title: Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli.
abstract: Persisters are cells which evade stresses like antibiotics and which are characterized by reduced metabolism and a lack of genetic alterations required to achieve this state. We showed previously that MqsR and MqsA of Escherichia coli are a toxin-antitoxin pair that influence cell physiology (e.g., biofilm formation and motility) via RNase activity as well as through regulation of toxin CspD. Here, we show that deletion of the mqsRA locus decreases persister cell formation and, consistent with this result, over production of MqsR increases persister cell formation. Furthermore, toxins Hha, CspD, and HokA increase persister cell formation. In addition, by overproducing MqsR in a series of isogenic mutants, we show that Hha and CspD are necessary for persister cell formation via MqsR overexpression. Surprisingly, Hfq, a small RNA chaperone, decreases persistence. A whole-transcriptome study shows that Hfq induces transport-related genes (opp genes and dppA), outer membrane protein-related genes (ybfM and ybfN), toxins (hha), and proteases (clpX, clpP, and lon). Taken together, these results indicate that toxins CspD, Hha, and HokA influence persister cell formation via MqsR and that Hfq plays an important role in the regulation of persister cell formation via regulation of transport or outer membrane proteins OppA and YbfM.
authors.affiliation: Department of Chemical Engineering, Texas A and M University, College Station, TX 77843-3122, United States.
authors.forename: Younghoon
authors.initials: Y
authors.lastname: Kim
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D035001:Host Factor 1 Protein / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; C087373:Hfq protein, E coli; C087025:Hok protein, E coli; D035001:Host Factor 1 Protein; C508571:MqsR protein, E coli; C490240:cspH protein, E coli; C079209:hha protein, E coli; D012313:RNA