Attaching and effacing pathogens modulate host mitochondrial structure and function

Anusha Harishankar, V. K. Viswanathan

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are human enteric pathogens that contribute significantly to morbidity and mortality worldwide. These extracellular pathogens attach intimately to intestinal epithelial cells and cause signature lesions by effacing the brush border microvilli, a property they share with other “attaching and effacing” (A/E) bacteria, including the murine pathogen Citrobacter rodentium. A/E pathogens use a specialized apparatus called a type III secretion system (T3SS) to deliver specific proteins directly into the host cytosol and modify host cell behavior. The T3SS is essential for colonization and pathogenesis, and mutants lacking this apparatus fail to cause disease. Thus, deciphering effector-induced host cell modifications is critical for understanding A/E bacterial pathogenesis. Several of the ∼20–45 effector proteins delivered into the host cell modify disparate mitochondrial properties, some via direct interactions with the mitochondria and/or mitochondrial proteins. In vitro studies have uncovered the mechanistic basis for the actions of some of these effectors, including their mitochondrial targeting, interaction partners, and consequent impacts on mitochondrial morphology, oxidative phosphorylation and ROS production, disruption of membrane potential, and intrinsic apoptosis. In vivo studies, mostly relying on the C. rodentium/mouse model, have been used to validate a subset of the in vitro observations; additionally, animal studies reveal broad changes to intestinal physiology that are likely accompanied by mitochondrial alterations, but the mechanistic underpinnings remain undefined. This chapter provides an overview of A/E pathogen-induced host alterations and pathogenesis, specifically focusing on mitochondria-targeted effects.

Original languageEnglish (US)
Title of host publicationMitochondria and Bacterial Pathogens - Part B
EditorsSaverio Marchi, Lorenzo Galluzzi
PublisherElsevier Inc.
Pages65-86
Number of pages22
ISBN (Print)9780443191237
DOIs
StatePublished - Jan 2023

Publication series

NameInternational Review of Cell and Molecular Biology
Volume377
ISSN (Print)1937-6448

Keywords

  • Attaching-effacing (A/E) pathogens
  • Cell death
  • Citrobacter rodentium
  • EPEC
  • Intestinal epithelium
  • Mitochondrial membrane potential
  • Mitochondrial morphology
  • Oxidative phosphorylation
  • Type 3 secretion system

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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