Peeling the onion: additional layers of regulation in the acid stress response

Research output: Contribution to journalReview articlepeer-review


Bacteria are capable of withstanding large changes in osmolality and cytoplasmic pH, unlike eukaryotes that tightly regulate their pH and cellular composition. Previous studies on the bacterial acid stress response described a rapid, brief acidification,followed by immediate recovery. More recent experiments with better pH probes have imaged single living cells, and we now appreciate that following acid stress, bacteria maintain an acidic cytoplasm for as long as the stress remains. This acidificationenables pathogens to sense a host environment and turn on their virulence programs, for example, enabling survival and replication within acidic vacuoles. Single-cell analysis identifiedan intracellular pH threshold of ∼6.5. Acid stress reduces the internal pH below this threshold, triggering the assembly of a type III secretion system in Salmonella and the secretion of virulence factors in the host. These pathways are significantbecause preventing intracellular acidificationof Salmonella renders it avirulent, suggesting that acid stress pathways represent a potential therapeutic target. Although we refer to the acid stress response as singular, it is actually a complex response that involves numerous two-component signaling systems, several amino acid decarboxylation systems, as well as cellular bufferingsystems and electron transport chain components, among others. In a recent paper in the Journal of Bacteriology, M. G. Gorelik, H. Yakhnin, A. Pannuri, A. C. Walker, C. Pourciau, D. Czyz, T. Romeo, and P. Babitzke (J Bacteriol 206:e00354-23, 2024, describe a new connection linking the carbon storage regulator CsrA to the acid stress response, highlighting new additional layers of complexity.

Original languageEnglish (US)
JournalJournal of bacteriology
Issue number4
StatePublished - Apr 2024


  • CsrA
  • Salmonella pathogenicity island
  • SsrB
  • acid stress response
  • amino acid decarboxylation
  • carbon storage regulation
  • two-component regulatory systems

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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