Bacterial Infections and Their Cell Wall Ligands Differentially Modulate Doxorubicin Sensitivity in Triple-Negative...

Area of Science:

• Microbiology
• Oncology
• Immunology

Background:

• Triple-negative breast cancer (TNBC) is aggressive with poor outcomes.
• The tumor microbiome may impact TNBC progression and treatment response.

Purpose of the Study:

• Investigate how Pseudomonas aeruginosa and Staphylococcus aureus, and their cell wall components (LPS, LTA), affect doxorubicin (DOX) efficacy in TNBC cells.
• Assess bacterial uptake, persistence, and impact on drug response in TNBC cell lines.

Main Methods:

• Utilized gentamicin protection assays to quantify bacterial uptake and survival in TNBC cells.
• Employed flow cytometry and CFU counting to analyze bacterial presence and effects on DOX response.
• Tested the impact of bacterial infection and purified LPS/LTA on DOX accumulation and cytotoxicity.

Main Results:

• Both P. aeruginosa and S. aureus were internalized and persisted in TNBC cells variably.
• Bacterial infection and LPS/LTA significantly increased DOX accumulation and cytotoxicity in MDA-MB-468 and MDA-MB-231 cells.
• Toll-like receptor (TLR2 and TLR4) signaling is implicated in modulating drug uptake, as suggested by LPS/LTA effects.

Conclusions:

• Bacterial presence and components enhance doxorubicin uptake and cytotoxicity in specific TNBC cell lines.
• TLR signaling pathways are involved in mediating these effects.
• Host-microbe interactions are crucial in determining chemotherapy response in TNBC, warranting further research.