Scientists from the research groups of Prof. Dr. Susana Andrade and Prof. Dr. Oliver Einsle, members of the Institute of Organic Chemistry and the Cluster of Excellence BIOSS, the Centre for Biological Signalling Studies of the University of Freiburg, have collected the first precise data ever on the function of a transport protein for formate -- an important metabolite in bacteria.
The findings could potentially lead to the development of new antibiotic active ingredients, as the research team reports in the scientific journal PNAS.
The microbial intestinal flora of mammals is composed of various microorganisms and species of bacteria. The human intestine is home to several hundred grams of microorganisms, which are particularly essential in processing food. In an environment that is rich in nutrients and carbohydrates but poor in oxygen, many species of bacteria have developed a special form of metabolism: mixed-acid fermentation. The process involves breaking down sugar that enters into the intestine in foods to organic acids like formic acid, acetic acid, and lactic acid and then excreting them.
This provides the bacteria with energy but also leads to a considerable acidification of their environment, benefiting both good intestinal bacteria and pathogenic, i.e. disease causing, species like cholera bacteria and salmonella. Mixed-acid fermentation is missing in the human body. The molecular components of this process in bacteria thus provide a basis for developing new antibiotic active ingredients against the pathogenic species.
Formate is a central protein component in mixed-acid fermentation. Intestinal bacteria possess the formate channel FocA, a special transport protein that transports formate, the negatively charged ion of formic acid, over the cell membrane of the bacteria. In order to learn more about the function of FocA, Andrade introduced this protein into an artificial biological membrane and measured the electric currents of ions as they flowed through the formate channel. In addition to precise data on the transport behavior of FocA, the team succeeded in collecting detailed information on the channel's gating device: When the pH value of the environment is too low, it prevents bacteria from damaging themselves by continuing to export acids.
The Freiburg scientists also discovered that FocA can transport even more different anions: the ions of acetic acid, lactic acid, and pyruvic acid -- precisely the products of mixed-acid fermentation. The behavior of the channel for the various bonds corresponds to the proportions to which they are formed during the metabolism of sugar. The channel FocA thus has a much more central significance for this process than previously assumed. This could make it into an ideal basis for future therapeutic measures for diseases of the human intestinal tract.
- W. Lu, J. Du, N. J. Schwarzer, E. Gerbig-Smentek, O. Einsle, S. L. A. Andrade. The formate channel FocA exports the products of mixed-acid fermentation. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1204201109
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