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Muramyl Endopeptidase Spr Contributes to Intrinsic Vancomycin Resistance in Salmonella enterica Serovar Typhimurium
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2018 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, article id 2941Article in journal (Refereed) Published
Abstract [en]

The impermeability barrier provided by the outer membrane of enteric bacteria, a feature lacking in Gram-positive bacteria, plays a major role in maintaining resistance to numerous antimicrobial compounds and antibiotics. Here we demonstrate that mutational inactivation of spr, coding for a muramyl endopeptidase, significantly sensitizes Salmonella enterica serovar Typhimurium to vancomycin without any accompanying apparent growth defect or outer membrane destabilization. A similar phenotype was not achieved by deleting the genes coding for muramyl endopeptidases MepA, PbpG, NlpC, YedA, or YhdO. The spr mutant showed increased autolytic behavior in response to not only vancomycin, but also to penicillin G, an antibiotic for which the mutant displayed a wild-type MIC. A screen for suppressor mutations of the spr mutant phenotype revealed that deletion of tsp (prc), encoding a periplasmic carboxypeptidase involved in processing Spr and PBP3, restored intrinsic resistance to vancomycin and reversed the autolytic phenotype of the spr mutant. Our data suggest that Spr contributes to intrinsic antibiotic resistance in S. Typhimurium without directly affecting the outer membrane permeability barrier. Furthermore, our data suggests that compounds targeting specific cell wall endopeptidases might have the potential to expand the activity spectrum of traditional Gram-positive antibiotics.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018. Vol. 9, article id 2941
Keywords [en]
vancomycin, antibiotic resistance, Spr, MepS, YebA, MepM, Tsp, Prc
National Category
Microbiology
Identifiers
URN: urn:nbn:se:umu:diva-154867DOI: 10.3389/fmicb.2018.02941ISI: 000453344700001OAI: oai:DiVA.org:umu-154867DiVA, id: diva2:1275232
Note

Errata: Vestö K, Huseby DL, Snygg I, Wang H, Hughes D and Rhen M (2019) Corrigendum: Muramyl Endopeptidase Spr Contributes to Intrinsic Vancomycin Resistance in Salmonella enterica Serovar Typhimurium. Front. Microbiol. 10:386. doi: 10.3389/fmicb.2019.00386

Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-04-02Bibliographically approved

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Rhen, Mikael

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Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)
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CiteExportLink to record
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