TY - CHAP
T1 - Attaching and effacing pathogens modulate host mitochondrial structure and function
AU - Harishankar, Anusha
AU - Viswanathan, V. K.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Attaching-effacing (A/E) pathogens
KW - Cell death
KW - Citrobacter rodentium
KW - EPEC
KW - Intestinal epithelium
KW - Mitochondrial membrane potential
KW - Mitochondrial morphology
KW - Oxidative phosphorylation
KW - Type 3 secretion system
UR - http://www.scopus.com/inward/record.url?scp=85151567112&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151567112&partnerID=8YFLogxK
U2 - 10.1016/bs.ircmb.2023.03.001
DO - 10.1016/bs.ircmb.2023.03.001
M3 - Chapter
C2 - 37268351
AN - SCOPUS:85151567112
SN - 9780443191237
T3 - International Review of Cell and Molecular Biology
SP - 65
EP - 86
BT - Mitochondria and Bacterial Pathogens - Part B
A2 - Marchi, Saverio
A2 - Galluzzi, Lorenzo
PB - Elsevier Inc.
ER -