title: 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.
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park, 16802-4400, Pennsylvania.
authors.forename: Nityananda
authors.initials: N
authors.lastname: Chowdhury
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park, 16802-4400, Pennsylvania.
authors.forename: Thammajun L
authors.initials: TL
authors.lastname: Wood
authors.affiliation: Laboratorio de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, México.
authors.forename: Mariano
authors.initials: M
authors.lastname: Martínez-Vázquez
authors.affiliation: Faculty of Medicine, Department of Microbiology and Parasitology, Universidad Nacional Autónoma de México, México.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: García-Contreras
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park, 16802-4400, Pennsylvania. twood@engr.psu.edu.|Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania. twood@engr.psu.edu.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D004247:DNA; D002945:Cisplatin
keywords: DNA-crosslinking; biofilm; cisplatin; persistence