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Potential of bacteriophage therapy in managing Staphylococcus aureus infections during chemotherapy for lung cancer
Jiaqi Li1, Huangliang Zheng1, Sharon Shui Yee Leung2
1School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong.
Abstract:
Respiratory Staphylococcus aureus infection represents a common complication in lung cancer patients, which is characterized with progressively and recurrently intratumor invasion. Although bacteriophages are widely reported as an effective bioweapon for managing bacterial infections, its applicability in handling infectious complications during cancer chemotherapy remains unknown. In this work, we hypothesized cancer chemotherapeutics would influence the efficacy of bacteriophages. To verify this end, interactions between four anticancer drugs (Gemcitabine, Doxorubicin, Cisplatin, and Irinotecan) with phage K were investigated, where Cisplatin directly reduced phage titers while Gemcitabine and Doxorubicin partially inhibited its propagation. The antibacterial efficacy of drug-phage K combinations was tested in a S. aureus infected cancer cell model. Doxorubicin enhanced the antibacterial capacity of phage K, destroying 22-folds of cell-associated bacteria than that of phage K alone use. Also, S. aureus migration was remarkably reduced by Doxorubicin. Overall, our data suggested that Doxorubicin had synergistic effects with phage K in combating S. aureus intracellular infection and migration. This work may broaden the options of indication for phage clinical transformation and also provide reference for the adjunctive application of chemo drugs in intracellular infection management.
Insights
This study explored how chemotherapy drugs affect bacteriophage efficacy against Staphylococcus aureus lung infections in cancer patients. Doxorubicin showed synergistic effects with phage K, enhancing bacterial clearance and reducing migration.
Area of Science:
- Bacteriology
- Oncology
- Antimicrobial Therapy
Background:
- Respiratory Staphylococcus aureus infections are common and invasive in lung cancer patients.
- The use of bacteriophages to manage bacterial infections during cancer chemotherapy is largely unexplored.
- Anticancer drugs may impact bacteriophage efficacy, necessitating investigation into their interactions.
Purpose of the Study:
- To investigate the influence of common chemotherapeutic agents on bacteriophage K activity.
- To evaluate the combined efficacy of phage K and anticancer drugs against Staphylococcus aureus in a cancer cell model.
- To determine if Doxorubicin enhances phage K's ability to combat intracellular S. aureus infection and migration.
Main Methods:
- Tested interactions between phage K and four anticancer drugs: Gemcitabine, Doxorubicin, Cisplatin, and Irinotecan.
- Assessed direct effects on phage titers and propagation.
- Evaluated antibacterial efficacy of drug-phage K combinations in a Staphylococcus aureus-infected cancer cell model.
Main Results:
- Cisplatin reduced phage titers, while Gemcitabine and Doxorubicin partially inhibited phage propagation.
- Doxorubicin significantly enhanced phage K's antibacterial capacity, achieving 22-fold greater bacterial destruction compared to phage K alone.
- Doxorubicin notably reduced Staphylococcus aureus migration and demonstrated synergistic effects with phage K against intracellular infections.
Conclusions:
- Doxorubicin exhibits synergistic effects with phage K against intracellular Staphylococcus aureus infections and migration in a cancer cell model.
- This research suggests potential for phage therapy as an adjunct to chemotherapy for managing bacterial complications in cancer patients.
- Findings provide a basis for expanding phage clinical applications and inform the adjunctive use of chemotherapy drugs in managing intracellular infections.
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