Premium
Identification of a potent indigoid persister antimicrobial by screening dormant cells
Author(s) -
Song Sooyeon,
Gong Ting,
Yamasaki Ryota,
Kim JunSeob,
Wood Thomas K.
Publication year - 2019
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.27078
Subject(s) - multidrug tolerance , staphylococcus aureus , pseudomonas aeruginosa , microbiology and biotechnology , cisplatin , escherichia coli , antimicrobial , bacteria , chemistry , lysis , biology , biochemistry , biofilm , chemotherapy , gene , genetics
The subpopulation of bacterial cells that survive myriad stress conditions (e.g., nutrient deprivation and antimicrobials) by ceasing metabolism, revive by activating ribosomes. These resuscitated cells can reconstitute infections; hence, it is imperative to discover compounds which eradicate persister cells. By screening 10,000 compounds directly for persister cell killing, we identified 5‐nitro‐3‐phenyl‐1 H ‐indol‐2‐yl‐methylamine hydrochloride (NPIMA) kills Escherichia coli persister cells more effectively than the best indigoid found to date, 5‐iodoindole, and better than the DNA‐crosslinker cisplatin. In addition, NPIMA eradicated Pseudomonas aeruginosa persister cells in a manner comparable to cisplatin. NPIMA also eradicated Staphylococcus aureus persister cells but was less effective than cisplatin. Critically, NPIMA kills Gram‐positive and Gram‐negative bacteria by damaging membranes and causing lysis as demonstrated by microscopy and release of extracellular DNA and protein. Furthermore, NPIMA was effective in reducing P. aeruginosa and S. aureus cell numbers in a wound model, and no resistance was found after 1 week. Hence, we identified a potent indigoid that kills persister cells by damaging their membranes.