Vibrio
	tet(D)	1185	X65876	1521… 2705	Aeromonas, Alteromoas, Citrobacter, Edwardsiella, Enterobacter, Escherichia, Halomonas, Klebsiella, Morganella, Pasteurella, Photobacterium, Proteus, Salmonella, Shewanella, Shigella, Vibrio, Yersinia
	tet(E)	1218	L06940	21… 1238	Aeromonas, Alcaligenes, Escherichia, Flavobacterium, Plesiomonas, Proteus, Providencia, Pseudomonas, Roseobacter, Serratia, Vibrio
	tet(G)	1128	AF071555	6644… 7771	Acinetobacter, Brevundimonsa, Escherichia, Fusobacterium, Mannheimia, Ochrobactrum, Pasteurella, Proteus, Providencia, Pseudomonas, Roseobacter, Salmonella, Shewanella, Vibrio
	tet(H)	1203	U00792	716… 1918	Acinetobacter, Actinobacillus, Histophilus, Mannheimia, Moraxella, Pasteurella, Psychrobacter
	tet(J)	1197	AF038993	1084… 2280	Escherichia, Morganella, Proteus
	tet(K)	1380	M16217	305… 1684	Bacillus, Clostridium, Enterococcus, Eubacterium, Haemophilus, Lactobacillus, Listeria, Mycobacterium, Nocardia, Peptostreptococcus, Staphylococcus, Streptococcus, Streptomyces
	tet(L)	1377	D00006	189… 1565	Acinetobacter, Actinobacillus, Actinomyces, Bacillus, Bifidobacterium, Citrobacter, Clostridium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Fusobacterium, Geobacillus, Kurthia, Lactobacillus, Listeria, Mannheimia, Morganella, Mycobacterium, Nocardia, Ochrobactrum, Oceanobacillus, Paenibacillus, Pasteurella, Pediococcus, Peptostreptococcus, Proteus, Pseudomonas, Rahnella, Salmonella, Sporosarcina, Staphylococcus, Streptococcus, Streptomyces, Variovorax, Veillonella, Virgibacillus
	tet(V)	1260	AF030344	462… 1721	Mycobacterium
	tet(Y)	1176	AF070999	1680… 2855	Aeromonas, Escherichia, Photobacterium
	tet(Z)	1155	AF121000	11880… 13034	Corynebacterium, Lactobacillus
	tet(30)	1185	AF090987	1130… 2314	Agrobacterium
	tet(31)	1233	AJ250203	1651… 2883	Aeromonas, Gallibacterium
	tet(33)	1224	AJ420072	22940… 24163	Arthrobacter, Corynebacterium
	tet(35)	1110	AF353562	2213… 3322	Stenotrophomonas, Vibrio
	tet(38)	1353	AY825285	1… 1353	Staphylococcus
	tet(39)	1188	AY743590	749… 1936	Acinetobacter, Alcaligenes, Brevundimonas, Enterobacter, Providencia, Stenotrophomonas
	tet(40)	1221	AM419751	14211… 15431	Clostridium
	tet(41)	1182	AY264780	1825… 3006	Serratia
	tet(42)	1287	EU523697	687… 1973	Bacillus, Microbacterium, Micrococcus, Paenibacillus, Pseudomonas, Staphylococcus
	tet(43)	1560	GQ244501	60… 1619	Uncultured
Enzymatic	tet(X)	1167	M37699	586… 1752	Bacteroides, Pseudomonas, Sphingobacterium
