Toxin YafQ increases persister cell formation by reducing indole signalling

• Published in: Environmental microbiology 2015-04, Vol.17 (4), p.1275-1285
• Main Authors: Hu, Ying, Kwan, Brian W., Osbourne, Devon O., Benedik, Michael J., Wood, Thomas K.
• Format: Article
• Language: English
• Subjects: Antitoxins - genetics; Bacterial Proteins - metabolism; Bacterial Toxins - genetics; Bacterial Toxins - metabolism; Escherichia coli; Escherichia coli - genetics; Escherichia coli - pathogenicity; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Indoles - analysis; Manufacturing cells; Metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sigma Factor - metabolism; Signal Transduction; Tryptophan - chemistry; Tryptophanase - biosynthesis; Tryptophanase - genetics; Tryptophanase - metabolism
• ISSN: 1462-2912; 1462-2920
• DOI: 10.1111/1462-2920.12567

Summary Persister cells survive antibiotic and other environmental stresses by slowing metabolism. Since toxins of toxin/antitoxin (TA) systems have been postulated to be responsible for persister cell formation, we investigated the influence of toxin YafQ of the YafQ/DinJ Escherichia coli TA system on persister cell formation. Under stress, YafQ alters metabolism by cleaving transcripts with in‐frame 5′‐AAA‐G/A‐3′ sites. Production of YafQ increased persister cell formation with multiple antibiotics, and by investigating changes in protein expression, we found that YafQ reduced tryptophanase levels (TnaA mRNA has 16 putative YafQ cleavage sites). Consistently, TnaA mRNA levels were also reduced by YafQ. Tryptophanase is activated in the stationary phase by the stationary‐phase sigma factor RpoS, which was also reduced dramatically upon production of YafQ. Tryptophanase converts tryptophan into indole, and as expected, indole levels were reduced by the production of YafQ. Corroborating the effect of YafQ on persistence, addition of indole reduced persistence. Furthermore, persistence increased upon deleting tnaA, and persistence decreased upon adding tryptophan to the medium to increase indole levels. Also, YafQ production had a much smaller effect on persistence in a strain unable to produce indole. Therefore, YafQ increases persistence by reducing indole, and TA systems are related to cell signalling.