Sunday, August 12, 2012
Columbia Hall, Terrace Level (Washington Hilton)
β-lactamases are enzymes that inactivate β-lactam antibiotics such as the penicillins and the cephalosporins, thereby conferring resistance to certain β-lactams in bacteria that produce these proteins. Genes encoding β-lactamases are of clinical importance due to their presence and spread in certain pathogenic bacteria. In addition, β-lactamase encoding genes are sometimes present in bacteria that produce this class of antibiotic. It is generally accepted that certain antibiotic resistance genes evolved in producer organisms for self resistance, before being disseminated to pathogens. A β-lactamase like gene (blm) is located within the clavulanic acid gene cluster of Streptomyces clavuligerus, the producer of the β-lactam antibiotic cephamycin C and the well characterized β-lactamase inhibitor clavulanic acid. Clavulanic acid is used in combination with other β-lactam antibiotics to treat certain β-lactam resistant bacteria; therefore the presence of the blm gene within the clavulanic acid biosynthetic gene cluster is intriguing and warrants further study. The blm gene product (Blm) displays similarity to other class-A β-lactamases. Bioinformatics analysis suggests that Blm might possess a function other than β-lactamase activity due to the absence/modification of conserved residues found in the active sites of conventional β-lactamases. Our results show that although Blm possess relatively weak cephalosporinase activity, it might be somehow involved in clavulanic acid biosynthesis rather that self resistance to β-lactams produced by S. clavuligerus. Results from our most recent studies will be presented and their implications will be discussed.