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 because of the low susceptibility of the bacteria involved to antibiotics and high incidence of recurrent infections. Methods: Herein, a photosynthetic bacteria-based multiplex system composed of natural Rhodopseudomonas palustris (Rp) and Food and Drug Administration-approved aluminum adjuvant (Rp@Al), was developed to combat drug-resistant bacterial infections and prevent their recurrence. We examined its photothermal performance, in vitro and in vivo antibacterial ability; revealed its protective immunomodulatory effect; verified its prevention effect on recurrent infections; demonstrated the system safety. Results: Rp@Al exhibits excellent photothermal properties with an effective elimination of methicillin-resistant Staphylococcus aureus (MRSA). In addition, Rp@Al elicits the activation of dendritic cells 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.