DNA‐crosslinker cisplatin eradicates bacterial persister cells
Abstract
For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA‐approved anti‐cancer drug cisplatin [cis‐diamminodichloroplatinum(II)], which mainly forms intra‐strand DNA crosslinks, eradicates Escherichia coli K‐12 persister cells through a growth‐independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter‐strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984–1992. © 2016 Wiley Periodicals, Inc.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 10, 2016
- Source ID
- 10.1002/bit.25963
Entities
People
- Mariano Martínez‐vázquez
- Nityananda Chowdhury
- Rodolfo García‐contreras
- Thammajun L. Wood
- Thomas K. Wood
Organizations
- Army Research Office
- National Autonomous University of Mexico
- Pennsylvania State University