Abstract 2942 Breaking Down Barriers: Unraveling Van A Resistance

Enterococcus faecium and Enterococcus faecalis are opportunistic pathogens with broad antibiotic resistance that pose a serious threat to human health.These pathogens are prevalent in hospital environments, where they cause bloodstream infections, soft-tissue infections, and urinary tract infections, primarily in immunocompromised patients who have undergone extensive prior antibiotic treatment.The combined antibiotic resistance and opportunistic nature of E. faecium and E. faecalis amplify their danger, targeting vulnerable populations and severely limiting effective treatment options.E. faecium and E. faecalis are the leading causes of hospitalacquired infections.Infections from E. faecium are rising, with 52% of isolates resistant to vancomycin and 83% resistant to ampicillin.These trends underscore the urgent need to understand the mechanism of intrinsic antibiotic resistance of enterococci.Enterococci possess class B penicillin-binding proteins (bPBPs), which crosslink peptidoglycan in the final steps of peptidoglycan wall synthesis.One such bPBP in E. faecalis, penicillin-binding protein 4 (Pbp4), has been shown to demonstrate low reactivity to cephalosporins and is required for cephalosporin resistance.The structure of Pbp4 consists of a transmembrane domain, pedestal domain, non-penicillin binding domain, and transpeptidase (TPase) domain.The TPase domain contains the nucleophilic serine which catalyzes the formation of mature peptidoglycan and is also the target of beta-lactam antibiotics.Mutations in the TPase domain can lead to beta-lactam resistance.Through structural and biochemical approaches, understanding Pbp4 may lead to an increased understanding of antibiotic resistance mechanisms in E. faecalis and the development of novel antibiotics.