	tet(34)	465	AB061440	306… 770	Aeromonas, Pseudomonas, Serratia
	tet(37)	327	AF540889	1… 327	Uncultured
Ribosomal protection	otr(A)	1992	X53401	349… 2340	Bacillus, Mycobacterium, Streptomyces
	tetB(P)	1959	L20800	2309… 4267	Clostridium
	tet(M)	1920	U08812	1981… 3900	Abiotrophia, Acinetobacter, Actinomyces, Aerococcus, Aeromonas, Afipia, Arthrobacter, Bacillus, Bacterionema, Bacteroides, Bifidobacterium, Brachybacterium, Catenibacterium, Clostridium, Corynebacterium, Edwardsiella, Eikenella, Enterobacter, Enterococcus, Erysipelothrix, Escherichia, Eubacterium, Flavobacterium, Fusobacterium, Gardnerella, Gemella, Granulicatella, Haemophilus, Kingella, Klebsiella, Kurthia, Lactobacillus, Lactococcus, Listeria, Microbacterium, Mycoplasma, Neisseria, Paenibacillus, Pantoea, Pasteurella, Peptostreptococcus, Photobacterium, Prevotella, Pseudoalteromonas, Pseudomonas, Ralstonia, Selenomonas, Serratia, Shewanella, Staphylococcus, Streptococcus, Streptomyces, Ureaplasma, Veillonella, Vibrio
	tet(O)	1920	M18896	207… 2126	Actinobacillus, Aerococcus, Anaerovibrio, Bifidobacterium, Butyrivibrio, Campylobacter, Clostridium, Enterococcus, Eubacterium, Fusobacterium, Gemella, Lactobacillus, Megasphaera, Mobiluncus, Neisseria, Peptostreptococcus, Psychrobacter, Staphylococcus, Streptococcus
	tet(Q)	1926	Z21523	362… 2287	Anaerovibrio, Bacteroides, Capnocytophaga, Clostridium, Eubacterium, Fusobacterium, Gardnerella, Lactobacillus, Mitsuokella, Mobiluncus, Neisseria, Peptostreptococcus, Porphyromonas, Prevotella, Ruminococcus, Selenomonas, Streptococcus, Subdolgranulum, Veillonella
	tet(S)	1926	L09756	447… 2372	Enterococcus, Lactobacillus, Lactococcus, Listeria, Staphylococcus, Streptococcus, Veillonella
	tet(T)	1956	L42544	478… 2433	Lactobacillus, Streptococcus
	tet(W)	1920	AJ222769	3687… 5606	Acidaminococcus, Actinomyces, Arcanobacterium, Bacillus, Bacteroides, Bifidobacterium, Butyrivibrio, Clostridium, Fusobacterium, Lactobacillus, Megasphaera, Mitsuokella, Neisseria, Porphyromonas, Prevotella, Roseburia, Selenomonas, Staphylococcus, Streptococcus, Streptomyces, Subdolgranulum, Veillonella
	tet(32)	1920	DQ647324	181… 2100	Eubacterium, Streptococcus
	tet(36)	1923	AJ514254	2534… 4456	Bacteroides, Clostridium, Lactobacillus
	tet(44)	1923	FN594949	25245… 27167	Campylobacter, Clostricium
	tet	1920	M74049	343… 2261	Streptomyces
Unknown	tet(U)	318	U01917	413… 730	Enterococcus, Staphylococcus, Streptococcus

