Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus.

ABSTRACT: Antibiotic resistance in bacterial pathogens is an ongoing public health concern. The arylomycins are a class of natural product antibiotics that target the type I signal peptidase, which carries out the terminal step in protein secretion. Here, we used transposon sequencing (Tn-Seq) to profile the effects of the optimized arylomycin derivative G0775 in Staphylococcus aureus. Our transposon libraries include both upregulation and inactivation mutants, allowing us to identify resistance mechanisms and targets for synergism. We identified several cell envelope pathways that, when inactivated, sensitize S. aureus to the arylomycin G0775. These pathways include the lipoprotein processing pathway, and we have shown that inhibitors of this pathway synergize with G0775 even though lipoprotein pro

SUBMITTER: Stone MC 

PROVIDER: S-EPMC10190671 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature