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Frontiers in Cellular and Infection... 2015Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and... (Review)
Review
Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.
Topics: Bacterial Physiological Phenomena; Host-Pathogen Interactions; Humans; Intracellular Membranes; Mass Spectrometry; Proteome; Proteomics; Vacuoles
PubMed: 26082896
DOI: 10.3389/fcimb.2015.00048 -
Trends in Biochemical Sciences Jun 2019In eukaryotes, organelles and vesicles modulate their contents and identities through highly regulated membrane fusion events. Membrane trafficking and fusion are... (Review)
Review
In eukaryotes, organelles and vesicles modulate their contents and identities through highly regulated membrane fusion events. Membrane trafficking and fusion are carried out through a series of stages that lead to the formation of SNARE complexes between cellular compartment membranes to trigger fusion. Although the protein catalysts of membrane fusion are well characterized, their response to their surrounding microenvironment, provided by the lipid composition of the membrane, remains to be fully understood. Membranes are composed of bulk lipids (e.g., phosphatidylcholine), as well as regulatory lipids that undergo constant modifications by kinases, phosphatases, and lipases. These lipids include phosphoinositides, diacylglycerol, phosphatidic acid, and cholesterol/ergosterol. Here we describe the roles of these lipids throughout the stages of yeast vacuole homotypic fusion.
Topics: Cholesterol; Ergosterol; Glycerides; Humans; Membrane Fusion; Phosphatidic Acids; Phosphatidylinositols; Vacuoles
PubMed: 30587414
DOI: 10.1016/j.tibs.2018.12.003 -
Journal of Experimental Botany Jun 2017
Topics: Homeostasis; Membrane Transport Proteins; Membranes; Plant Physiological Phenomena; Plant Proteins; Vacuoles
PubMed: 28899083
DOI: 10.1093/jxb/erx229 -
Cell Host & Microbe Jun 2009Many intracellular pathogens survive in vacuolar niches composed of host-derived membranes modified extensively by pathogen proteins and lipids. Although intracellular... (Review)
Review
Many intracellular pathogens survive in vacuolar niches composed of host-derived membranes modified extensively by pathogen proteins and lipids. Although intracellular lifestyles offer protection from humoral immune responses, vacuole-bound pathogens nevertheless face powerful intracellular innate immune surveillance pathways that can trigger fusion with lysosomes, autophagy, and host cell death. Strategies used by vacuole-bound pathogens to invade and establish a replicative vacuole are well described, but how the integrity and stability of these parasitic vacuoles are maintained is poorly understood. Here, we identify potential mechanisms of pathogenic vacuole maintenance and the consequences of vacuole disruption by highlighting select bacterial and protozoan parasites.
Topics: Animals; Bacterial Physiological Phenomena; Eukaryota; Host-Pathogen Interactions; Models, Biological; Vacuoles
PubMed: 19527886
DOI: 10.1016/j.chom.2009.05.014 -
Bioarchitecture 2013The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord... (Review)
Review
The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord is composed of two cell layers: an outer epithelial-like sheath, and an inner core of cells that contain large fluid-filled vacuoles. We have recently shown these notochord vacuoles are lysosome-related organelles that form through Rab32a and vacuolar-type proton-ATPase-dependent acidification. Disruption of notochord vacuoles results in a shortened embryo along the anterior-posterior axis. Interestingly, we discovered that notochord vacuoles are also essential for proper spine morphogenesis and that vacuole defects lead to scoliosis of the spine. Here we discuss the cellular organization of the notochord and how key features of its architecture allow the notochord to function in embryonic axis elongation and spine formation.
