A Role for the SmpB-SsrA System in Yersinia pseudotuberculosis Pathogenesis

Open Access
Publisher Website
Google Scholar
Abstract
Yersinia utilizes a sophisticated type III secretion system to enhance its chances of survival and to overcome the host immune system. SmpB (small protein B) and SsrA (small stable RNA A) are components of a unique bacterial translational control system that help maintain the bacterial translational machinery in a fully operational state. We have found that loss of the SmpB-SsrA function causes acute defects in the ability of Yersinia pseudotuberculosis to survive in hostile environments. Most significantly, we show that mutations in smpB-ssrA genes render the bacterium avirulent and unable to cause mortality in mice. Consistent with these observations, we show that the mutant strain is unable to proliferate in macrophages and exhibits delayed Yop-mediated host cell cytotoxicity. Correspondingly, we demonstrate that the smpB-ssrA mutant suffers severe deficiencies in expression and secretion of Yersinia virulence effector proteins, and that this defect is at the level of transcription. Of further interest is the finding that the SmpB-SsrA system might play a similar role in the related type III secretion system that governs flagella assembly and bacterial motility. These findings highlight the significance of the SmpB-SsrA system in bacterial pathogenesis, survival under adverse environmental conditions, and motility. Bacteria have evolved sophisticated mechanisms to monitor, adapt, and respond to environmental and host-mediated assaults. Many Gram-negative pathogenic bacteria utilize a needle-like type III secretion system (TTSS) to inject a cocktail of effector proteins into host cells, disabling the host defenses against the pathogen. There is evolutionary, structural, and sequence similarity between this TTSS and the bacterial motility apparatus, the flagellum. Experiments described in this study examine the role played by the SmpB-SsrA system in Yersinia virulence, motility, and adaptation to adverse environments. The authors present evidence to demonstrate that an smpB-ssrA mutant of Yersinia pseudotuberculosis is more sensitive to adverse environmental conditions, lacks motility, exhibits severe defects in Yop secretion, and is avirulent in a mouse infection model. On the basis of these findings, they postulate that the SmpB-SsrA system, through its ribosome rescue, and protein tagging for directed degradation functions, affects the expression of the Ysc-Yop TTSS, and likely the flagellar TTSS, at the level of transcription. Their findings are consistent with a proposed regulatory role for the SmpB-SsrA system in regulation of bacterial gene expression.