VanG- and D-Ala-D-Ser-dependent peptidoglycan synthesis and vancomycin resistance in Clostridioides difficile.

ABSTRACT: A Clostridioides difficile strain deficient in the ddl gene is unable to synthesize the dipeptide D-Ala-D-Ala, an essential component of peptidoglycan and the target of vancomycin. We isolated spontaneous suppressors of a ∆ddl mutation that allowed cell growth in the absence of D-Ala-D-Ala. The mutations caused constitutive or partly constitutive expression of the vancomycin-inducible vanG operon responsible for the synthesis of D-Ala-D-Ser, which can replace D-Ala-D-Ala in peptidoglycan. The mutations mapped to the vanS or vanR genes, which regulate expression of the vanG operon. The constitutive level of vanG expression was about 10-fold above that obtained by vancomycin induction. The incorporation of D-Ala-D-Ser into peptidoglycan due to high expression of the vanG operon conferred onl

SUBMITTER: Belitsky BR 

PROVIDER: S-EPMC9671823 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature