host cell cytoplasm
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2022 ◽  
Vol 18 (1) ◽  
pp. e1010166
Author(s):  
Thao Thanh Tran ◽  
Carmen D. Mathmann ◽  
Marcela Gatica-Andrades ◽  
Rachel F. Rollo ◽  
Melanie Oelker ◽  
...  

A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.


2021 ◽  
Vol 22 (11) ◽  
pp. 5412
Author(s):  
Anastasia D Gazi ◽  
Michael Kokkinidis ◽  
Vasiliki E Fadouloglou

Type III Secretion Systems (T3SSs) are multicomponent nanomachines located at the cell envelope of Gram-negative bacteria. Their main function is to transport bacterial proteins either extracellularly or directly into the eukaryotic host cell cytoplasm. Type III Secretion effectors (T3SEs), latest to be secreted T3S substrates, are destined to act at the eukaryotic host cell cytoplasm and occasionally at the nucleus, hijacking cellular processes through mimicking eukaryotic proteins. A broad range of functions is attributed to T3SEs, ranging from the manipulation of the host cell’s metabolism for the benefit of the bacterium to bypassing the host’s defense mechanisms. To perform this broad range of manipulations, T3SEs have evolved numerous novel folds that are compatible with some basic requirements: they should be able to easily unfold, pass through the narrow T3SS channel, and refold to an active form when on the other side. In this review, the various folds of T3SEs are presented with the emphasis placed on the functional and structural importance of α-helices and helical domains.


2021 ◽  
Author(s):  
Vorrapon Chaikeeratisak ◽  
Kanika Khanna ◽  
Katrina T. Nguyen ◽  
MacKennon E. Egan ◽  
Eray Enustun ◽  
...  

SummaryMany eukaryotic viruses assemble mature particles within distinct subcellular compartments, but bacteriophages were long assumed to assemble randomly throughout the host cell cytoplasm. Here we visualized the subcellular location of viral particles formed during replication of Pseudomonas nucleus-forming jumbo phages and discovered that they assemble a unique structure inside cells we term phage bouquets. We show that after capsids complete DNA packaging at the surface of the phage nucleus, tails assemble and attach to the capsids, and these particles accumulate to form bouquets at specific subcellular locations. In these bouquets, the viral particles are arranged in a spherical pattern with tails oriented inward and the heads outwards. Localized at fixed distances on either side of the phage nucleus, bouquets grow in size and number over time as new phage particles are added. In the presence of mutations that cause the phage nucleus to be mispositioned away from its typical position at the midcell, bouquets still localize at the same fixed distance from the nucleus, suggesting an active mechanism for their formation and positioning. These results mark the discovery of a pathway for organizing mature viral particles inside bacteria and demonstrate that nucleus-forming jumbo phage, like most eukaryotic viruses, are highly spatially organized during all stages of their lytic cycle.


Author(s):  
Kerry Woods ◽  
Carmen Perry ◽  
Francis Brühlmann ◽  
Philipp Olias

One of the first events that follows invasion of leukocytes by Theileria sporozoites is the destruction of the surrounding host cell membrane and the rapid association of the intracellular parasite with host microtubules. This is essential for the parasite to establish its niche within the cytoplasm of the invaded leukocyte and sets Theileria spp. apart from other members of the apicomplexan phylum such as Toxoplasma gondii and Plasmodium spp., which reside within the confines of a host-derived parasitophorous vacuole. After establishing infection, transforming Theileria species (T. annulata, T. parva) significantly rewire the signaling pathways of their bovine host cell, causing continual proliferation and resistance to ligand-induced apoptosis, and conferring invasive properties on the parasitized cell. Having transformed its target cell, Theileria hijacks the mitotic machinery to ensure its persistence in the cytoplasm of the dividing cell. Some of the parasite and bovine proteins involved in parasite-microtubule interactions have been fairly well characterized, and the schizont expresses at least two proteins on its membrane that contain conserved microtubule binding motifs. Theileria-encoded proteins have been shown to be translocated to the host cell cytoplasm and nucleus where they have the potential to directly modify signaling pathways and host gene expression. However, little is known about their mode of action, and even less about how these proteins are secreted by the parasite and trafficked to their target location. In this review we explore the strategies employed by Theileria to transform leukocytes, from sporozoite invasion until immortalization of the host cell has been established. We discuss the recent description of nuclear pore-like complexes that accumulate on membranes close to the schizont surface. Finally, we consider putative mechanisms of protein and nutrient exchange that might occur between the parasite and the host. We focus in particular on differences and similarities with recent discoveries in T. gondii and Plasmodium species.


2021 ◽  
Vol 85 (1) ◽  
Author(s):  
R. Martin Roop ◽  
Ian S. Barton ◽  
Dariel Hopersberger ◽  
Daniel W. Martin

SUMMARY Bacteria in the genus Brucella are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world’s most common zoonoses. Brucella strains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals. The brucellae maintain predominantly an intracellular lifestyle in their mammalian hosts, and their ability to subvert the host immune response and survive and replicate in macrophages and placental trophoblasts underlies their success as pathogens. We are just beginning to understand how these bacteria evolved from a progenitor alphaproteobacterium with an environmental niche and diverged to become highly host-adapted and host-specific pathogens. Two important virulence determinants played critical roles in this evolution: (i) a type IV secretion system that secretes effector molecules into the host cell cytoplasm that direct the intracellular trafficking of the brucellae and modulate host immune responses and (ii) a lipopolysaccharide moiety which poorly stimulates host inflammatory responses. This review highlights what we presently know about how these and other virulence determinants contribute to Brucella pathogenesis. Gaining a better understanding of how the brucellae produce disease will provide us with information that can be used to design better strategies for preventing brucellosis in animals and for preventing and treating this disease in humans.


