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Combating Multiple-Drug Resistance Polymicrobial Biofilm Infections with an Amphiphilic Cationic Photosensitizer
Hu Gao1,2,3, Bing-Wei Guo4, Yuan Chen5,6
1Department of Emergency, West China Second University Hospital, Sichuan University, 610041 Chengdu, Sichuan, P. R. China.
Abstract:
Polymicrobial infections, particularly those involving both Gram-positive (G+) and Gram-negative (G-) bacteria, present a severe public health threat due to the lack of effective treatments. The formation of polymicrobial biofilms further complicate this challenge, underscoring the urgent need for innovative therapeutic strategies. To address this issue, we designed a series of amphiphilic cationic photosensitizers (PSs) featuring distinct hydrophilic cationic side chains (pyridinium, imidazolium, alkyl quaternary ammonium, and quaternary phosphonium) and systematically investigated their structure-activity relationships. Among them, the pyridinium-modified PS, TBTCP-PY, demonstrated a superior performance. It efficiently generates hydroxyl radicals (•OH) and singlet oxygen (1O2) upon light irradiation, enabling it to target and disrupt the membranes of both G+ and G- bacteria. Furthermore, TBTCP-PY exhibits a strong capacity to penetrate extracellular polymeric substances (EPS), leading to the effective eradication of polymicrobial biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA). In a murine model, TBTCP-PY successfully eliminated MRSA-MDR-PA polymicrobial biofilms from implanted medical catheters, reduced subsequent inflammation, and promoted wound healing. This work not only presents a promising candidate for treating complex polymicrobial biofilm infections but also provides valuable theoretical insights into developing novel antibiofilm materials.
Insights
A novel pyridinium-based photosensitizer effectively eradicated polymicrobial biofilms, including MRSA and MDR-PA, by generating reactive oxygen species. This offers a promising new strategy for treating challenging bacterial infections and promoting wound healing.
Area of Science:
- Photodynamic therapy
- Antimicrobial materials science
- Infectious disease research
Background:
- Polymicrobial infections and biofilms pose significant treatment challenges.
- Existing therapies are often ineffective against mixed bacterial populations and biofilms.
- Novel strategies are urgently needed to combat these threats.
Purpose of the Study:
- To design and evaluate amphiphilic cationic photosensitizers (PSs) for treating polymicrobial infections.
- To investigate the structure-activity relationships of different cationic side chains in PSs.
- To identify a potent PS capable of eradicating biofilms and promoting healing.
Main Methods:
- Synthesis of amphiphilic cationic PSs with varying side chains (pyridinium, imidazolium, etc.).
- Evaluation of photosensitizing properties, including reactive oxygen species generation (•OH, 1O2).
- Assessment of biofilm penetration and eradication capabilities against MRSA and MDR-PA.
- In vivo testing in a murine model with infected medical catheters.
Main Results:
- The pyridinium-modified PS, TBTCP-PY, showed superior performance.
- TBTCP-PY efficiently generated hydroxyl radicals and singlet oxygen upon light irradiation.
- It effectively penetrated extracellular polymeric substances (EPS) to eradicate MRSA-MDR-PA biofilms.
- In vivo studies demonstrated biofilm elimination, reduced inflammation, and enhanced wound healing.
Conclusions:
- TBTCP-PY is a promising candidate for treating complex polymicrobial biofilm infections.
- The study provides theoretical insights for developing novel antibiofilm materials.
- This approach offers a new avenue for combating antibiotic-resistant bacterial infections.
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