Last update: January 6th 2012. Adapted from http://faculty.washington.edu/marilynr/. The efflux genes tet(45) and tet(46) have been named but not yet published.

Table 7

Acquired trimethoprim resistance genes.

Gene	Sub-family	Gene(s) included	Length (nt)	Accession number	Coding region	Genera
dfrA1	dfrA1-group	dhfrIb, dfr1, dhfrI	474	X00926	236… 709	Actinobacter, Enterobacter, Escherichia, Klebsiella, Laribacter, Morganella, Pasteurella, Proteus, Pseudomonas, Salmonella, Serratia, Shigella, Vibrio
dfrA3	−	−	489	J03306	103… 591	Salmonella
dfrA5	dfrA1-group	dhfrV, dfrV	474	X12868	1306… 1779	Actinobacter, Aeromonas, Comomonas, Enterobacter, Escherichia, Klebsiella, Pseudomonas, Salmonella, Vibrio
dfrA6	dfrA1-group	dfrVI	474	Z86002	336… 809	Proteus
dfrA7	dfrA1-group	dhfrVII, dfrVII, dfrA17	474	X58425	594… 1067	Actinobacter, Escherichia, Proteus, Salmonella, Shigella
dfrA8	−	−	510	U10186	711… 1220	Escherichia
dfrA9	−	−	534	X57730	726… 1259	Escherichia
dfrA10	−	−	564	L06418	5494… 6057	Actinobacter, Escherichia, Klebsiella, Salmonella
dfrA12	dfrA12-group	dhfrXII, dfr12	498	Z21672	310… 807	Actinobacter, Aeromonas, Citrobacter, Edwardsiella, Enterobacter, Escherichia, Klebsiella, Proteus, Providencia, Pseudomonas, Serratia, Salmonella, Staphylococcus, Stenotrophomonas
dfrA13	dfrA12-group	−	498	Z50802	718… 1215	Escherichia
dfrA14	dfrA1-group	dhfrIb	474	Z50805	72… 545	Achromobacter, Aeromonas, Escherichia, Klebsiella, Salmonella, Vibrio
dfrA15	dfrA1-group	dhfrXVb	474	Z83311	357… 830	Actinobacter, Enterobacter, Escherichia, Klebsiella, Morganella, Proteus, Pseudomonas, Vibrio
dfrA16	dfrA1-group	dhfrXVI, dfr16	474	AF174129	1352… 1825	Aeromonas, Escherichia, Klebsiella, Salmonella
dfrA17	dfrA1-group	dhfrXVII, dfr17	474	AB126604	98… 571	Actinobacter, Enterobacter, Escherichia, Klebsiella, Kluyvera, Laribacter, Pseudomonas, Salmonella, Serratia, Shigella, Staphylococcus, Stenotrophomonas
dfrA18	−	dfrA19	570	AJ310778	7004… 7573	Enterobacter, Klebsiella, Salmonella
dfrA20	−	−	510	AJ605332	1304… 1813	Pasteurella
dfrA21	dfrA12-group	dfrxiii	498	AY552589	1… 498	Escherichia, Klebsiella, Salmonella
dfrA22	dfrA12-group	dfr22, dfr23	498	AJ628423	325… 822	Escherichia, Klebsiella, Serratia
dfrA23	−	−	561	AJ746361	6743… 7303	Salmonella
dfrA24	−	−	558	AJ972619	83… 640	Escherichia
dfrA25	dfrA1-group	−	459	DQ267940	54… 512	Citrobacter, Klebsiella, Salmonella, Serratia
dfrA26	−	–	552	AM403715	303… 854	Escherichia
dfrA27	dfrA1-group	dfr	474	EU675686	2543… 3016	Aeromonas, Escherichia, Klebsiella, Serratia, Vibrio
dfrA28	dfrA1-group	−	474	FM877476	116… 589	Aeromonas
dfrA29	−	dfrVII, dfrA7	472	AM237806	615… 1086	Salmonella
dfrA30	−	dhfrV	474	AM997279	705… 1178	Klebsiella
dfrA31	−	dfr6	474	AB200915	1832… 2305	Escherichia, Vibrio
dfrA32	dfrA1-group	−	474	GU067642	535… 1008	Laribacter, Salmonella
dfrA33	dfrA12-group	−	498	FM957884	88… 585	Unknown
dfrB1	−	dhfrIIa, dfr2a	237	U36276	717… 953	Aeromonas, Bordetella, Escherichia, Klebsiella, Pseudomonas
dfrB2	−	dhfrIIb, dfr2b	237	J01773	809… 1045	Escherichia
dfrB3	−	dhfrIIc, dfr2c	237	X72585	5957… 6193	Aeromonas, Enterobacter, Escherichia, Klebsiella
dfrB4	−	dfr2d	237	AJ429132	69… 305	Aeromonas, Escherichia, Klebsiella
dfrB5	−	dfr2e	237	AY943084	2856… 3092	Pseudomonas
dfrB6	−	−	237	DQ274503	394… 630	Salmonella
dfrB7	−	−	237	DQ993182	244… 480	Aeromonas
dfrB8	−	−	249	GU295656	1048… 1296	Aeromonas
dfrD	−	−	489	Z50141	94… 582	Listeria, Staphylococcus
dfrG	−	−	498	AB205645	1013… 1510	Enterococcus, Staphylococcus
dfrK		−	492	FM207105	2788… 3279	Enterococcus, Staphylococcus

Last update: December 12th 2011. Partly adapted from Grape (2006), Partridge et al. (2009), and nucleotide BLAST searches.

