Antibiotic Fermentation Processes and Drug Development

BioServe, in collaboration with Bristol-Myers Squibb, is examining the effects of space flight on antibiotic fermentation processes. Initial microgravity experiments demonstrated relative increases in antibiotic production of between 75%-200% over ground-based controls. However, the absolute production level obtained in the early flight hardware used for these initial experiments was significantly less than that produced using a shaker flask in a typical laboratory setting. Recently, BioServe engineers designed and built a space flight qualified, fed-batch bioreactor that achieved production rates equivalent to shaker flasks (but without agitation) during 1g tests. This new device, termed MOBIAS, was most recently flown aboard ISS 8A in April 2002. Click here for a summary of that experiment. Data analysis is ongoing. Application of this knowledge is targeted at devising ways to improve the efficiency of the fermentation process here on Earth. A more efficient fermentation process, even by a small percentage, could potentially save millions of dollars in production costs. Contact Dr. David Klaus for additional information.

Tissue Engineering and Cell Culture

Space flight offers a unique opportunity in the areas of tissue engineering and cell culture. While some proteins and compounds can be produced in genetically engineered, simple organisms, such as E. coli or yeast, many proteins require post-translation modification that can only be achieved in mammalian cells or tissues. In most cases, such production relies on maintaining cells in a fully mature, differentiated state. Often cells that are grown in vitro will de-differentiate and lose their ability to produce and modify relevant proteins. However, recently tissues grown in microgravity or environments that simulate certain aspects of microgravity have been shown to retain or develop differentiated cell functions. The physical basis for this effect is thought to be due to the low-shear fluid environment that the cells and tissues encounter in real or simulated microgravity. By eliminating sedimentation, buoyancy and density driven convection, cells can be grown in a relatively quiescent fluid environment where interactions between cells can occur with minimal disruption. This allows cell aggregates and tissues to form not unlike tissue growth in vivo. Thus microgravity may be an ideal environment to conduct tissue-engineering research. BioServe is currently working with scientists from the Louisiana Veterans Research and Education Corporation on this project. Contact Dr. Louis Stodieck for additional information.

Antibiotic Effectiveness in Microgravity (controlling the spread of drug resistant pathogens)

Space flight has been shown to induce a number of changes in bacterial growth kinetics, such as increased final cell concentration and reduced lag phase duration. In addition, there is a reported ability to proliferate in the presence of normally inhibitory levels of various antibiotics. It is not yet clear, however, whether this net result is a function of an increase in the cell’s ability to resist the effects of the drug or a decrease in the effectiveness of the antibiotic due to a reduction in uptake rate. It is proposed that establishing a correlation between gravity-dependent mass transport phenomena and antibiotic efficacy can be used to help identify possible causal mechanisms associated with microbial drug resistance. This project is aimed at developing a novel research venue that can be used to better understand the microbial drug resistance acquisition process and to develop more effective countermeasures in preventing the spread of multi-drug resistant pathogens, both terrestrially and in the closed environment of a spacecraft. A commercial sponsor is currently being sought to develop this concept, especially as it relates to mitigating the spread of multi-drug resistant pathogens on Earth. Contact Dr. David Klaus for additional information.

BioServe Space Technologies – 429 UCB – Boulder, CO 80309 - Tel.+1(303) 492-1005 - Fax.+1(303) 492-8883