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Bacteria cope with life in harsh environments using specific stress responses and chemical alterations of cell components. Biochemical strategies for survival at low pH are explored using a naturally acid-resistant bacterium. Acid tolerance is an area underexplored by biochemists, despite its importance for the survival of numerous human pathogens, including E. coli O157, M. tuberculosis, and Salmonella. Most studies focus on the induction of acid resistance in organisms that prefer to grow at near-neutral pH. Carboxylic acids are especially toxic to bacteria at low pH because they easily cross hydrophobic lipid membranes as acid pairs:
A bacterium that produces immense amounts of toxic acetic acid, A. aceti, has the ability to handle low pH in general -- its cytoplasmic pH can drop as low as 4 -- and acetic acid in particular. This Gram-negative, plant-associated bacterium has been used for millenia in the production of vinegar.
The structures and kinetic mechanisms of ordinarily acid-sensitive enzymes adapted to these conditions will be explored. We have already cloned a few and are in the process of studying them. Components of a specific acetic acid response system in A. aceti, including a potential response regulator, will be studied using biophysical techniques. Current Funding Herman Frasch Foundation for Research in Agricultural Chemistry, 07/01/02 06/30/07 National Science
Foundation CAREER Award, 06/01/04-05/31/09. |