Topics: Animals; Embryonic Development; Humans; Notochord; Vacuoles
PubMed: 23887209
DOI: 10.4161/bioa.25503 -
Trends in Microbiology Aug 2022Invasive bacteria colonise their host tissues by establishing niches inside eukaryotic cells, where they grow either in the cytosol or inside a specialised vacuole.... (Review)
Review
Invasive bacteria colonise their host tissues by establishing niches inside eukaryotic cells, where they grow either in the cytosol or inside a specialised vacuole. These two distinct intracellular lifestyles both present benefits but also impose various constraints on pathogenic microorganisms, in terms of nutrient acquisition, space requirements, exposure to immune responses, and ability to disseminate. Here we review the major characteristics of cytosolic and vacuolar lifestyles and the strategies used by bacteria to overcome challenges specific to each compartment. Recent research providing evidence that these scenarios are not mutually exclusive is presented, with the dual lifestyles of two foodborne pathogens, Listeria monocytogenes and Salmonella Typhimurium, discussed in detail. Finally, we elaborate on the conceptual implications of polyvalence from the perspective of host-pathogen interactions.
Topics: Cytosol; Host-Pathogen Interactions; Listeria monocytogenes; Salmonella typhimurium; Vacuoles
PubMed: 35168833
DOI: 10.1016/j.tim.2022.01.015 -
International Journal of Medical... Jan 2018Guanylate-binding proteins (GBP) are a family of dynamin-related large GTPases which are expressed in response to interferons and other pro-inflammatory cytokines. GBPs... (Review)
Review
Guanylate-binding proteins (GBP) are a family of dynamin-related large GTPases which are expressed in response to interferons and other pro-inflammatory cytokines. GBPs mediate a broad spectrum of innate immune functions against intracellular pathogens ranging from viruses to bacteria and protozoa. Several binding partners for individual GBPs have been identified and several different mechanisms of action have been proposed depending on the organisms, the cell type and the pathogen used. Many of these anti-pathogenic functions of GBPs involve the recruitment to and the subsequent destruction of pathogen containing vacuolar compartments, the assembly of large oligomeric innate immune complexes such as the inflammasome, or the induction of autophagy. Furthermore, GBPs often cooperate with immunity-related GTPases (IRGs), another family of dynamin-related GTPases, to exert their anti-pathogenic function, but since most IRGs have been lost in the evolution of higher primates, the anti-pathogenic function of human GBPs seems to be IRG-independent. GBPs and IRGs share biochemical and structural properties with the other members of the dynamin superfamily such as low nucleotide affinity and a high intrinsic GTPase activity which can be further enhanced by oligomerisation. Furthermore, GBPs and IRGs can interact with lipid membranes. In the case of three human and murine GBP isoforms this interaction is mediated by C-terminal isoprenylation. Based on cell biological studies, and in analogy to the function of other dynamins in membrane scission events, it has been postulated that both GBPs and IRGs might actively disrupt the outer membrane of pathogen-containing vacuole leading to the detection and destruction of the pathogen by the cytosolic innate immune system of the host. Recent evidence, however, indicates that GBPs might rather function by mediating membrane tethering events similar to the dynamin-related atlastin and mitofusin proteins, which mediate fusion of the ER and mitochondria, respectively. The aim of this review is to highlight the current knowledge on the function of GBPs in innate immunity and to combine it with the recent progress in the biochemical characterisation of this protein family.
