Salmonella acid shock proteins are required for the adaptive acid tolerance response

Abstract

Salmonella typhimurium, as well as other enteric bacteria, experiences significant fluctuations in H+ ion concentrations during growth in diverse ecological niches. In fact, some pH conditions which should kill cells rapidly, such as stomach acidity, are nevertheless tolerated. The complete mechanism for this tolerance is unknown. However, I have recently demonstrated that S. typhimurium has the ability to survive extreme low pH (pH 3.0 to 4.0) if first adapted to mild pH (pH 5.5 to 6.0). This phenomenon has been referred to as the acidification tolerance response (ATR). The exposure to mild acid is referred to as preshock, and the proteins involved are called preshock ATR proteins. A second type of encounter with acid, called acid shock, involves shifting cells directly from alkaline conditions (pH 7.7) to acid conditions (pH 4.5 or below). During acid shock, the organism immediately ceases reproduction and dramatically changes the expression of at least 52 proteins. All but four are distinct from the preshock ATR proteins. Surprisingly, acid shock alone did not afford significant protection against strong acid challenge in minimal medium. Furthermore, inhibiting protein synthesis prior to acid shock revealed that the acid shock proteins do not appear to contribute to acid survival in minimal medium even at pH 4.3. Constitutive cellular pH homeostatic mechanisms seem sufficient to protect cells at this pH. The data suggest that the induction of acid shock and preshock ATR proteins are separate processes requiring separate signals. However, for S. typhimurium to survive extreme acid conditions, it must induce both the preshock and acid shock systems. Preventing the expression of one or the other eliminates acid tolerance. I propose a two-stage process that allows S. typhimurium to phase in acid tolerance as the environmental pH becomes progressively more acidic.