While unique responses in microorganisms are well documented for short duration culture, the impact of long duration, multigenerational growth of microorganisms in the chronic stress of microgravity has not been investigated. The implications of this gap in knowledge are tremendous, as the response to short duration growth in microgravity alters gene expression, pathogenesis-related stress responses (ex, biofilm formation and resistance to antibiotics) and virulence. Moreover, it is known that stress responses (including chronic stress) can increase mutagenesis in bacteria leading to genomic plasticity, which may provide novel mechanistic insight into genomic instability underlying resistance to antibiotics, pathogenicity, and virulence. We propose that long-term growth in spaceflight culture will induce heritable genomic and epigenetic changes in microorganisms with adverse phenotypic outcomes that could have a profound impact on the risk to crew health and vehicle system performance.
Our previous studies aboard the Space Shuttle investigated the response of the model enteric pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium) to short duration spaceflight culture and demonstrated a significant increase in virulence in a murine model of infection, in addition to biofilm formation, as compared to identically grown cultures on the ground. In addition, global microarray and proteomic analyses revealed that 167 transcripts (including small noncoding RNAs/ncRNAs) and 73 proteins changed expression, with the evolutionarily conserved protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq binds to small ncRNAs thereby facilitating their association with mRNAs, the outcome of which plays a diverse role in regulating gene expression, virulence, stress responses, antibiotic resistance, DNA methylation and genome stability.
We hypothesize that long-term multigenerational culture of S. Typhimurium in the spaceflight environment will result in stress-induced mutations and genomic instability as reflected in changes in the genomic, epigenetic, transcriptomic, and select phenotypic characteristics (including virulence) that will reflect a central role for Hfq as a global regulator of these heritable responses.
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To address the hypothesis, this study will characterize the impact of long term spaceflight culture (~300 generations) of an S. Typhimurium wild type and hfq mutant on the genomic, epigenetic, transcriptomic, virulence, and pathogenesis-related characteristics of these strains.
This experiment is currently in progress. Results will be available at the conclusion of the study.
Barrila J, Crabbé A, Yang J, Franco K, Nydam SD, Forsyth RJ, Davis RR, Gangaraju S, Ott CM, Coyne CB, Bissell MJ, Nickerson CA. Modeling host-pathogen interactions in the context of the microenvironment: 3-D cell culture comes of age. Infect Immun. 2018 Sep 4. [DOI]
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