Premium
Highly Active Modulators of Indole Signaling Alter Pathogenic Behaviors in Gram‐Negative and Gram‐Positive Bacteria
Author(s) -
Minvielle Marine J.,
Eguren Kristen,
Melander Christian
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201303510
Subject(s) - indole test , biofilm , tryptophanase , pathogenic bacteria , microbiology and biotechnology , gram negative bacteria , bacteria , regulator , biology , chemistry , biochemistry , escherichia coli , gene , genetics
Indole is a universal signal that regulates various bacterial behaviors, such as biofilm formation and antibiotic resistance. To generate mechanistic probes of indole signaling and control indole‐mediated pathogenic phenotypes in both Gram‐positive and Gram‐negative bacteria, we have investigated the use of desformylflustrabromine (dFBr) derivatives to generate highly active indole mimetics. We have developed non‐microbicidal dFBr derivatives that are 27–2000 times more active than indole in modulating biofilm formation, motility, acid resistance, and antibiotic resistance. The activity of these analogues parallels indole, because they are dependent on temperature, the enzyme tryptophanase TnaA, and the transcriptional regulator SdiA. This investigation demonstrates that molecules based on the dFBr scaffold can alter pathogenic behaviors by mimicking indole‐signaling pathways.