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J Antimicrob Chemother. 2015 Mar;70(3):701-9. doi: 10.1093/jac/dku466. Epub 2014 Nov 27.

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

Author information

1
Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK regis.stentz@ifr.ac.uk.
2
Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
3
Analytical Sciences Unit, Institute of Food Research, Norwich NR4 7UA, UK.
4
School of Biological Sciences, The University of East Anglia, Norwich NR4 7TJ, UK.
5
Norwich Medical School, The University of East Anglia, Norwich NR4 7TJ, UK.
6
Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK Norwich Medical School, The University of East Anglia, Norwich NR4 7TJ, UK.

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.

KEYWORDS:

Salmonella; gut microbiota; protective effect; β-lactamases

PMID:
25433011
PMCID:
PMC4319488
DOI:
10.1093/jac/dku466
[Indexed for MEDLINE]
Free PMC Article

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