|Andreozzi, Eliza - Collaborator|
|Zhanf, Xinmin - Collaborator|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2018
Publication Date: 5/2/2018
Citation: Uhlich, G.A., Andreozzi, E., Cottrell, B.J., Reichenberger, E.R., Zhanf, X., Paoli, G. 2018. Sulfamethoxazole – Trimethoprim represses csgD but maintains virulence genes at 30 deg C in a clinical Escherichia coli O157:H7 isolate. PLoS One. https://doi.org/10.1371/journal.pone.0196271.
Interpretive Summary: Escherichia coli serotype O157:H7 is the causative agent of hemorrhagic diarrhea associated with the ingestion of contaminated meats and produce. Many O157:H7 strains carry multiple viruses integrated at various locations within their genomes. These inserted viruses can disrupt E. coli genes or affect gene expression. Treatment of serotype O157:H7-infected patients with antibiotics, such as Sulfamethoxizole-Trimethoprim (SMX-TM), can activate the inserted viruses and further alter the ability of the O157:H7 bacterium to cause disease and form stress-protective biofilms. We tested the effects of different concentrations of SMX-TM on a clinical strain of serotype O157:H7 and determined that certain concentrations drastically increased the expression of disease-causing genes while decreasing the expression of protective biofilm genes. The results of this study will help clinicians to determine the correct antibiotics and dosages for treating patients and will aid researchers in developing strategies for inactivating serotype O157:H7 in foods.
Technical 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 can restore certain mlrA properties. In this study we used transcriptomics to study the affect of high and low sulfamethoxizole–trimethoprim (SMX-TM) concentrations on prophage induction, biofilm regulation, and virulence gene expression in strain PA20 under environmental conditions following five-hour and 12-hour exposures. 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 suppression. 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 suppressed at five hours, in spite of early SOS initiation by the higher SMX-TM concentration. Our findings indicate that during a switch from host to more environmental conditions, induction of PA20 HTR by SOS activation sustains strong virulence gene expression and enhances rather than relieves csgD repression.