Surviving the acid test: responses of gram-positive bacteria to low pH

Abstract

Gram-positive bacteria possess a myriad of acid resistance systems that can help them to overcome the challenge posed by different acidic environments. In this review the most common mechanisms are described: i.e., the use of proton pumps, the protection or repair of macromolecules, cell membrane changes, production of alkali, induction of pathways by transcriptional regulators, alteration of metabolism, and the role of cell density and cell signaling. We also discuss the responses of Listeria monocytogenes, Rhodococcus, Mycobacterium, Clostridium perfringens, Staphylococcus aureus, Bacillus cereus, oral streptococci, and lactic acid bacteria to acidic environments and outline ways in which this knowledge has been or may be used to either aid or prevent bacterial survival in low-pH environments.

FIG. 1.

Graphical presentation of the mechanisms of resistance available to gram-positive bacteria. These have been divided into eight categories, and a number of examples are demonstrated. (i) Proton pumps such as the F₁F₀ATPase or that utilized by the GAD system bring about an increase in internal pH. (ii) Proton repair involving chaperones, proteases, and heat shock proteins results in the protection of proteins or their degradation if damaged. (iii) DNA damaged as a consequence of a low internal pH can be repaired through the excision of errors or the restarting of stalled replication forks. (iv) The involvement of regulators such as 2CSs and sigma factors can induce minor or global responses. (v) Cell density affects cell-to-cell communication. (vi) Cell envelope alterations can protect cells by changing architecture, composition, stability, and activity. (vii) The production of alkali by the ADI or urease system increases the internal pH of the cell. (viii) Metabolic properties can be altered.

FIG. 2.

Acidic environments where the survival of bacteria has an impact on health or the economy. While contributory factors are listed, these do not include genes and acid resistance systems associated with individual bacteria.

FIG. 3.

(A) Alignment of ADI gene clusters. arcA, arginine deiminase; arcB, ornithine transcarbamylase; arcC, carbamate kinase; arcR, Crp/Fnr-type regulator; arcD, ornithine/arginine antiporter; arcT, noncharacterized transaminase; argR, arginine of the ArgR-AhrC family. The identities of a number of the genes indicated above remain putative (L. sakei [262, 263], E. faecalis [11], S. gordonii [78], S. pyogenes [74], S. suis [250], and O. oeni [228]). (B) Alignment of F₁F₀-ATPase operons (C) Alignment of of genes involved in regulation of sigB. (Panel B is based on data in reference ; Panel C is based on data in reference .)

FIG. 4.

Generation of ATP by transport and proton-consuming decarboxylation. The movement of glutamate (Glu²⁻) ions into the cell, glutamate decarboxylation, and extrusion of GABA ions (GABA⁻), the movement of malate (Mal²⁻) ions into the cell, malate decarboxylation, and extrusion of lactate (Lac⁻) ions (L. lactis), and the movement of citrate (HCit²⁻) ions into the cell, oxaloacetate decarboxylation, and extrusion of Lac ions (Lac⁻) (L. lactis) all create an electrogenic potential. These decarboxylation reactions and the consumption of a proton increase the alkalinity of the cytoplasm. Three cycles of decarboxylation and antiport create a PMF sufficient for the synthesis of ATP via the F₁F₀-ATPase. Ace⁻, acetate; Oxace²⁻, oxaloacetate; Pyr, pyruvate.