期刊
GENE
卷 358, 期 -, 页码 82-92出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2005.05.027
关键词
antibiotic resistance; ampC; chromosomal class D beta-lactamase
资金
- NIGMS NIH HHS [S06 GM08205] Funding Source: Medline
Pseudomonas aeruginosa is the major pathogen associated with morbidity and mortality of patients with cystic fibrosis. One of the reasons for the failure of beta-lactam antibiotic regimens appears to be mediated by de-regulation of the ampC gene, encoding the chromosomal Ambler's Class beta-lactamase. Currently, the AmpC is the only known chromosomal beta-lactamase whose expression is regulated by a transcriptional regulator, AmpR. We generated an ampC mutation in the prototypic R aeruginosa strain PAO1. The mutation in ampC did not abolish the beta-lactamase activity entirely suggesting the expression of yet another unreported beta-lactamase. Our genomic analysis revealed the presence of an open reading frame encoding a protein with high homology to the Class D beta-lactamases, commonly known as oxacillinases. The gene was named poxB for Pseudomonas oxacillinase. Cloning and expression of poxB in Escherichia coli conferred beta-lactain resistance to the host. We detected the presence of poxB both in clinical and environmental isolates. Our studies show that R aeruginosa possesses two beta-lactamases, AmpC and PoxB, which contribute to its resistance against a wide spectrum of beta-lactam antibiotics. (C) 2005 Elsevier B.V. All rights reserved.
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