Potentiating hypoxic microenvironment for antibiotic activation by photodynamic therapy to combat bacterial biofilm infections

Weijun Xiu, Ling Wan, Kaili Yang, Xiao Li, Lihui Yuwen (), Heng Dong, Yongbin Mou, Dongliang Yang and Lianhui Wang ()
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Weijun Xiu: Nanjing University of Posts and Telecommunications
Ling Wan: Nanjing University of Posts and Telecommunications
Kaili Yang: Nanjing University of Posts and Telecommunications
Xiao Li: Nanjing University of Posts and Telecommunications
Lihui Yuwen: Nanjing University of Posts and Telecommunications
Heng Dong: Medicine School of Nanjing University
Yongbin Mou: Medicine School of Nanjing University
Dongliang Yang: Nanjing Tech University
Lianhui Wang: Nanjing University of Posts and Telecommunications

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide alternative therapeutic routes. In this study, photodynamic therapy is used not only to eradicate methicillin-resistant Staphylococcus aureus biofilms in the normoxic condition, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of methicillin-resistant Staphylococcus aureus and activates the antibacterial activity of metronidazole. Moreover, the photodynamic therapy-activated chemotherapy can polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize photodynamic therapy with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections.

Date: 2022
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DOI: 10.1038/s41467-022-31479-x

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