Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria

The ability of enteropathogens such as Salmonella and Escherichia coli to adapt and survive acid stress is fundamental to their pathogenesis. Once inside the host, these organisms encounter life-threatening levels of inorganic acid (H+) in the stomach and a combination of inorganic and organic acids (volatile fatty acids) in the small intestine. To combat these stresses, enteric bacteria have evolved elegant, overlapping strategies that involve both constitutive and inducible defense systems. This article reviews the recent progress made in understanding the pH 3 acid tolerance systems of Salmonella and the even more effective pH 2 acid resistance systems of E. coli. Focus is placed on how Salmonella orchestrates acid tolerance by modulating the activities or levels of diverse regulatory proteins in response to pH stress. The result is induction of overlapping arrays of acid shock proteins that protect the cell against acid and other environmental stresses. Most notable among these pH-response regulators are RpoS, Fur, PhoP and OmpR. In addition, we will review three dedicated acid resistance systems of E. coli, not present in Salmonella, that allow this organism to survive extreme (pH 2) acid challenge.