Manipulation of Host Cell Organelles by Intracellular Pathogens

Abstract

Pathogenic intracellular bacteria, parasites and viruses have evolved sophisticated mechanisms to manipulate mammalian host cells to serve as niches for persistence and proliferation. The intracellular lifestyles of pathogens involve the manipulation of membrane-bound organellar compartments of host cells. In this review, we described how normal structural organization and cellular functions of endosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, or lipid droplets are targeted by microbial virulence mechanisms. We focus on the specific interactions of Salmonella, Legionella pneumophila, Rickettsia rickettsii, Chlamydia spp. and Mycobacterium tuberculosis representing intracellular bacterial pathogens, and of Plasmodium spp. and Toxoplasma gondii representing intracellular parasites. The replication strategies of various viruses, i.e., Influenza A virus, Poliovirus, Brome mosaic virus, Epstein-Barr Virus, Hepatitis C virus, severe acute respiratory syndrome virus (SARS), Dengue virus, Zika virus, and others are presented with focus on the specific manipulation of the organelle compartments. We compare the specific features of intracellular lifestyle and replication cycles, and highlight the communalities in mechanisms of manipulation deployed.

Insights Into the Biogenesis and Emerging Functions of Lipid Droplets From Unbiased Molecular Profiling Approaches

“…Reflecting an early conception of LDs as rather “passive” lipid storage sites, a model has long been held whereby several intracellular pathogens hijack and use these organelles as convenient sources of energy and building blocks for their replication, and have even developed specific mechanisms to induce and attract LDs ( van der Meer-Janssen et al, 2010 ; Kellermann et al, 2021 ). Among viral agents, a classical example is embodied by HCV: this RNA virus replicates at and is trafficked for exocytosis in close association to LDs, and its protein product HSV-NS5a induces LD biogenesis through activation of fatty acid synthase (FASN) and DGAT1—two key limiting enzymes in fatty acid de novo biosynthesis and triacylglycerol conjugation, respectively)—and LD tethering to replication factories through the RAB18 GTPase and accessory proteins such as Annexin A3 (ANXA3) ( Herker et al, 2010 ; Camus et al, 2013 ; Dansako et al, 2014 ; Loizides-Mangold et al, 2014 ).…”

High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium

“…Therefore, researchers have turned to transformed or immortalized cell lines to study intestinal epithelial infections in cultured proxies of the gut epithelium. These cell lines often fail to recapitulate key features of intestinal epithelial cell (IEC) layers, such as a densely packed polarized morphology, a microvilliated apical surface, and sensitivity to cell death mechanisms, but have nevertheless uncovered a wealth of information about pathogen infection cycles ( 1 – 6 ). In contrast, the impact of physiologically relevant host cell and tissue parameters on infection dynamics remains understudied.…”

Role of Host Small GTPases in Apicomplexan Parasite Infection

“…Apicomplexa also scavenge nutrients from the host cell [ 9 ] by subverting the host cell trafficking of nutrient-loaded vesicles and the subcellular localization of organelles involved in vesicle maturation and nutrients transport, such as the Golgi network and the endoplasmic reticulum [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

“…The modification of the host cell cytoskeleton is key to apicomplexan parasite survival, both during host cell invasion and the subsequent intracellular development. This manipulation is achieved either by a direct interaction between the parasite and the host cytoskeleton or by hijacking host signaling pathways involved in cytoskeleton regulation [ 13 , 20 ].…”