In silico assigned resistance genes confer Bifidobacterium with partial resistance to aminoglycosides but not to β-lactams

dc.contributor.authorFouhy, Fiona
dc.contributor.authorO'Connell Motherway, Mary
dc.contributor.authorFitzgerald, Gerald F.
dc.contributor.authorRoss, R. Paul
dc.contributor.authorStanton, Catherine
dc.contributor.authorvan Sinderen, Douwe
dc.contributor.authorCotter, Paul D.
dc.contributor.funderIrish Research Council for Science Engineering and Technology
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderHealth Research Board
dc.description.abstractBifidobacteria have received significant attention due to their contribution to human gut health and the use of specific strains as probiotics. It is thus not surprising that there has also been significant interest with respect to their antibiotic resistance profile. Numerous culture-based studies have demonstrated that bifidobacteria are resistant to the majority of aminoglycosides, but are sensitive to β-lactams. However, limited research exists with respect to the genetic basis for the resistance of bifidobacteria to aminoglycosides. Here we performed an in-depth in silico analysis of putative Bifidobacterium-encoded aminoglycoside resistance proteins and β-lactamases and assess the contribution of these proteins to antibiotic resistance. The in silico-based screen detected putative aminoglycoside and β-lactam resistance proteins across the Bifidobacterium genus. Laboratory-based investigations of a number of representative bifidobacteria strains confirmed that despite containing putative β-lactamases, these strains were sensitive to β-lactams. In contrast, all strains were resistant to the aminoglycosides tested. To assess the contribution of genes encoding putative aminoglycoside resistance proteins in Bifidobacterium sp. two genes, namely Bbr_0651 and Bbr_1586, were targeted for insertional inactivation in B. breve UCC2003. As compared to the wild-type, the UCC2003 insertion mutant strains exhibited decreased resistance to gentamycin, kanamycin and streptomycin. This study highlights the associated risks of relying on the in silico assignment of gene function. Although several putative β-lactam resistance proteins are located in bifidobacteria, their presence does not coincide with resistance to these antibiotics. In contrast however, this approach has resulted in the identification of two loci that contribute to the aminoglycoside resistance of B. breve UCC2003 and, potentially, many other bifidobacteria.en
dc.description.sponsorshipIrish Research Council for Science Engineering and Technology (EMBARK Scholarship); Teagasc (Walsh Fellowship); Science Foundation Ireland (Grant Nos.11/PI/1137; 07/CE/B1368; 02/CE/B124); Health Research Board (Postdoctoral Fellowship PDTM/20011/9)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationFouhy F, O’Connell Motherway M, Fitzgerald GF, Ross RP, Stanton C, van Sinderen D, et al. (2013) In Silico Assigned Resistance Genes Confer Bifidobacterium with Partial Resistance to Aminoglycosides but Not to Β-Lactams. PLoS ONE 8(12): e82653. doi:10.1371/journal.pone.0082653
dc.identifier.journaltitlePLOS ONEen
dc.publisherPublic Library of Scienceen
dc.rights© 2015 Fouhy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
dc.subjectSusceptibility testing methoden
dc.subjectBile salt hydrolaseen
dc.subjectAntimicrobial susceptibilityen
dc.subjectAntibiotic resistanceen
dc.subjectBreve UCC2003en
dc.subjectBacterial resistanceen
dc.subjectFunctional characterizationen
dc.subjectGenome annotationen
dc.subjectStrain Yakulten
dc.titleIn silico assigned resistance genes confer Bifidobacterium with partial resistance to aminoglycosides but not to β-lactamsen
dc.typeArticle (peer-reviewed)en
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Additional File 1: Table S1.