Scientific Publications
Cephalosporinases associated with outer membrane vesicles released by Bacteroides spp. protect gut pathogens and commensals against β-lactam antibiotics
Journal of Antimicrobial Chemotherapy, 2015, doi:10.1093/jac/dku466
Objectives: To identify β-lactamase genes in gut commensal Bacteroides species and assess the impact of these enzymes, when carried by outer membrane vesicles (OMVs), in protecting enteric pathogens and commensals. Methods: A deletion mutant of the putative class A β-lactamase gene BT_4507 found in the genome of the human commensal B. thetaiotaomicron was constructed, and a phenotypic analysis performed. A phylogenetic tree was built from an alignment of nine Bacteroides cephalosporinase protein sequences, using the Maximum Likelihood method. The rate of cefotaxime degradation after incubation with OMVs produced by different Bacteroides species was quantified using a disc sensitivity test. The resistance of Salmonella Typhimurium and Bifidobacterium breve to cefotaxime in liquid culture in the presence of B. thetaiotaomicron OMVs was evaluated by measuring bacterial growth. Results: The B. thetaiotaomicron BT_4507 gene encodes a β-lactamase related to the CepA cephalosporinase of B. fragilis. OMVs produced by B. thetaiotaomicron BT_4507 and several other Bacteroides species, except B. ovatus, carried surface-associated β-lactamases that could degrade cefotaxime. β-Lactamase-harbouring OMVs from B. thetaiotaomicron protected S. Typhimurium and Bifid. breve from an otherwise lethal dose of cefotaxime. Conclusions: The production of membrane vesicles carrying surface-associated β-lactamases by Bacteroides spp. - which constitute a major part of the human colonic microbiota - may protect commensal bacteria and enteric pathogens such as S. Typhimurium against β-lactam antibiotics.
Journal of Antimicrobial Chemotherapy, 2015, doi:10.1093/jac/dku466
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