This proposal will characterize the efficacy of antibiotics on three different medically significant bacteria cultured under spaceflight analogue conditions. The three bacterial pathogens proposed for use in this study are: Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa, and Staphylococcus aureus. The specific role of my lab in the proposed work will be to examine the effect of spaceflight analogue culture conditions on the antibiotic resistance profile of S. Typhimurium. A basic overview of this project is provided below. The consequence of infectious disease during the human exploration of space is greatly dependent on the efficacy of the countermeasures used to minimize the impact of the infection. As antimicrobials are the primary post-infection countermeasure against infectious disease aboard spacecraft, understanding the pharmacodynamics of antibiotics during a mission is of critical importance to mitigate the health, safety and performance risk for the crew. This is especially important given the immunocompromised state of the crew during spaceflight and our discovery that spaceflight uniquely increased the virulence of the foodborne pathogen, Salmonella enterica serovar Typhimurium. While previous spaceflight experiments have indicated alterations in antibiotic resistance, the specific mechanisms behind these changes have not been elucidated. Limited information is available regarding the impact of the spaceflight environment on the efficacy of antibiotics due to the paucity of opportunities for spaceflight experiments, suggesting a need for ground-based analogues that provide (a) preliminary data indicative of spaceflight response prior to a true spaceflight experiment, and (b) a technique to follow up spaceflight findings without the delays associated with true spaceflight experiments. One proven spaceflight analogue, the NASA-designed Rotating Wall Vessel (RWV) bioreactor, creates a growth environment in which planktonic cells experience low fluid shear culture similar to that which they would encounter during spaceflight. We have shown the RWV provides data on microbial responses that are indicative or confirmatory of bacterial responses in spaceflight, including alterations in virulence and gene regulation. The molecular genetic evaluation of S. Typhimurium cultured in the RWV indicated alterations in the regulation of ABC transporter genes, which suggests a potential for antibiotic resistance. Likewise, alterations in biofilm characteristics were observed in both the RWV culture of P. aeruginosa and S. aureus, again suggesting the potential of antibiotic resistance. Expanding upon these findings, we hypothesize that bacteria cultured in the low shear RWV environment will demonstrate changes in antibiotic efficacy compared to higher shear controls. To address this hypothesis, we propose to determine the minimum inhibitory concentrations (MICs) of selected antibiotics currently manifested during NASA missions on three medically significant model bacterial pathogens that have either been isolated from spaceflight vehicles or have a clear route of infection for the crew. The three model pathogens proposed for use in this study are: Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa and Staphylococcus aureus. Antibiotic selection was based upon availability aboard the International Space Station (ISS) and typical clinical guidelines, with some consideration given to diversity of mechanism of antibiosis. Thus, the proposed study is a logical direct extension of our previous RWV and spaceflight investigations and a critical component in the mitigation of the impact of infectious disease risk to ensure the success of the long-duration human exploration of space.
|Effective start/end date||9/30/13 → 3/30/14|
- National Aeronautics Space Administration (NASA): $55,000.00