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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 -
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 -
Autophagy Feb 2014The morphometric examination of autophagic bodies provides useful information about the mechanism and magnitude of macroautophagy, and yeast researchers frequently... (Review)
Review
The morphometric examination of autophagic bodies provides useful information about the mechanism and magnitude of macroautophagy, and yeast researchers frequently utilize various measurements of these structures as part of their quantification of the process. The utility of this approach, however, has led to the common misconception that autophagic bodies can be found in the mammalian lysosome, which is generally not correct.
Topics: Animals; Autophagy; Humans; Lysosomes; Metabolic Networks and Pathways; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Vacuoles
PubMed: 24343261
DOI: 10.4161/auto.27367 -
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 -
Bioarchitecture 2013A vacuole is a membrane-bound subcellular structure involved in intracellular digestion. Instead of the large "vacuolar" organelles that are found in plants and fungi,... (Review)
Review
A vacuole is a membrane-bound subcellular structure involved in intracellular digestion. Instead of the large "vacuolar" organelles that are found in plants and fungi, animal cells possess lysosomes that are smaller in size and are enriched with hydrolytic enzymes similar to those found in the vacuoles. Large vacuolar structures are often observed in highly differentiated mammalian tissues such as embryonic visceral endoderm and absorbing epithelium. Vacuoles/lysosomes share a conserved mechanism of biogenesis, and they are at the terminal of the endocytic pathways, Recent genetic studies of the mammalian orthologs of Vam/Vps genes, which have essential functions for vacuole assembly, revealed that the dynamics of vacuoles/lysosomes are important for tissue differentiation and patterning through regulation of various molecular signaling events in mammals.
Topics: Animals; Embryonic Development; Humans; Mammals; Protein Transport; Vacuoles
PubMed: 23572040
DOI: 10.4161/bioa.24126 -
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 -
Cell Host & Microbe Sep 2013The ability to create and maintain a specialized organelle that supports bacterial replication is an important virulence property for many intracellular pathogens.... (Review)
Review
The ability to create and maintain a specialized organelle that supports bacterial replication is an important virulence property for many intracellular pathogens. Living in a membrane-bound vacuole presents inherent challenges, including the need to remodel a plasma membrane-derived organelle into a novel structure that will expand and provide essential nutrients to support replication, while also having the vacuole avoid membrane transport pathways that target bacteria for destruction in lysosomes. It is clear that pathogenic bacteria use different strategies to accomplish these tasks. The dynamics by which host Rab GTPases associate with pathogen-occupied vacuoles provide insight into the mechanisms used by different bacteria to manipulate host membrane transport. In this review we highlight some of the strategies bacteria use to maintain a pathogen-occupied vacuole by focusing on the Rab proteins involved in biogenesis and maintenance of these novel organelles.
Topics: Bacteria; Host-Pathogen Interactions; Inclusion Bodies; Models, Biological; Vacuoles; rab GTP-Binding Proteins
PubMed: 24034612
DOI: 10.1016/j.chom.2013.08.010 -
International Journal of Molecular... Jan 2023Vacuolar processing enzymes (VPEs) are plant cysteine proteases that are subjected to autoactivation in an acidic pH. It is presumed that VPEs, by activating other... (Review)
Review
Vacuolar processing enzymes (VPEs) are plant cysteine proteases that are subjected to autoactivation in an acidic pH. It is presumed that VPEs, by activating other vacuolar hydrolases, are in control of tonoplast rupture during programmed cell death (PCD). Involvement of VPEs has been indicated in various types of plant PCD related to development, senescence, and environmental stress responses. Another pathway induced during such processes is autophagy, which leads to the degradation of cellular components and metabolite salvage, and it is presumed that VPEs may be involved in the degradation of autophagic bodies during plant autophagy. As both PCD and autophagy occur under similar conditions, research on the relationship between them is needed, and VPEs, as key vacuolar proteases, seem to be an important factor to consider. They may even constitute a potential point of crosstalk between cell death and autophagy in plant cells. This review describes new insights into the role of VPEs in plant PCD, with an emphasis on evidence and hypotheses on the interconnections between autophagy and cell death, and indicates several new research opportunities.
Topics: Apoptosis; Plants; Vacuoles; Autophagy; Cell Death
PubMed: 36674706
DOI: 10.3390/ijms24021198