Frontiers in Cellular and Infection Microbiology (Aug 2012)
The Effect of Low Shear Force on the Virulence Potential of Yersinia pestis: New aspects that Space-Like Growth Conditions and the Final Frontier can teach us about a Formidable Pathogen
Abstract
Manned space exploration has created a need to evaluate the effects of space-like stress (SLS) on pathogenic and opportunistic microbes. Interestingly, several Gram-negative enteric pathogens, e.g., Salmonella enterica serovar Typhimurium, have revealed a transient hyper-virulent phenotype following simulated microgravity (SMG) or actual space flight exposures. We have explored the virulence potential of Yersinia pestis KIM/D27 (YP) following exposure to mechanical low shear forces associated with SMG in various bodily fluids of an infected host which could provide new insights into its pathogenesis. In our seminal studies, the effects of low shear force on YP KIM/D27 proliferation and the type three secretion system (T3SS) functions were evaluated. For most studies, a KIM/D27 ΔyopB mutant strain lacking the ability to inject Yersinia outer proteins (Yops) into the targeted host cell was used as an internal negative control. Our experimental results demonstrated that SMG-grown YP was decreased in its induced magnitude of host cell rounding when employing HeLa cells in a cytotoxicity assay than did the NG-grown bacteria, suggesting that SMG somehow compromises T3SS functions. This was confirmed by an actual reduced amount of effector protein production and secretion through the T3SS injectisome. Also, SMG-grown YP used to infect cultured RAW 246.7 macrophages proliferated less than their NG-grown counterparts during the 8-hour infection period. Presently, we are evaluating the influence of SMG on various KIM/D27 mutant strains to further understanding of our initial phenomenology described above. Taken together, characterizing YP grown under the low shear forces of SMG can provide new insights into its pathogenesis and potentially uncover new targets that could be exploited for the development of novel antimicrobials as well as potential live-attenuated vaccines.
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