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Frontiers in Cellular and Infection... 2017A common strategy among intracellular bacterial pathogens is to enter into a vacuolar environment upon host cell invasion. One such pathogen, , resides within the... (Review)
Review
A common strategy among intracellular bacterial pathogens is to enter into a vacuolar environment upon host cell invasion. One such pathogen, , resides within the -containing vacuole (SCV) inside epithelial cells and macrophages. hijacks the host endosomal system to establish this unique intracellular replicative niche, forming a highly complex and dynamic network of -induced filaments (SIFs). SIFs radiate outwards from the SCV upon onset of bacterial replication. SIF biogenesis is dependent on the activity of bacterial effector proteins secreted by the -pathogenicity island-2 (SPI-2) encoded type III secretion system. While the presence of SIFs has been known for almost 25 years, their precise role during infection remains elusive. This review summarizes our current knowledge of SCV maturation and SIF biogenesis, and recent advances in our understanding of the role of SIFs inside cells.
Topics: Animals; Cytoskeleton; Epithelial Cells; Host-Pathogen Interactions; Humans; Macrophages; Salmonella enterica; Vacuoles
PubMed: 28791257
DOI: 10.3389/fcimb.2017.00335 -
Cell Host & Microbe Feb 2022Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We...
Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We find intracellular pathogens solve this dilemma by using virulence factors to generate a complement-dependent find-me signal that initiates uptake by a new phagocyte through efferocytosis. During macrophage death, Salmonella uses a type III secretion system to perforate the membrane of the pathogen-containing vacuole (PCV), thereby triggering complement deposition on bacteria entrapped in pore-induced intracellular traps (PITs). In turn, complement activation signals neutrophil efferocytosis, a process that shelters intracellular bacteria from the respiratory burst. Similarly, Brucella employs its type IV secretion system to perforate the PCV membrane, which induces complement deposition on bacteria entrapped in PITs. Collectively, this work identifies virulence factor-induced perforation of the PCV as a strategy of intracellular pathogens to generate a find-me signal for efferocytosis.
Topics: Phagocytosis; Type III Secretion Systems; Type IV Secretion Systems; Vacuoles; Virulence Factors
PubMed: 34951948
DOI: 10.1016/j.chom.2021.12.001 -
ELife Mar 2024Membrane contact sites (MCSs) are junctures that perform important roles including coordinating lipid metabolism. Previous studies have indicated that vacuolar...
Membrane contact sites (MCSs) are junctures that perform important roles including coordinating lipid metabolism. Previous studies have indicated that vacuolar fission/fusion processes are coupled with modifications in the membrane lipid composition. However, it has been still unclear whether MCS-mediated lipid metabolism controls the vacuolar morphology. Here, we report that deletion of tricalbins (Tcb1, Tcb2, and Tcb3), tethering proteins at endoplasmic reticulum (ER)-plasma membrane (PM) and ER-Golgi contact sites, alters fusion/fission dynamics and causes vacuolar fragmentation in the yeast . In addition, we show that the sphingolipid precursor phytosphingosine (PHS) accumulates in tricalbin-deleted cells, triggering the vacuolar division. Detachment of the nucleus-vacuole junction (NVJ), an important contact site between the vacuole and the perinuclear ER, restored vacuolar morphology in both cells subjected to high exogenous PHS and Tcb3-deleted cells, supporting that PHS transport across the NVJ induces vacuole division. Thus, our results suggest that vacuolar morphology is maintained by MCSs through the metabolism of sphingolipids.
Topics: Mitochondrial Membranes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Vacuoles; Sphingolipids; Lipid Metabolism; Cell Membrane
PubMed: 38536872
DOI: 10.7554/eLife.89938 -
Plant, Cell & Environment May 2016Plant cells orchestrate an array of molecular mechanisms for maintaining plasmatic concentrations of essential heavy metal (HM) ions, for example, iron, zinc and copper,... (Review)
Review
Plant cells orchestrate an array of molecular mechanisms for maintaining plasmatic concentrations of essential heavy metal (HM) ions, for example, iron, zinc and copper, within the optimal functional range. In parallel, concentrations of non-essential HMs and metalloids, for example, cadmium, mercury and arsenic, should be kept below their toxicity threshold levels. Vacuolar compartmentalization is central to HM homeostasis. It depends on two vacuolar pumps (V-ATPase and V-PPase) and a set of tonoplast transporters, which are directly driven by proton motive force, and primary ATP-dependent pumps. While HM non-hyperaccumulator plants largely sequester toxic HMs in root vacuoles, HM hyperaccumulators usually sequester them in leaf cell vacuoles following efficient long-distance translocation. The distinct strategies evolved as a consequence of organ-specific differences particularly in vacuolar transporters and in addition to distinct features in long-distance transport. Recent molecular and functional characterization of tonoplast HM transporters has advanced our understanding of their contribution to HM homeostasis, tolerance and hyperaccumulation. Another important part of the dynamic vacuolar sequestration syndrome involves enhanced vacuolation. It involves vesicular trafficking in HM detoxification. The present review provides an updated account of molecular aspects that contribute to the vacuolar compartmentalization of HMs.
