Acid survival mechanisms in neutralophilic bacteria

Numerous commensal and pathogenic Gram-negative and Gram-positive bacteria are referred to as neutralophiles because they grow best at pH levels close to neutrality. Thus, exposure to harsh-to-mild acidic environments, such as those encountered in the digestive tract of animal hosts, in the phagosome of macrophages, in fermented foods, but also in the soil or in acid mine drainage, is a rather common encounter for neutralophiles during their life cycle. As a result, it is not surprising that most of them have evolved sophisticated molecular mechanisms to cope with low pH. These protective mechanisms provide neutralophiles with the ability to sense acid pH and keep under control the intracellular acidification of the cytoplasm, thus avoiding protons from reaching such harmful levels as to compromise cellular vitality, which relies on the proper functioning of many biological macromolecules at pH levels near neutrality. The aim of this chapter is to provide an overview of the most commonly employed, and best characterized, molecular systems in a number of Gram-positive and Gram-negative bacteria. How they work inside the cell and how their activity can be linked to virulence are highlighted. The biochemistry and distribution of the glutamate-dependent acid resistance system among orally acquired bacteria are described in some detail.