Table 2

β-lactamases and ESBLs families.

Amber class A β-lactamases and ESBLs	Number of variants*	Amber class B β-lactamases and MBLs	Number of variants*	Amber class C β-lactamases and ESBLs	Number of variants*	Amber class D β-lactamases and ESBLs	Number of variants*
blaACI	1	blaB	13	blaACCa	5	ampH	1
blaAER	1	blaCGB	2	blaACTa	14	ampS	1
blaAST	1	blaDIM	1	blaADC	54	blaLCR	1
blaBEL	3	blaEBR	1	blaBIL	1	blaNPS	1
blaBES	1	blaGIM	1	blaBUT	2	blaOXAa	247
blaBIC	1	blaGOB	18	blaCFEa	1	loxA	1
blaBPS	5	blaIMPa	37	blaCMG	1
blaCARB	14	blaINDa	7	blaCMYa	92
blaCIA	1	blaJOHN	1	blaDHAa	8
blaCGA	1	blaMUS	1	blaFOXa	10
blaCKO	5	blaNDM	6	blaLATa	1
blaCME	2	blaSIM	1	blaLENc	26
blaCTX-Ma	130	blaSPM	1	blaMIRa	5
blaDES	1	blaTUS	1	blaMOR	1
blaERP	1	blaVIMa	34	blaMOXa	8
blaFAR	1	cepA	7	blaOCH	7
blaFONA	6	cfiA	16	blaOKP-Ac	16
blaGESa,b	22	cphA	8	blaOKP-Bc	20
blaHERA	8	imiH	1	blaOXYc	23
blaIMI	3	imiS	1	blaTRU	1
blaKLUAd	12			blaZEG	1
blaKLUCd	2			cepH	1
blaKLUG	1
blaKLUY	4
blaKPCa	12
blaLUT	6
blaMAL	2
blaMOR	1
blaNMC-A	1
blaPERa	7
blaPME	1
blaPSE	4
blaRAHN	2
blaROB	1
blaSED	1
blaSFC	1
blaSFO	1
blaSHVa	166
blaSMEa	3
blaTEMa	201
blaTLA	1
blaTOHO	1
blaVEBa	7
blaZ	1
cdiA	1
cfxA	6
cumA	1
hugA	1
penA	1

Last update: June 8th 2012.

According to http://www.lahey.org/Studies.

GES and IBC-type ESBLs have all been renamed as blaGES according to Weldhagen et al. (2006).

According to http://www.pasteur.fr/ip/easysite/go/03b-00002u-03q/beta-lactamase-enzyme-variants.

blaKLUA, blaKLUC, blaKLUG, and blaKLUY seem to be the chromosomal progenitors of acquired CTX-M group 2, 1, 8, and 9 genes, respectively (Saladin et al., 2002; Olson et al., 2005).

To the subsection dealing with the “Resistance mechanisms” of the AMINOGLYCOSIDES we would like to add that to date six additional methylases have been reported, i.e., npmA, rmtA, rmtB, rmtC, rmtD, and rmtE (Courvalin, 2008; Doi et al., 2008; Davis et al., 2010). Futhermore, that within the three major classes (AAC, ANT, and APH) an additional subdivision can be made based on the enzymes' target sites within the aminoglycoside molecules: i.e., there are four acetyltransferases: AAC(1), AAC(2′), AAC(3), and AAC(6′); five nucleotidyltransferases: ANT(2″), ANT(3″), ANT(4′), ANT(6), and ANT(9); and seven phosphotransferases: APH(2″), APH(3′), APH(3″), APH(4), APH(6), APH(7″), and APH(9).