Topics: Cell Compartmentation; Inactivation, Metabolic; Metals, Heavy; Plants; Proton Pumps; Vacuoles
PubMed: 26729300
DOI: 10.1111/pce.12706 -
Trends in Parasitology Feb 2020When a malaria parasite invades a host erythrocyte it pushes itself in and invaginates a portion of the host membrane, thereby sealing itself inside and establishing... (Review)
Review
When a malaria parasite invades a host erythrocyte it pushes itself in and invaginates a portion of the host membrane, thereby sealing itself inside and establishing itself in the resulting vacuole. The parasitophorous vacuolar membrane (PVM) that surrounds the parasite is modified by the parasite, using its secretory organelles. To survive within this enveloping membrane, the organism must take in nutrients, secrete wastes, export proteins into the host cell, and eventually egress. Here, we review current understanding of the unique solutions Plasmodium has evolved to these challenges and discuss the remaining questions.
Topics: Erythrocytes; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Vacuoles
PubMed: 31866184
DOI: 10.1016/j.pt.2019.11.006 -
Current Opinion in Microbiology Apr 2020Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably... (Review)
Review
Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably stable, facilitating microbial replication and preventing exposure to host cytoplasmically localized innate immune sensing mechanisms. To maintain integrity of the membrane compartment, the pathogen is armed with defensive weapons that prevent loss of vacuole integrity and potential exposure to host innate signaling. In some cases, the microbial components that maintain vacuolar integrity have been identified, but the basis for why the compartment degrades in their absence is unclear. In this review, we point out that lessons from the microbial-programmed degradation of the vacuole by the cytoplasmically localized Shigella flexneri provide crucial insights into how degradation of pathogen vacuoles occurs. We propose that in the absence of bacterial-encoded guard proteins, aberrant trafficking of host membrane-associated components results in a dysfunctional pathogen compartment. As a consequence, the vacuole is poisoned and replication is terminated.
Topics: Autophagy; Bacterial Proteins; Chlamydia trachomatis; Gram-Negative Bacteria; Host-Pathogen Interactions; Humans; Legionella pneumophila; Multiprotein Complexes; Shigella flexneri; Sorting Nexins; Vacuoles; Virulence Factors
PubMed: 32044688
DOI: 10.1016/j.mib.2020.01.008 -
Archives of Razi Institute Jun 2023(), the etiological agent of the Q fever disease, ranks among the most sporadic and persistent global public health concerns. Ruminants are the principal source of... (Review)
Review
(), the etiological agent of the Q fever disease, ranks among the most sporadic and persistent global public health concerns. Ruminants are the principal source of human infections and diseases present in both acute and chronic forms. This bacterium is an intracellular pathogen that can survive and reproduce under acidic (pH 4 to 5) and harsh circumstances that contain -containing vacuoles. By undermining the autophagy defense system of the host cell, is able to take advantage of the autophagy pathway, which allows it to improve the movement of nutrients and the membrane, thereby extending the vacuole of the reproducing bacteria. For this method to work, it requires the participation of many bacterial effector proteins. In addition, the precise and prompt identification of the causative agent of an acute disease has the potential to delay the onset of its chronic form. Moreover, to make accurate and rapid diagnoses, it is necessary to create diagnostic devices. This review summarizes the most recent research on the epidemiology, pathogenesis, and diagnosis approaches of . This study also explored the complicated relationships between and the autophagic pathway, which are essential for intracellular reproduction and survival in host cells for the infection to be effective.
