Abstract
Bacteria grown in space experiments under microgravity conditions have been found to undergo unique physiological responses, ranging from modified cell morphology and growth dynamics to a putative increased tolerance to antibiotics. A common theory for this behavior is the loss of gravity-driven convection processes in the orbital environment, resulting in both reduction of extracellular nutrient availability and the accumulation of bacterial byproducts near the cell. To further characterize the responses, this study investigated the transcriptomic response of Escherichia coli to both microgravity and antibiotic concentration. E. coli was grown aboard International Space Station in the presence of increasing concentrations of the antibiotic gentamicin with identical ground controls conducted on Earth. Here we show that within 49 h of being cultured, E. coli adapted to grow at higher antibiotic concentrations in space compared to Earth, and demonstrated consistent changes in expression of 63 genes in response to an increase in drug concentration in both environments, including specific responses related to oxidative stress and starvation response. Additionally, we find 50 stress-response genes upregulated in response to the microgravity when compared directly to the equivalent concentration in the ground control. We conclude that the increased antibiotic tolerance in microgravity may be attributed not only to diminished transport processes, but also to a resultant antibiotic cross-resistance response conferred by an overlapping effect of stress response genes. Our data suggest that direct stresses of nutrient starvation and acid-shock conveyed by the microgravity environment can incidentally upregulate stress response pathways related to antibiotic stress and in doing so contribute to the increased antibiotic stress tolerance observed for bacteria in space experiments. These results provide insights into the ability of bacteria to adapt under extreme stress conditions and potential strategies to prevent antimicrobial-resistance in space and on Earth.
Highlights
Among the many risks astronauts will face as they venture into missions beyond lower Earth orbit are those that arise from microbial responses to spaceflight
E. coli Response to Increasing Gentamicin Concentration. In these experiments it was found that E. coli cultures grown in the presence of gentamicin in microgravity were able to survive at higher concentrations of the drug than in a 1g gravitational regime on Earth (Figure 1C)
The gene thiH is one of these 50 stress response genes. This is consistent with the thi operon being related to nutrient starvation (Zea et al, 2016) and the trp operon being associated with indole metabolism, a molecule that is associated with antibiotic resistance in E. coli (Dunn et al, 1990; Yee et al, 1996; Hirakawa et al, 2005; Lee and Lee, 2010; Han et al, 2011; Vega et al, 2012)
Summary
Among the many risks astronauts will face as they venture into missions beyond lower Earth orbit are those that arise from microbial responses to spaceflight. Spaceflight has been shown to promote biofilm formation in bacteria, which may pose challenges involving biofouling, corrosion, the contamination of water sources, and increased bacterial virulence (McLean et al, 2001; Kim et al, 2013; Ott et al, 2016). Changes of microbial behavior observed in space include improved growth (Zea et al, 2017), decreased susceptibility to antibiotics (Tixador et al, 1985; Lapchine et al, 1986; Moatti et al, 1986; Tixador et al, 1994; Klaus and Howard, 2006; Kitts et al, 2007; Parra et al, 2008; Ricco et al, 2010), enhanced capability to form biofilms (McLean et al, 2001; Kim et al, 2013), formation of outer membrane vesicles (Zea et al, 2017), and increased virulence (Wilson et al, 2007, 2008), to name a few. At a time when understanding bacterial resistance mechanisms is increasingly important on Earth as multi-drug resistant strains have become increasingly common, experiments in microgravity offer another avenue through which antibiotic effectiveness may be explored (Erickson et al, 2015; Otoupal et al, 2017)
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