To the subsection β-LACTAM, Resistance, mechanisms we would like to add that in recent years acquired genes encoding ESBLs have become a major concern (Bradford, 2001). Over time, the genes for the parent enzymes blaTEM−1, blaTEM−2, and blaSHV−1 have undergone point mutations which resulted in amino acid substitutions that changed the substrate spectrum to that of ESBLs, starting with blaTEM−3 and blaSHV−2 (Bradford, 2001).

Because chloramphenicol is not an actual antibiotic class the subsection of CHLORAMPHENICOL should be called PHENICOLS. Concerning the history of PHENICOLS, it is worthwhile to know the first antibiotic, chloramphenicol, originally referred to as chloromycetin, was isolated already in 1947 from Streptomyces venezuelae (Ehrlich et al., 1947).

Besides the inactivating enzymes (chloramphenicol acetyltransferases), there are also reports on other phenicol resistance systems, such as the inactivation by phosphotransferases, mutations of the target site, permeability barriers, and efflux systems (Schwarz et al., 2004). Of the latter mechanism, cmlA and floR are the most commonly known genes in Gram-negative bacteria (Bissonnette et al., 1991; Briggs and Fratamico, 1999).

The macrolides (subsection MACROLIDES–LINCOSAMIDES–STREPTOGRAMIN B) have a similar mode of antibacterial action, comparable antibacterial spectra and in part overlapping binding sites at the ribosome as two other antibiotic classes, i.e., lincosamides and streptogramin antibiotics (comprising streptogramin A and B compounds that act synergistically). Consequently, these antibiotics, although chemically distinct, have been clustered together as MLS antibiotics (Roberts, 1996). Macrolides, lincosamides and streptogramins all inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria (Weisblum, 1995; Roberts, 2002).

To Resistance mechanisms of the subsection MACROLIDES–LINCOSAMIDES–STREPTOGRAMIN B. Shortly after the introduction of erythromycin into clinical setting in the 1950s, bacterial resistance to this antibiotic was reported for the first time in staphylococci (Weisblum, 1995). Since then a large number of bacteria have been identified that are resistant to MLS due to the presence of various different genes. The resistance determinants responsible include rRNA methylases that modify the ribosomal target sites, ABC transporters, and efflux proteins of the Major Facilitator Superfamily, as well as genes for inactivating enzymes (Roberts et al., 1999; Roberts, 2008). The latter group can be further subdivided into esterases, lyases, phosphorylases, and transferases (Table 4).

The most common mechanism of MLSB resistance is due to the presence of rRNA methylases, encoded by the erm genes. These enzymes methylate the adenine residue(s) resulting in MLSB resistance. The methylated adenine(s) prevents the drugs from binding to the 50S ribosomal subunit. The other two mechanisms efflux and enzymatic inactivation result in resistance to only 1 or 2 classes of antibiotics belonging to the MLS group.

There are currently 77 MLS resistance genes recognized. A new MLS gene must have <79% amino acid identity with all previously characterized MLS genes before receiving a unique name (Roberts et al., 1999; Roberts, 2008). For an actual list of the MLS acquired resistance genes we refer to the website of Dr. Marilyn Roberts, http://faculty.washington.edu/marilynr/.

In addition to the subsection of QUINOLONES currently five families of qnr genes have been reported; qnrA (7 subtypes), qnrB (59 subtypes), qnrC (1 subtype), qnrD (1 subtype), and qnrS (8 subtypes) (Jacoby et al., 2008; Cattoir and Nordmann, 2009; Cavaco et al., 2009; Strahilevitz et al., 2009; Torpdahl et al., 2009).

Another mechanism of conferring resistance to quinolones is represented by the plasmid-borne gene qepA, which codes for an efflux pump that can export hydrophilic fluoroquinolones, e.g., ciprofloxacin and enrofloxacin (Périchon et al., 2007; Yamane et al., 2007). A variant of this resistance pump, QepA2, was identified in an E. coli isolate from France (Cattoir et al., 2008).