Topics: Humans; Coxiella burnetii; Q Fever; Vacuoles; Autophagy
PubMed: 38028822
DOI: 10.22092/ARI.2023.361161.2636 -
Cellular Microbiology Dec 2017Most bacterial pathogens enter and exit eukaryotic cells during their journey through the vertebrate host. In order to endure inside a eukaryotic cell, bacterial... (Review)
Review
Most bacterial pathogens enter and exit eukaryotic cells during their journey through the vertebrate host. In order to endure inside a eukaryotic cell, bacterial invaders commonly employ bacterial secretion systems to inject host cells with virulence factors that co-opt the host's membrane trafficking systems and thereby establish specialised pathogen-containing vacuoles (PVs) as intracellular niches permissive for microbial growth and survival. To defend against these microbial adversaries hiding inside PVs, host organisms including humans evolved an elaborate cell-intrinsic armoury of antimicrobial weapons that include noxious gases, antimicrobial peptides, degradative enzymes, and pore-forming proteins. This impressive defence machinery needs to be accurately delivered to PVs, in order to fight off vacuole-dwelling pathogens. Here, I discuss recent evidence that the presence of bacterial secretion systems at PVs and the associated destabilisation of PV membranes attract such antimicrobial delivery systems consisting of sugar-binding galectins as well as dynamin-like guanylate-binding proteins (GBPs). I will review recent advances in our understanding of intracellular immune recognition of PVs by galectins and GBPs, discuss how galectins and GBPs control host defence, and highlight important avenues of future research in this exciting area of cell-autonomous immunity.
Topics: Animals; Bacteria; GTP-Binding Proteins; Galectins; Humans; Immunologic Factors; Intracellular Membranes; Vacuoles
PubMed: 28973783
DOI: 10.1111/cmi.12793 -
The Journal of Cell Biology Mar 2020Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here,...
Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here, we discovered that starvation and TORC1 inactivation not only lead to the up-regulation of autophagy and vacuole proteins involved in recycling but also result in the down-regulation of many vacuole membrane proteins to supply amino acids as part of a vacuole remodeling process. Down-regulation of vacuole membrane proteins is initiated by ubiquitination, which is accomplished by the coordination of multiple E3 ubiquitin ligases, including Rsp5, the Dsc complex, and a newly characterized E3 ligase, Pib1. The Dsc complex is negatively regulated by TORC1 through the Rim15-Ume6 signaling cascade. After ubiquitination, vacuole membrane proteins are sorted into the lumen for degradation by ESCRT-dependent microautophagy. Thus, our study uncovered a complex relationship between TORC1 inactivation and vacuole biogenesis.
Topics: Endosomal Sorting Complexes Required for Transport; Intracellular Membranes; Microautophagy; Protein Kinases; Protein Transport; Proteolysis; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Time Factors; Transcription Factors; Ubiquitin; Ubiquitin-Protein Ligase Complexes; Ubiquitination; Vacuoles
PubMed: 32045480
DOI: 10.1083/jcb.201902127 -
Methods (San Diego, Calif.) Mar 2015Macroautophagy (hereafter autophagy) is a highly evolutionarily conserved process essential for sustaining cellular integrity, homeostasis, and survival. Most eukaryotic... (Review)
Review
Macroautophagy (hereafter autophagy) is a highly evolutionarily conserved process essential for sustaining cellular integrity, homeostasis, and survival. Most eukaryotic cells constitutively undergo autophagy at a low basal level. However, various stimuli, including starvation, organelle deterioration, stress, and pathogen infection, potently upregulate autophagy. The hallmark morphological feature of autophagy is the formation of the double-membrane vesicle known as the autophagosome. In yeast, flux through the pathway culminates in autophagosome-vacuole fusion, and the subsequent degradation of the resulting autophagic bodies and cargo by vacuolar hydrolases, followed by efflux of the breakdown products. Importantly, aberrant autophagy is associated with diverse human pathologies. Thus, there is a need for ongoing work in this area to further understand the cellular factors regulating this process. The field of autophagy research has grown exponentially in recent years, and although numerous model organisms are being used to investigate autophagy, the baker's yeast Saccharomyces cerevisiae remains highly relevant, as there are significant and unique benefits to working with this organism. In this review, we will focus on the current methods available to evaluate and monitor autophagy in S. cerevisiae, which in several cases have also been subsequently exploited in higher eukaryotes.
Topics: Autophagy; Autophagy-Related Protein 8 Family; Humans; Hydrolases; Microtubule-Associated Proteins; Phagosomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Vacuoles
PubMed: 25526918
DOI: 10.1016/j.ymeth.2014.12.008