Adaptation of Bacteria to Antineoplastic Agents Involves Persister Cells and Increases Resistance to Antibiotics

Abstract

The increasing number of life-threatening infections observed in cancer patients has been ascribed to chemotherapy-induced neutropenia and to invasive medical procedures such as surgery and the application of catheters. In this study, it was questioned if the infections could also be favored by an increased resistance of bacteria due to the adaptation to antineoplastic agents used in chemotherapy. After exposure to several antineoplastic agents, it was observed that cells of Staphylococcus aureus, Mycobacterium vaccae, Pseudomonas aeruginosa, and Escherichia coli changed the fatty acid profile of their cellular membranes, produced exopolymeric substances, and formed aggregates that adhered to surfaces. Additionally, when exposed to high concentrations of these compounds, a persister sub-population could be identified. After adaptation to antineoplastic agents, the minimum inhibitory concentration (MIC) of several antibiotics increased considerably in the tested strains.

Keywords

• mitomycin C
• cyclophosphamide
• etoposide
• methotrexate
• cancer
• tolerance