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

基于细菌的多重系统通过光热杀灭和保护性免疫引发消除耐药细菌的复发性感染

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作者:Youcui Xu #, Yi Wu #, Yi Hu #, Mengran Xu, Yanyan Liu, Yuting Ding, Jing Chen, Xiaowan Huang, Longping Wen, Jiabin Li, Chen Zhu

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.

Conclusions

This innovative multiplex system, with superior photothermal and immunomodulatory effects, presents great potential for the treatment and prevention of drug-resistant bacterial 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.

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