Cancer chemotherapy as a driver for antibiotic resistance evolution (360G-Wellcome-213979_Z_18_Z)

Antibiotic resistance is one of the most urgent challenges in healthcare. The overuse and misuse of antibiotics has driven the evolution and spread of antibiotic resistance in bacteria, reducing the effectiveness of antibiotics that are currently available. Understanding how antibiotic resistance evolves and is selected for is crucial for developing strategies to counter this threat. Growing evidence shows that many therapeutic drugs commonly used in healthcare also have antibacterial effects, including several classes of cancer chemotherapy drug. Bacteria can become resistant to chemotherapy drugs through the same mechanisms used to develop resistance to antibiotics, and bacteria can carry chemotherapy resistance genes alongside antibiotic resistance genes on mobile genetic elements (MGEs) such as plasmids. This suggests that exposure to chemotherapy drugs contributes to the evolution and spread of antibiotic resistance. This study will interrogate cancer genome data and cancer patient gut metagenome data to assess the occurrence of chemotherapy resistance genes in bacteria from cancer patients, use experimental evolution under chemotherapy drug exposure to determine the ability of chemotherapy drugs to select for reduced susceptibility to antibiotics, and use a novel Hi-C method to determine the degree to which chemotherapy drugs promote the spread of MGEs that carry antibiotic resistance genes.