Topics: Animals; Autophagy; Cytoplasm; GTP Phosphohydrolases; GTP-Binding Proteins; Humans; Immunity, Innate; Inflammasomes; Interferons; Vacuoles
PubMed: 29174633
DOI: 10.1016/j.ijmm.2017.10.013 -
Plant Signaling & Behavior Dec 2010As plants lack immune cells, each cell has to defend itself against invading pathogens. Plant cells have a large central vacuole that accumulates a variety of hydrolytic... (Review)
Review
As plants lack immune cells, each cell has to defend itself against invading pathogens. Plant cells have a large central vacuole that accumulates a variety of hydrolytic enzymes and antimicrobial compounds, raising the possibility that vacuoles play a role in plant defense. However, how plants use vacuoles to protect against invading pathogens is poorly understood. Recently, we characterized two vacuole-mediated defense strategies associated with programmed cell death (PCD). In one strategy, vacuolar processing enzyme (VPE) mediated the disruption of the vacuolar membrane, resulting in the release of vacuolar contents into the cytoplasm in response to viral infection. In the other strategy, proteasome-dependent fusion of the central vacuole with the plasma membrane caused the discharge of vacuolar antibacterial protease and cell death-promoting contents from the cell in response to bacterial infection. Intriguingly, both strategies relied on enzymes with caspase-like activities: the vacuolar membrane-collapse system required VPE, which has caspase-1-like activity, and the membrane-fusion system required a proteasome that has caspase-3-like activity. Thus, plants may have evolved a cellular immune system that involves vacuolar membrane collapse to prevent the systemic spread of viral pathogens, and membrane fusion to inhibit the proliferation of bacterial pathogens.
Topics: Cell Death; Intracellular Membranes; Membrane Fusion; Plant Cells; Plants; Vacuoles
PubMed: 21512325
DOI: 10.4161/psb.5.12.13319 -
Cell Death and Differentiation Aug 2011Almost all plant cells have large vacuoles that contain both hydrolytic enzymes and a variety of defense proteins. Plants use vacuoles and vacuolar contents for... (Review)
Review
Almost all plant cells have large vacuoles that contain both hydrolytic enzymes and a variety of defense proteins. Plants use vacuoles and vacuolar contents for programmed cell death (PCD) in two different ways: for a destructive way and for a non-destructive way. Destruction is caused by vacuolar membrane collapse, followed by the release of vacuolar hydrolytic enzymes into the cytosol, resulting in rapid and direct cell death. The destructive way is effective in the digestion of viruses proliferating in the cytosol, in susceptible cell death induced by fungal toxins, and in developmental cell death to generate integuments (seed coats) and tracheary elements. On the other hand, the non-destructive way involves fusion of the vacuolar and the plasma membrane, which allows vacuolar defense proteins to be discharged into the extracellular space where the bacteria proliferate. Membrane fusion, which is normally suppressed, was triggered in a proteasome-dependent manner. Intriguingly, both ways use enzymes with caspase-like activity; the membrane-fusion system uses proteasome subunit PBA1 with caspase-3-like activity, and the vacuolar-collapse system uses vacuolar processing enzyme (VPE) with caspase-1-like activity. This review summarizes two different ways of vacuole-mediated PCD and discusses how plants use them to attack pathogens that invade unexpectedly.
Topics: Cell Death; Membrane Fusion; Plant Cells; Plant Immunity; Plant Proteins; Plants; Proteasome Endopeptidase Complex; Vacuoles
PubMed: 21637288
DOI: 10.1038/cdd.2011.70 -
Microbiology and Molecular Biology... Mar 1998Delivery of proteins to the vacuole of the yeast Saccharomyces cerevisiae provides an excellent model system in which to study vacuole and lysosome biogenesis and... (Review)
Review
Delivery of proteins to the vacuole of the yeast Saccharomyces cerevisiae provides an excellent model system in which to study vacuole and lysosome biogenesis and membrane traffic. This organelle receives proteins from a number of different routes, including proteins sorted away from the secretory pathway at the Golgi apparatus and endocytic traffic arising from the plasma membrane. Genetic analysis has revealed at least 60 genes involved in vacuolar protein sorting, numerous components of a novel cytoplasm-to-vacuole transport pathway, and a large number of proteins required for autophagy. Cell biological and biochemical studies have provided important molecular insights into the various protein delivery pathways to the yeast vacuole. This review describes the various pathways to the vacuole and illustrates how they are related to one another in the vacuolar network of S. cerevisiae.
Topics: Biological Transport; Endocytosis; Saccharomyces cerevisiae; Vacuoles
PubMed: 9529893
DOI: 10.1128/MMBR.62.1.230-247.1998