Affiliation:
1. Department of Pathology and Microbiology, University of Bristol, Bristol BS8 1TD, United Kingdom
2. the JONES Group/JMI Laboratories, North Liberty, Iowa
Abstract
ABSTRACT
SPM-1 is a new metallo-β-lactamase recently identified in
Pseudomonas aeruginosa
strain 48-1997A, isolated in Sao Paulo, Brazil. Kinetic analysis demonstrated that SPM-1 has a broad hydrolytic profile across a wide range of β-lactam antibiotics. Considerable variation was observed within the penicillin, cephalosporin, and carbapenem subfamilies; however, on the whole, SPM-1 appears to preferentially hydrolyze cephalosporins. The highest
k
cat/
K
m
ratios (in micromolar per second) overall were observed for this subgroup. The hydrolytic profile of SPM-1 bears the most similarity to that of the metallo-β-lactamase IMP-1, yet for the most part, SPM-1 has
k
cat
/
K
m
values higher than those of IMP-1. Zinc chelator studies established that progressive inhibition of SPM-1 by EDTA, dipicolinic acid, and 1-10-
o
-phenanthroline demonstrated a biexponential pattern in which none of the chelators completely inhibited SPM-1. A homology model of SPM-1 was developed on the basis of the IMP-1 crystal structure, which showed the protein folding and active-site structure characteristic of metallo-β-lactamases and which provides an explanation for the kinetic profiles observed.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference50 articles.
1. A novel integron-like element carrying the metallo-beta-lactamase gene blaIMP
2. Plasmid Location and Molecular Heterogeneity of the L1 and L2 β-Lactamase Genes of
Stenotrophomonas maltophilia
3. Bellais, S., S. Leotard, L. Poirel, T. Naas, and P. Nordmann. 1999. Molecular characterization of a carbapenem-hydrolyzing β-lactamase from Chryseobacterium (Flavobacterium) indologenes.FEMS Microbiol. Lett.171:127-132.
4. Genetic Diversity of Carbapenem-Hydrolyzing Metallo-β-Lactamases from
Chryseobacterium
(
Flavobacterium
)
indologenes
5. Bennett, P. M. 1999. Integrons and gene cassettes: a genetic construction kit for bacteria. J. Antimicrob. Chemother.43:1-4.
Cited by
59 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献