Cephalosporinases associated with outer membrane vesicles released by Bacteroides spp. protect gut pathogens and commensals against beta-lactam antibiotics

Stentz, Régis, Horn, Nikki, Cross, Kathryn, Salt, Louise, Brearley, Charles ORCID: https://orcid.org/0000-0001-6179-9109, Livermore, David M. ORCID: https://orcid.org/0000-0002-9856-3703 and Carding, Simon R. (2015) Cephalosporinases associated with outer membrane vesicles released by Bacteroides spp. protect gut pathogens and commensals against beta-lactam antibiotics. Journal of Antimicrobial Chemotherapy, 70 (3). pp. 701-709. ISSN 0305-7453

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Abstract

Objectives: To identify β-lactamase genes in gut commensal Bacteroides species and to 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 (locus tag BT_4507) found in the genome of the human commensal Bacteroides 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 susceptibility 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 Bacteroides fragilis. OMVs produced by B. thetaiotaomicron and several other Bacteroides species, except Bacteroides ovatus, carried surface-associated β-lactamases that could degrade cefotaxime. β-Lactamase-harbouring OMVs from B. thetaiotaomicron protected Salmonella Typhimurium and B. breve from an otherwise lethal dose of cefotaxime. Conclusions: The production of membrane vesicles carrying surface-associated β-lactamases by Bacteroides species, which constitute a major part of the human colonic microbiota, may protect commensal bacteria and enteric pathogens, such as Salmonella Typhimurium, against β-lactam antibiotics.

Item Type:	Article
Additional Information:	© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:	β-lactamases,protective effect,gut microbiota,salmonella
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Groups > Plant Sciences Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User:	Pure Connector
Date Deposited:	21 Oct 2015 14:00
Last Modified:	21 Oct 2022 01:08
URI:	https://ueaeprints.uea.ac.uk/id/eprint/54735
DOI:	10.1093/jac/dku466

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