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Current Opinion in Microbiology Oct 2021During the vertebrate stage of the Plasmodium life cycle, obligate intracellular malaria parasites establish a vacuolar niche for replication, first within host... (Review)
Review
During the vertebrate stage of the Plasmodium life cycle, obligate intracellular malaria parasites establish a vacuolar niche for replication, first within host hepatocytes at the pre-patent liver-stage and subsequently in erythrocytes during the pathogenic blood-stage. Survival in this protective microenvironment requires diverse transport mechanisms that enable the parasite to transcend the vacuolar barrier. Effector proteins exported out of the vacuole modify the erythrocyte membrane, increasing access to serum nutrients which then cross the vacuole membrane through a nutrient-permeable channel, supporting rapid parasite growth. This review highlights the most recent insights into the organization of the parasite vacuole to facilitate the solute, lipid and effector protein trafficking that establishes a nutrition pipeline in the terminally differentiated, organelle-free red blood cell.
Topics: Erythrocytes; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Plasmodium falciparum; Protein Transport; Protozoan Proteins; Vacuoles
PubMed: 34375857
DOI: 10.1016/j.mib.2021.07.010 -
Nature Reviews. Microbiology Oct 2018
Topics: Nutrients; Plasmodium; Vacuoles
PubMed: 30177797
DOI: 10.1038/s41579-018-0081-5 -
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 -
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 -
International Journal of Medical... Jan 2018The environmental bacterium Legionella pneumophila replicates in free-living amoeba as well as in alveolar macrophages upon inhalation of bacteria-laden aerosols.... (Review)
Review
The environmental bacterium Legionella pneumophila replicates in free-living amoeba as well as in alveolar macrophages upon inhalation of bacteria-laden aerosols. Resistance of the opportunistic pathogen to macrophages is a prerequisite to cause a severe pneumonia called Legionnaires' disease. L. pneumophila grows intracellularly in a unique, ER-associated compartment, the Legionella-containing vacuole (LCV). The bacterial Icm/Dot type IV secretion system represents an essential virulence factor, which translocates approximately 300 "effector proteins" into protozoan or mammalian host cells. Some of these effectors contribute to the formation of the LCV by targeting conserved host factors implicated in membrane dynamics, such as phosphoinositide lipids and small GTPases. Here we review recent findings on the role of phosphoinositides, small and large GTPases as well as ER dynamics for pathogen vacuole formation and intracellular replication of L. pneumophila.
Topics: Amoeba; Animals; Bacterial Proteins; Endoplasmic Reticulum; GTP Phosphohydrolases; Host-Pathogen Interactions; Humans; Legionella; Macrophages; Phosphatidylinositols; Type IV Secretion Systems; Vacuoles
PubMed: 28865995
DOI: 10.1016/j.ijmm.2017.08.004 -
Current Opinion in Microbiology Feb 2019Pathogens have devised various strategies to alter the host endomembrane system towards building their replicative niche. This is aptly illustrated by Salmonella... (Review)
Review
Pathogens have devised various strategies to alter the host endomembrane system towards building their replicative niche. This is aptly illustrated by Salmonella Typhimurium, whereby it remodels the host endolysosomal system to form a unique niche, also known as Salmonella-containing vacuole (SCV). Decades of research using in vitro cell-based infection studies have revealed intricate details of how Salmonella effectors target endocytic trafficking machinery of the host cell to acquire membrane and nutrients for bacterial replication. Unexpectedly, Salmonella requires host factors involved in endosome-lysosome fusion for its intravacuolar replication. Understanding how Salmonella obtains selective content from lysosomes, that is nutrients, but not active hydrolases, needs further exploration. Recent studies have described heterogeneity in the composition and pH of lysosomes, which will be highly relevant to explore, not only in the context of Salmonella infection, but also for other intracellular pathogens that interact with the endolysosomal pathway.
Topics: Host-Pathogen Interactions; Lysosomes; Salmonella typhimurium; Vacuoles
PubMed: 30391777
DOI: 10.1016/j.mib.2018.10.003 -
Critical Reviews in Microbiology May 2022Membrane contact sites (MCSs) refer to the areas of close proximity between heterologous membranes. A growing body of evidence indicates that MCSs are involved in... (Review)
Review
Membrane contact sites (MCSs) refer to the areas of close proximity between heterologous membranes. A growing body of evidence indicates that MCSs are involved in important cellular functions, such as cellular material transfer, organelle biogenesis, and cell growth. Importantly, the study of MCSs at the bacteria-host interface is an emerging popular research topic. Intracellular bacterial pathogens have evolved a variety of fascinating strategies to interfere with MCSs by injecting effectors into infected host cells. Bacteria-containing vacuoles establish direct physical contact with organelles within the host, ensuring vacuolar membrane integrity and energy supply from host organelles and protecting the vacuoles from the host endocytic pathway and lysosomal degradation. An increasing number of bacterial effectors from various bacterial pathogens hijack components of host MCSs to form the vacuole-organelle MCSs for material exchange. MCS-related events have been identified as new mechanisms of microbial pathogenesis to greatly improve bacterial survival and replication within host cells. In this review, we will discuss the recent advances in MCSs at the bacteria-host interface, focussing on the roles of MCSs mediated by bacterial effectors in microbial pathogenesis.
Topics: Bacteria; Vacuoles
PubMed: 34403642
DOI: 10.1080/1040841X.2021.1961678 -
Nature Communications Apr 2021Synthesis and degradation of cellular constituents must be balanced to maintain cellular homeostasis, especially during adaptation to environmental stress. The role of...
Synthesis and degradation of cellular constituents must be balanced to maintain cellular homeostasis, especially during adaptation to environmental stress. The role of autophagy in the degradation of proteins and organelles is well-characterized. However, autophagy-mediated RNA degradation in response to stress and the potential preference of specific RNAs to undergo autophagy-mediated degradation have not been examined. In this study, we demonstrate selective mRNA degradation by rapamycin-induced autophagy in yeast. Profiling of mRNAs from the vacuole reveals that subsets of mRNAs, such as those encoding amino acid biosynthesis and ribosomal proteins, are preferentially delivered to the vacuole by autophagy for degradation. We also reveal that autophagy-mediated mRNA degradation is tightly coupled with translation by ribosomes. Genome-wide ribosome profiling suggested a high correspondence between ribosome association and targeting to the vacuole. We propose that autophagy-mediated mRNA degradation is a unique and previously-unappreciated function of autophagy that affords post-transcriptional gene regulation.
Topics: Autophagy; Blotting, Northern; RNA Stability; RNA, Fungal; RNA, Messenger; RNA-Seq; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Proteins; Ribosomes; Saccharomyces cerevisiae; Vacuoles
PubMed: 33875662
DOI: 10.1038/s41467-021-22574-6