2021 ◽  
Author(s):  
Valerie Oriol Mathieu ◽  
Mark van Ooij ◽  
Kerstin Lühn ◽  
Jeff Stoddard

Viral vector vaccines use harmless, non-replicating or replicating viruses to deliver genetic material for production of vaccine antigens into host cell cytoplasm. While viral vector vaccines may theoretically induce life-long immunity with low antigen concentrations, their attenuation, safety and spread to the community are of concern. Vaccines based on recombinant viral vectors can induce both humoral and cellular immune responses. Adenovirus vectors are versatile gene transfer vectors that can be easily manufactured, and which may allow simultaneous expression of multiple antigens by a single vector construct. Adenovirus vector vaccines based on the adenovirus Ad26 vector have been widely used as vaccines against Ebola and COVID19 (see Chapters 44 and 56). A common concern of using viral vector vaccines is pre-existing immunity or induction of immunity against the vector itself, but in some circumstances it has no meaningful impact and it can be resolved in several ways. Several harmless viruses are already used as vectors for innovative vaccines and many more are in research.


Parasitology ◽  
2020 ◽  
Vol 147 (13) ◽  
pp. 1461-1468
Author(s):  
Onur Tosun

AbstractIn this study, a microsporidian pathogen of the date moth (Apomyelois (Ectomyelois) ceratoniae, Zeller, 1839) also known as the carob moth, is described based on light microscopy, ultrastructural characteristics and comparative molecular analysis. The pathogen infects the gut and hemolymph of A. ceratoniae. All development stages are in direct contact with the host cell cytoplasm. Fresh spores with nuclei arranged in a diplokaryon are oval and measured 3.29 ± 0.23 μm (4.18–3.03 μm, n = 200) in length and 1.91 ± 0.23 μm (2.98–1.66 μm, n = 200) in width. Spores stained with Giemsa's stain measured 3.11 ± 0.31 μm (3.72–2.41 μm, n = 150) in length and 1.76 ± 0.23 μm (2.16–1.25 μm, n = 150) in width. Spores have an isofilar polar filament with 10-12 coils. An 1110 bp long alignment of the current microsporidium showed an SSU rRNA gene difference of only 0.0009, corresponding to >99.91% sequence similarity with Nosema fumiferanae, while RPB1 gene sequences were 98.03% similar within an alignment of 969 bp. All morphological, ultrastructural and molecular features indicate that the microsporidian pathogen of A. ceratoniae is the new isolate of the N. fumiferanae and is named here as Nosema fumiferanae TY61.


2020 ◽  
Author(s):  
GI McFadden ◽  
PR Gilson ◽  
Ian Sims

Chlorarachniophytes are amoeboid/flagellate eukaryotes that harbor reduced green algal endosymbionts. The carbohydrate stores of chlorarachniophyte algae have been investigated using methylation analysis to determine monosaccharide composition. An appreciable quantity of long chain β-1,3 glucan occurs in these algae. Immunogold electron microscopy using an antibody specific for β-1,3 glucans localized β-1,3 glucans within a vacuole in the host cell cytoplasm. The results suggest that photosynthate produced by the endosymbiont is stored by the host. Implications of the data for endosymbiosis are discussed.


2020 ◽  
Author(s):  
GI McFadden ◽  
PR Gilson ◽  
Ian Sims

Chlorarachniophytes are amoeboid/flagellate eukaryotes that harbor reduced green algal endosymbionts. The carbohydrate stores of chlorarachniophyte algae have been investigated using methylation analysis to determine monosaccharide composition. An appreciable quantity of long chain β-1,3 glucan occurs in these algae. Immunogold electron microscopy using an antibody specific for β-1,3 glucans localized β-1,3 glucans within a vacuole in the host cell cytoplasm. The results suggest that photosynthate produced by the endosymbiont is stored by the host. Implications of the data for endosymbiosis are discussed.


2020 ◽  
Vol 139 ◽  
pp. 15-23
Author(s):  
SRM Jones ◽  
H Ahonen ◽  
J Taskinen

Infections with microsporidian parasites are described in skeletal muscle of burbot Lota lota from Lake Haukivesi, Finland. Infected myocytes contained spores within sporophorous vesicles (SPVs) in contact with host cell cytoplasm, similar to Pleistophora ladogensis in L. lota and smelt Osmerus eperlanus in western Russia and northern Germany. Analysis of small subunit ribosomal RNA (SSU rRNA) gene sequences indicated identity with Myosporidium spraguei in burbot and pike-perch from this lake. The latter is considered a junior synonym of P. ladogensis. Phylogenetic analysis of SSU rRNA sequences resolved the burbot parasite apart from a clade containing the type species P. typicalis, but together with M. merluccius. The parasite is renamed Myosporidium ladogensis (Voronin, 1978) n. comb. Networks of tubular appendages arising from developing meronts and SPVs were associated with degradation of host cell cytoplasm.


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