Understanding How Microorganisms Respond to Acid pH Is Central to Their Control and Successful Exploitation

Abstract

Microbes from the three domains of life, Bacteria, Archaea, and Eukarya, share the need to sense and respond to changes in the external and internal concentrations of protons. When the proton concentration is high, acidic conditions prevail and cells must respond appropriately to ensure that macromolecules and metabolic processes are sufficiently protected to sustain life. While, we have learned much in recent decades about the mechanisms that microbes use to cope with acid, including the unique challenges presented by organic acids, there is still much to be gained from developing a deeper understanding of the effects and responses to acid in microbes. In this perspective article, we survey the key molecular mechanisms known to be important for microbial survival during acid stress and discuss how this knowledge might be relevant to microbe-based applications and processes that are consequential for humans. We discuss the research approaches that have been taken to investigate the problem and highlight promising new avenues. We discuss the influence of acid on pathogens during the course of infections and highlight the potential of using organic acids in treatments for some types of infection. We explore the influence of acid stress on photosynthetic microbes, and on biotechnological and industrial processes, including those needed to produce organic acids. We highlight the importance of understanding acid stress in controlling spoilage and pathogenic microbes in the food chain. Finally, we invite colleagues with an interest in microbial responses to low pH to participate in the EU-funded COST Action network called EuroMicropH and contribute to a comprehensive database of literature on this topic that we are making publicly available.

Keywords: acid stress; food spoilage; industrial processes; intracellular pH homeostasis; microbial infections; organic acids; photosynthesis.

Figure 1

Summary of known mechanisms for responding to low pH stress in microbes. The schematic illustrates some of the better-studied mechanisms used by Gram negative (A) and Gram-positive bacteria (B) and yeasts (C) for responding to acidic conditions. Protonated weak organic acid permeation across the plasma membrane is illustrated in part (C) but this also applies in the inner membrane of bacterial cells. The details are discussed in the text where the relevant references are provided. OM, outer membrane; IM, inner membrane; PM: plasma membrane; Gln, glutamine; Glu, glutamate; GABA, γ-aminobutyric acid; Arg, arginine; Agm, agmatine; Lys, lysine; Cad, cadaverine; UFA, unsaturated fatty acids; CFA, cyclopropane fatty acids; RCOOH, organic acid in the undissociated form; RCOO^– , organic acid in the dissociated form (i.e., proton loss).

Figure 2

Approaches to understanding the responses of microbes to low pH at different organizational levels. The graphic highlights the research approaches (blue boxes) that can be used to study acid pH responses at each organizational level, from genomes through to ecosystems (represented by the images on the left). The presence of specific genes in the genome and their regulation in response to acid determines the cells’ capacity to cope with low pH stress (I). Acid-induced proteins are responsible for structural and metabolic changes in the cell, resulting in altered molecular composition at low pH (II). At the cellular level, acidic pH can have strong effect on the overall growth and behavior of the microbes (III), but with a population of cells there can be genetic and biochemical heterogeneity leading to different behavioral outcomes (IV). Within mixed communities both the population structure and inter-species and intra-species interactions can be strongly influenced by changes in pH (V).