Regarding TETRACYCLINE, Resistance mechanisms, currently there are 45 different acquired tetracycline resistance determinants recognized (Roberts, 1996, 2005; Brown et al., 2008) (Table 6). For an up-to-date list of the acquired tetracycline resistance genes, we refer to the website of Dr. Marilyn Roberts, http://faculty.washington.edu/marilynr/. Among these, 26 of the tet genes, 2 of the otr genes and the only tcr determinant code for efflux pumps, whereas 11 tet genes and 1 otr gene code for ribosomal protection proteins (RPPs). The enzymatic inactivation mechanism can be attributed to 3 tet genes. The tet(U) determinant represents an unknown tetracycline resistance mechanism since its sequence does not appear to be related to either efflux or RPPs, nor to the inactivation enzymes. The efflux and RPP encoding genes are found in members of Gram-positive, Gram-negative, aerobic, as well as anaerobic bacteria. In contrast, the enzymatic tetracycline inactivation mechanism has so far only been identified in Gram-negative bacteria. The tet(M) has the broadest host range of all tetracycline resistance genes, whereas tet(B) gene has the widest range among the Gram-negative bacteria. In recent years published data indicate that there are increasing numbers of Gram-negative bacteria that carry tet genes originally identified in Gram-positive bacteria (Roberts, 2002).

To the subsection TRIMETHOPRIM, Resistance mechanisms. Initially, the acquired DHFRs fell into two distinct families A and B, encoded by the dfrA and dfrB genes (Howell, 2005). Up to now 6 plasmid-mediated families can be distinguished with relatively few dfr determinants originating from Gram-positive bacteria (Table 7). The dfrK and dfrA28 genes are the newest additions to the trimethoprim resistance determinant family (Kadlec and Schwarz, 2009; Kadlec et al., 2011). In contrast to the latest reported DHFRs, the oldest families, dfrA and dfrB, each contain several members (Roberts, 2002; Levings et al., 2006). For example, the dfrA group accomodates over 30 published genes; however, unpublished, dfrA variants are also present in the public DNA libraries and some genes apparently have changed nomenclature (Table 7).

Furthermore, we suggest an additional section concerning oxazolidinones.

Oxazolidinones

History and action mechanism

Linezolid is to date the only FDA-approved oxazolidinone (Shaw and Barbachyn, 2011). It was approved in 2000 for the treatment of serious infections caused by Gram-positive bacteria resistant to other antibiotics, such as vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) (Long and Vester, 2012). As such linezolid is considered one of the last resort antimicrobial agents in human medicine. It has not been approved for use in veterinary medicine. Oxazolidinones bind at the P site of the ribosome and inhibit the formation of the initiation complex, which consists of mRNA, f-Met tRNA, and the 50S ribosomal subunit (Shaw and Barbachyn, 2011; Long and Vester, 2012).

Resistance mechanism

Various mutations located in the peptidyl transferase loop of domain V of 23S rRNA as well as mutations in the genes for the ribosomal proteins L3 and L4, all associated with resistance to oxazolidinones, have been identified (reviewed by Long and Vester, 2012). A single gene, cfr, has been identified to confer transferable resistance to oxazolidinones. This gene codes for a methyltransferase that targets A2503 in 23S rRNA (Kehrenberg et al., 2005). Besides oxazolidinone resistance, it also confers resistance to phenicols, lincosamides, pleuromutilins, and streptogramin A antibiotics. Although initially identified in coagulase-negative staphylococci of animal origin, the gene cfr has now been detected in a wide variety of staphylococci of human and animal origin, including a Panton-Valentin leukocidin-positive MRSA USA300 (Shore et al., 2010) and livestock-associated MRSA ST398 (Kehrenberg et al., 2009). More recently, the cfr gene has also been identified in Bacillus spp. (Dai et al., 2010) and Enterococcus faecalis (Liu et al., 2012), but also in Gram-negative bacteria, such as Proteus vulgaris (Wang et al., 2011) and Escherichia. coli (Wang et al., 2012). Plasmids and insertion sequences seem to play an important role in the spread of this gene across species and genus boundaries.