The G132S Mutation Enhances the Resistance of Mycobacterium tuberculosis β-Lactamase against Sulbactam.

ABSTRACT: The current rise of antibiotic resistant forms of Mycobacterium tuberculosis is a global health threat that calls for new antibiotics. The β-lactamase BlaC of this pathogen prevents the use of β-lactam antibiotics, except in combination with a β-lactamase inhibitor. To understand if exposure to such inhibitors can easily result in resistance, a BlaC evolution experiment was performed, studying the evolutionary adaptability against the inhibitor sulbactam. Several amino acid substitutions in BlaC were shown to confer reduced sensitivity to sulbactam. The G132S mutation causes a reduction in the rate of nitrocefin and ampicillin hydrolysis and simultaneously reduces the sensitivity for sulbactam inhibition. Introduction of the side chain moiety of Ser132 causes the 104-105 peptide bon

SUBMITTER: van Alen I 

PROVIDER: S-EPMC8383266 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature