Evaluation of pathogenesis and biofilm formation ability of Yersinia pestis after 40-day exposure to simulated microgravity

Abstract

AbstractWith the increase of crewed space missions and the rise of space microbiology, the research of microbes grown under microgravity environment has been attracting more attention. The research scope in space microbiology has been extended beyond pathogens directly related to spaceflight. Y. pestis, the causative agent of plague, is also of interest to researchers. After being cultivated for 40 consecutive passages in either simulated microgravity (SMG) or normal gravity (NG) conditions, the Y. pestis strain 201 cultures were analysed regarding their phenotypic features. By using crystal violet staining assays, increased biofilm amount was detected in Y. pestis grown under SMG condition. Besides that, the damage degrees of Hela cell caused by SMG-grown Y. pestis were found diminished in comparison to those under NG condition. Consistent with this observation, the death course was delayed in mice infected with SMG-grown Y. pestis, suggesting that microgravity condition can contribute the attenuated virulence. RNA-seq-based transcriptomics analysis showed that a total of 218 genes were differentially regulated, of which 91 upregulated and 127 downregulated. We found that dozens of virulence-associated genes were downregulated, which partially explained the reduced virulence of Y. pestis under SMG condition. Our study demonstrated that long-term exposure to SMG influences the pathogenesis and biofilm formation ability of Y. pestis, which provides a novel avenue to study the mechanism of physiology and virulence of this pathogen. Microgravity enhanced the ability of biofilm formation and reduced the virulence and cytotoxicity of Y. pestis. Many virulence-associated genes of Y. pestis were differentially regulated in response to the stimulated microgravity. However, there is no molecular evidence to explain the enhanced biofilm formation ability, which requires further research. Taken together, the phenotype changes of Y. pestis under SMG conditions can provide us a new research direction of its potential pathogenesis.