Multi-roles of nanoscale bismuth metal-organic frameworks: Infectious photoacoustic probe and inhibitor of antibiotics tolerant bacteria via targeting endogenous H2S

Increasing evidence has emphasized the pivotal role of antibiotic tolerance in the evolution of antibiotic resistance, refractory infection and infection recurrence. Moreover, satisfactory treatment of infection relies highly on early, precise detection and subsequent timely therapeutic interventions. In this study, the phenotype of increased production of H2S in antibiotic-tolerant Staphylococcus aureus (S. aureus) was identified and proven to be essential to the maintenance of antibiotic tolerance. Hence, a photoacoustic probe for detecting infection as well as an antibiotic enhancer targeting bacterial endogenous H2S to eradicate antibiotic-tolerant bacteria was successfully developed based on a bismuth metal-organic framework (Bi-MOF). Bi-MOF achieved early in situ and precise photoacoustic imaging of infection by generating Bi2S3 inside bacteria. Moreover, Bi-MOF enhanced the eradication efficacy of methicillin against tolerant S. aureus by downregulating the intracellular H2S levels. Overall, Bi-MOF offers a promising diagnostic tool for early, precise infection diagnosis and a therapeutic strategy for tolerant bacteria-related refractory infection. [Display omitted] •Bi-MOF breaks down the antibiotic-tolerance by targeting endogenous H2S.•Bi-MOF realizes in-situ photoacoustic imaging diagnosis by precipitating bacterial H2S.•Multi-omics analysis reveals the metabolic mobolization and proteotoxicity effects of the Bi-MOF.•Bi-MOF cooperates with methicillin to prevent the recurrence of tolerant S. aureus-related infection.•Antibiotic-tolerant S. aureus upregulates H2S production to defend against antibiotics.