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 H 2 S 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 H 2 S 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 Bi 2 S 3 inside bacteria. Moreover, Bi-MOF enhanced the eradication efficacy of methicillin against tolerant S. aureus by downregulating the intracellular H 2 S levels. Overall, Bi-MOF offers a promising diagnostic tool for early, precise infection diagnosis and a therapeutic strategy for tolerant bacteria-related refractory infection.