TY - JOUR
T1 - Halogenated indoles eradicate bacterial persister cells and biofilms
AU - Lee, Jin Hyung
AU - Kim, Yong Guy
AU - Gwon, Giyeon
AU - Wood, Thomas K.
AU - Lee, Jintae
N1 - Funding Information:
This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (#2015R1A2A2A01004542 to J. Lee), by the Basic Science Research Program through the NRF funded by the Ministry of Education (#215C000232 to J-H. Lee), and by the Priority Research Centers Program through the NRF funded by the Ministry of Education (#2014R1A6A1031189).
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/12/1
Y1 - 2016/12/1
N2 - The emergence of antibiotic resistance has necessitated new therapeutic approaches to combat recalcitrant bacterial infections. Persister cells, often found in biofilms, are metabolically dormant, and thus, are highly tolerant to all traditional antibiotics and represent a major drug resistance mechanism. In the present study, 36 diverse indole derivatives were investigated with the aim of identifying novel compounds that inhibit persisters and biofilm formation by Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. 5-Iodoindole and other halogenated indoles, 4-fluoroindole, 7-chloroindole, and 7-bromoindole, eradicated persister formation by E. coli and S. aureus, and 5-iodoindole most potently inhibited biofilm formation by the two bacteria. Unlike other antibiotics, 5-iodoindole did not induce persister cell formation, and 5-iodoindole inhibited the production of the immune-evasive carotenoid staphyloxanthin in S. aureus; hence, 5-iodoindole diminished the production of virulence factors in this strain. These results demonstrate halogenated indoles are potentially useful for controlling bacterial antibiotic resistance.
AB - The emergence of antibiotic resistance has necessitated new therapeutic approaches to combat recalcitrant bacterial infections. Persister cells, often found in biofilms, are metabolically dormant, and thus, are highly tolerant to all traditional antibiotics and represent a major drug resistance mechanism. In the present study, 36 diverse indole derivatives were investigated with the aim of identifying novel compounds that inhibit persisters and biofilm formation by Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. 5-Iodoindole and other halogenated indoles, 4-fluoroindole, 7-chloroindole, and 7-bromoindole, eradicated persister formation by E. coli and S. aureus, and 5-iodoindole most potently inhibited biofilm formation by the two bacteria. Unlike other antibiotics, 5-iodoindole did not induce persister cell formation, and 5-iodoindole inhibited the production of the immune-evasive carotenoid staphyloxanthin in S. aureus; hence, 5-iodoindole diminished the production of virulence factors in this strain. These results demonstrate halogenated indoles are potentially useful for controlling bacterial antibiotic resistance.
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U2 - 10.1186/s13568-016-0297-6
DO - 10.1186/s13568-016-0297-6
M3 - Article
AN - SCOPUS:85002487986
VL - 6
JO - AMB Express
JF - AMB Express
SN - 2191-0855
IS - 1
M1 - 123
ER -