Resensitizing β-Lactams by Reprogramming Purine Metabolism in Small Colony Variant for Osteomyelitis Treatment.

ABSTRACT: Small colony variant (SCV) is strongly linked to antibiotic resistance and the persistence of osteomyelitis. However, the intrinsic phenotypic instability of SCV has hindered a thorough investigation of its pathogenic mechanisms. In this study, phenotypically stable SCV strains are successfully recovered from clinical specimens, characterized by elevated drug resistance and reduced immunogenicity. Multi-omics analysis revealed that the acquired high drug resistance is associated with altered flux in the purine metabolism pathway, attributable to mutations in the hypoxanthine phosphoribosyltransferase (hpt) gene. Furthermore, this study innovatively discovered that lonidamine, an inhibitor of cellular energy metabolism, can effectively mitigate SCV resistance to β-lactam antibiotics, thereb

SUBMITTER: Shi T 

PROVIDER: S-EPMC11791937 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature