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DNA‐crosslinker cisplatin eradicates bacterial persister cells
Author(s) -
Chowdhury Nityananda,
Wood Thammajun L.,
MartínezVázquez Mariano,
GarcíaContreras Rodolfo,
Wood Thomas K.
Publication year - 2016
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25963
Subject(s) - multidrug tolerance , cisplatin , microbiology and biotechnology , pseudomonas aeruginosa , antibiotics , antimicrobial , staphylococcus aureus , escherichia coli , bacteria , biology , mitomycin c , chemistry , biofilm , biochemistry , chemotherapy , genetics , gene
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.