1887

Abstract

In order to cause disease, pathogenic strains of rely on intricate regulatory networks to orchestrate the transition between their native aquatic environment and the human host. For example, bacteria in a nutrient-starved environment undergo a metabolic shift called the stringent response, which is mediated by the alarmone ppGpp and an RNA-polymerase binding transcriptional factor, DksA. In O1 serogroup strains of which use the toxin co-regulated pilus (TCP) and cholera toxin (CT) as primary virulence factors, DksA was reported to have additional functions as a mediator of virulence gene expression. However, little is known about the regulatory networks coordinating virulence phenotypes in pathogenic strains that use TCP/CT-independent virulence mechanisms. We therefore investigated whether functions of DksA outside of the stringent response are conserved in type three secretion system (T3SS)-positive . In using the T3SS-positive clinically isolated O39 serogroup strain AM-19226, we observed an increase in expression in the presence of bile at 37 °C. However, DksA was not required for wild-type levels of T3SS structural gene expression, or for colonization . Rather, data indicate that DksA positively regulates the expression of master regulators in the motility hierarchy. Interestingly, the Δ strain forms a less robust biofilm than the WT parent strain at both 30 and 37 °C. We also found that DksA regulates the expression of , encoding a major regulator of biofilm formation and protease expression. Athough DksA does not appear to modulate T3SS virulence factor expression, its activity is integrated into existing regulatory networks governing virulence-related phenotypes. Strain variations therefore may take advantage of conserved ancestral proteins to expand regulons responding to signals and thus coordinate multiple phenotypes important for infection.

Funding
This study was supported by the:
  • MadelineK. Sofia , National Institute of Allergy and Infectious Diseases , (Award AI118689)
  • MichelleDziejman , National Institute of Allergy and Infectious Diseases , (Award AI126005)
  • MichelleDziejman , National Institute of Allergy and Infectious Diseases , (Award R01AI073785)
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/content/journal/micro/10.1099/mic.0.001006
2020-12-17
2021-03-02
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