A novel class A extended-spectrum beta-lactamase (BES-1) in Serratia marcescens isolated in Brazil.
Serratia marcescens Rio-5, one of 18 extended-spectrum beta-lactamase (ESBL)-producing strains isolated in several hospitals in Rio de Janeiro (Brazil) in 1996 and 1997, exhibited a high level of resistance to aztreonam (MIC, 512 microgram/ml) and a distinctly higher level of resistance to cefotaxime (MIC, 64 microgram/ml) than to ceftazidime (MIC, 8 microgram/ml). The strain produced a plasmid-encoded ESBL with a pI of 7.5 whose bla gene was not related to those of other plasmid-mediated Ambler class A ESBLs. Cloning and sequencing revealed a bla gene encoding a novel class A beta-lactamase in functional group 2be, designated BES-1 (Brazil extended-spectrum beta-lactamase). This enzyme had 51% identity with chromosomal class A penicillinase of Yersinia enterocolitica Y56, which was the most closely related enzyme and 47 to 48% identity with CTX-M-type beta-lactamases, which were the most closely related ESBLs. In common with CTX-M enzymes, BES-1 exhibited high cefotaxime-hydrolyzing activity (k(cat), 425 s(-1)). However, BES-1 differed from CTX-M enzymes by its significant ceftazidime-hydrolyzing activity (k(cat), 25 s(-1)), high affinity for aztreonam (K(i), 1 microM), and lower susceptibility to tazobactam (50% inhibitory concentration [IC(50)], 0.820 microM) than to clavulanate (IC(50), 0.045 microM). Likewise, certain characteristic structural features of CTX-M enzymes, such as Phe-160, Ser-237, and Arg-276, were observed for BES-1, which, in addition, harbored different residues (Ala-104, Ser-171, Arg-220, Gly-240) and six additional residues at the end of the sequence. BES-1, therefore, may be an interesting model for further investigations of the structure-function relationships of class A ESBLs.
Bonnet
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R
Laboratoire de Bactériologie, Faculté de Médecine, 63001 Clermont-Ferrand Cedex, France. Richard.Bonnet@u-clermont1.fr
Sampaio
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Chanal
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Sirot
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De Champs
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Viallard
J L
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Labia
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Sirot
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001938:Brazil; D003001:Cloning, Molecular; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012706:Serratia marcescens / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
D047090:beta-Lactams; C417322:beta-lactamase BES-1; D001618:beta-Lactamases