Muramyl endopeptidase Spr contributes to intrinsic vancomycin resistance in Salmonella enterica serovar Typhimurium
Muramyl endopeptidase Spr contributes to intrinsic vancomycin resistance in Salmonella enterica serovar Typhimurium
ABSTRACT 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 mepA, pbpG, nlpC, yebA or yhdO genes coding for functional homologues to Spr. The spr mutant revealed 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 an 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 that target specific cell wall endopeptidases might have the potential to expand the activity spectrum of traditional Gram-positive antibiotics.
Huseby Douglas L、Iina Snygg、Rhen Mikael、Wang Helen、Vest? Kim、Hughes Diarmaid
Department of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet||Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), and Ume? Centre for Microbial Research (UCMR), Ume? UniversityDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Medical Biochemistry and Microbiology, Uppsala University
微生物学生物化学药学
Huseby Douglas L,Iina Snygg,Rhen Mikael,Wang Helen,Vest? Kim,Hughes Diarmaid.Muramyl endopeptidase Spr contributes to intrinsic vancomycin resistance in Salmonella enterica serovar Typhimurium[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/274886.点此复制
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