Bacteria-based multiplex system eradicates recurrent infections with drug-resistant bacteria via photothermal killing and protective immunity elicitation

Abstract

Background: The high mortality associated with drug-resistant bacterial infections is an intractable clinical problem resulting from the low susceptibility of these bacteria to antibiotics and the high incidence of recurrent infections. Methods: Herein, a photosynthetic bacteria-based multiplex system (Rp@Al) composed of natural Rhodopseudomonas palustris (Rp) and Food and Drug Administration-approved aluminum (Al) adjuvant, was developed to combat drug-resistant bacterial infections and prevent their recurrence. We examined its photothermal performance and in vitro and in vivo antibacterial ability; revealed its protective immunomodulatory effect; verified its preventative effect on recurrent infections; and demonstrated the system’s safety. Results: Rp@Al exhibits excellent photothermal properties with an effective elimination of methicillin-resistant Staphylococcus aureus (MRSA). In addition, Rp@Al enhances dendritic cell activation and further triggers a T helper 1 (TH1)/TH2 immune response, resulting in pathogen-specific immunological memory against recurrent MRSA infection. Upon second infection, Rp@Al-treated mice show significantly lower bacterial burden, faster abscess recovery, and higher survival under near-lethal infection doses than control mice. Conclusions: This innovative multiplex system, with superior photothermal and immunomodulatory effects, presents great potential for the treatment and prevention of drug-resistant bacterial infections. Graphical Abstract: [Figure not available: see fulltext.]