A glycine at position 105 leads to clavulanic acid and avibactam resistance in class A β-lactamases.

ABSTRACT: β-Lactamase enzymes exhibit extraordinary adaptive potential, thus rendering many β-lactam drugs ineffective. The residue at Ambler position 105, also known as the gatekeeper residue, plays an important role in substrate recognition, but its implication in inhibition mechanisms remains understudied and obscure. To inspect the relationship between inhibitor-resistant phenotypes and residues at this position, we performed site-saturation mutagenesis and extensive fitness profiling of five distinct class A β-lactamases using deep sequencing. We found that inhibitor resistance is readily detectable, with variants harboring Gly or Arg being the least susceptible to inhibitors. Mutation of Ile105 to Arg in the β-lactamase BlaC simultaneously enhances activity for carbenicillin and the ability to

SUBMITTER: Radojkovic M 

PROVIDER: S-EPMC12274840 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature