Sulfamethoxazole - Trimethoprim represses csgD but maintains virulence genes at 30°C in a clinical Escherichia coli O157:H7 isolate

PLoS One. 2018 May 2;13(5):e0196271. doi: 10.1371/journal.pone.0196271. eCollection 2018.

Abstract

The high frequency of prophage insertions in the mlrA gene of clinical serotype O157:H7 isolates renders such strains deficient in csgD-dependent biofilm formation but prophage induction may restore certain mlrA properties. In this study we used transcriptomics to study the effect of high and low sulfamethoxazole-trimethoprim (SMX-TM) concentrations on prophage induction, biofilm regulation, and virulence gene expression in strain PA20 under environmental conditions following 5-hour and 12-hour exposures in broth or on agar. SMX-TM at a sub-lethal concentration induced strong RecA expression resulting in concentration- and time-dependent major transcriptional shifts with emphasis on up-regulation of genes within horizontally-transferred chromosomal regions (HTR). Neither high or low levels of SMX-TM stimulated csgD expression at either time point, but both levels resulted in slight repression. Full expression of Ler-dependent genes paralleled expression of group 1 pch homologues in the presence of high glrA. Finally, stx2 expression, which is strongly dependent on prophage induction, was enhanced at 12 hours but repressed at five hours, in spite of early SOS initiation by the high SMX-TM concentration. Our findings indicate that, similar to host conditions, exposure to environmental conditions increased the expression of virulence genes in a clinical isolate but genes involved in the protective biofilm response were repressed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • DNA, Bacterial / genetics
  • Escherichia coli O157 / genetics
  • Escherichia coli O157 / isolation & purification
  • Escherichia coli O157 / pathogenicity*
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / genetics
  • Gene Expression Regulation, Bacterial / drug effects*
  • Humans
  • Prophages / genetics
  • Rec A Recombinases / biosynthesis
  • Receptors, Glycine / genetics
  • Shiga Toxin 2 / biosynthesis*
  • Shiga Toxin 2 / genetics
  • Trans-Activators / antagonists & inhibitors*
  • Transcription, Genetic / drug effects
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Virulence / genetics
  • Virus Activation / drug effects

Substances

  • Anti-Bacterial Agents
  • CsgD protein, E coli
  • DNA, Bacterial
  • Escherichia coli Proteins
  • MlrA protein, E coli
  • Receptors, Glycine
  • Shiga Toxin 2
  • Trans-Activators
  • shiga toxin 2 B subunit
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Rec A Recombinases

Grants and funding

This work was supported by United States Department of Agriculture, Agricultural Research Service, National Program 108 Food Safety [Project # 8072-42000-076] (GAU). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Neither Dr. Xinmin Zhang or BioInfoRx Inc. provided financial support in any form. The specific roles of this author are detailed in the ‘Author Contributions’ section. Dr. Xinmin Zhang’s affiliation with BioInfoRx, Inc.