TY - JOUR
T1 - Identification of a potent indigoid persister antimicrobial by screening dormant cells
AU - Song, Sooyeon
AU - Gong, Ting
AU - Yamasaki, Ryota
AU - Kim, Jun Seob
AU - Wood, Thomas K.
N1 - Funding Information:
This study was supported by funds derived from the Biotechnology Endowed Professorship at the Pennsylvania State University (for T. K. W.) and the KRIBB Initiative Research Program (for J. S. K.).
Funding Information:
This study was supported by funds derived from the Biotechnology Endowed Professorship at the Pennsylvania State University (for T. K. W.) and the KRIBB Initiative Research Program (for J. S. K.).
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/9
Y1 - 2019/9
N2 - 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-1H-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.
AB - 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-1H-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.
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U2 - 10.1002/bit.27078
DO - 10.1002/bit.27078
M3 - Article
C2 - 31161664
AN - SCOPUS:85070852358
SN - 0006-3592
VL - 116
SP - 2263
EP - 2274
JO - Biotechnology and bioengineering
JF - Biotechnology and bioengineering
IS - 9
ER -