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Front. Microbiol. | doi: 10.3389/fmicb.2018.00310

Spaceflight modifies Escherichia coli gene expression in response to antibiotic exposure and reveals role of oxidative stress response

Thomas R. Aunins1, Keesha E. Erickson1, Nripesh Prasad2, Shawn E. Levy2, Angela Jones2, Shristi Shrestha2, 3, Rick Mastracchio4, Mike Hopkins4,  Louis Stodieck5, David Klaus6,  Luis Zea5* and  Anushree Chatterjee1, 7*
  • 1Chemical and Biological Engineering, University of Colorado Boulder, United States
  • 2HudsonAlpha Institute for Biotechnology, United States
  • 3Biological Science, University of Alabama in Huntsville, United States
  • 4Johnson Space Center, National Aeronautics and Space Administration (NASA), United States
  • 5Aerospace Engineering Sciences, University of Colorado Boulder, United States
  • 6Aerospace Engineering Sciences, University of Colorado Boulder, United States
  • 7University of Colorado Boulder, United States

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 hours 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.

Keywords: Escherichia coli, spaceflight, RNA-sequencing, antibiotic, tolerance, Oxidative Stress, bioastronautics, microgravity

Received: 06 Dec 2017; Accepted: 09 Feb 2018.

Edited by:

MASAHIRO ITO, Toyo University, Japan

Reviewed by:

Blanca Barquera, Rensselaer Polytechnic Institute, United States
Aldo Nicosia, Istituto per l'Ambiente Marino Costiero (CNR), Italy  

Copyright: © 2018 Aunins, Erickson, Prasad, Levy, Jones, Shrestha, Mastracchio, Hopkins, Stodieck, Klaus, Zea and Chatterjee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Luis Zea, University of Colorado Boulder, Aerospace Engineering Sciences, 429 UCB, Boulder, 80309, Colorado, United States, Luis.Zea@colorado.edu
Prof. Anushree Chatterjee, University of Colorado Boulder, Chemical and Biological Engineering, JSC Biotech Bldg, 3415 Colorado Ave, D179, Boulder, 80303, Colorado, United States, chatterjee@colorado.edu