Spaceflight Modifies Escherichia coli Gene Expression in Response to Antibiotic Exposure and Reveals Role of Oxidative Stress Response

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.

Increased growth rate and amikacin resistance of Salmonella enteritidis after one‐month spaceflight on China’s Shenzhou‐11 spacecraft

“…Spaceflight could affect the drug resistance phenotype of bacteria and a profound drug resistance capacity of ISS microorganisms against environmental stresses was detected during these years (Mora et al, ; Singh et al, ; Urbaniak et al, ). It has been demonstrated that the increased antibiotic tolerance of Escherichia coli in human spaceflight environment might be attributed to the upregulation of genes related to oxidative stress response (Aunins et al, ). Another study from China also pointed out that spaceflight changed the antibiotic susceptibility of Klebsiella pneumonia and resulted in bacterial resistance to sulfamethoxazole, the mechanism was that the spaceflight strain of K. pneumonia contained an additional copy of the sul1 gene, which encoded a substituted form of dihydrofolate synthetase and could not be inhibited by the drug (Guo et al, ).…”

Antimicrobial Photoinactivation Approach Based on Natural Agents for Control of Bacteria Biofilms in Spacecraft

“…In two days, E. coli grown in space, compared with the Earth control, adapted to higher gentamicin concentrations. Moreover, the strain on the ISS showed upregulation of 50 stress response genes, suggesting that microgravity induces stress responses associated with antibiotic stress and likely increases antibiotic tolerance in bacteria in space [3,11,52]. Indeed, in bacteria isolated from the ISS, increased resistance to antibiotics has often been reported.…”

Design of a spaceflight biofilm experiment

“…Separately, we observed an enhancement of planktonic cell aggregation during the Antibiotic Effectiveness in Space (AES-1) experiment conducted on board ISS [ 15 , 16 ] (similar to the observations reported in Wilson et al [ 17 ]), which occurred in parallel to differential gene expression indicating cells in space were under higher levels of stress than matched Earth controls [ 18 ]. More recently, we also reported an activation of drug-resistance mechanisms in space as a result of these microgravity-derived stresses [ 19 ].…”