Nocardia species: host-parasite relationships.

The nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of nocardiae in neurodegenerative diseases in humans needs to be investigated.

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Tetraspanins are involved in Burkholderia pseudomallei-induced cell-to-cell fusion of phagocytic and non-phagocytic cells

Scientific Reports ◽

10.1038/s41598-020-74737-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tanes Sangsri ◽

Natnaree Saiprom ◽

Alisa Tubsuwan ◽

Peter Monk ◽

Lynda J. Partridge ◽

...

Keyword(s):

Burkholderia Pseudomallei ◽

Severe Disease ◽

A549 Cells ◽

Host Cells ◽

Phagocytic Cells ◽

Tropical Regions ◽

Cellular Factors ◽

Large Extracellular Loop

Abstract Tetraspanins are four-span transmembrane proteins of host cells that facilitate infections by many pathogens. Burkholderia pseudomallei is an intracellular bacterium and the causative agent of melioidosis, a severe disease in tropical regions. This study investigated the role of tetraspanins in B. pseudomallei infection. We used flow cytometry to determine tetraspanins CD9, CD63, and CD81 expression on A549 and J774A.1 cells. Their roles in B. pseudomallei infection were investigated in vitro using monoclonal antibodies (MAbs) and recombinant large extracellular loop (EC2) proteins to pretreat cells before infection. Knockout of CD9 and CD81 in cells was performed using CRISPR Cas9 to confirm the role of tetraspanins. Pretreatment of A549 cells with MAb against CD9 and CD9-EC2 significantly enhanced B. pseudomallei internalization, but MAb against CD81 and CD81-EC2 inhibited MNGC formation. Reduction of MNGC formation was consistently observed in J774.A1 cells pretreated with MAbs specific to CD9 and CD81 and with CD9-EC2 and CD81-EC2. Data from knockout experiments confirmed that CD9 enhanced bacterial internalization and that CD81 inhibited MNGC formation. Our data indicate that tetraspanins are host cellular factors that mediated internalization and membrane fusion during B. pseudomallei infection. Tetraspanins may be the potential therapeutic targets for melioidosis.

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Adhesion of Tritrichomonas foetus to Bovine Vaginal Epithelial Cells

Infection and Immunity ◽

10.1128/iai.67.8.3847-3854.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 3847-3854 ◽

Cited By ~ 53

Author(s):

B. N. Singh ◽

J. J. Lucas ◽

D. H. Beach ◽

S. T. Shin ◽

R. O. Gilbert

Keyword(s):

Epithelial Cells ◽

Cell Surface ◽

Trichomonas Vaginalis ◽

Host Cells ◽

Tritrichomonas Foetus ◽

Trypan Blue Exclusion ◽

Vaginal Epithelial Cells ◽

Host Parasite

ABSTRACT An in vitro culture system of bovine vaginal epithelial cells (BVECs) was developed to study the cytopathogenic effects ofTritrichomonas foetus and the role of lipophosphoglycan (LPG)-like cell surface glycoconjugates in adhesion of parasites to host cells. Exposure of BVEC monolayers to T. foetusresulted in extensive damage of monolayers. Host cell disruption was measured quantitatively by a trypan blue exclusion assay and by release of 3H from [3H]thymidine-labeled host cells. Results indicated contact-dependent cytotoxicity of host cells byT. foetus. The cytopathogenic effect was a function ofT. foetus density. Metronidazole- or periodate-treatedT. foetus showed no damage to BVEC monolayers. A related human trichomonad, Trichomonas vaginalis, showed no cytotoxic effects, indicating species-specific host-parasite interactions. A direct binding assay was developed and used to investigate the role of a major cell surface LPG-like molecule in host-parasite adhesion. The results of competition experiments showed that the binding to BVECs was displaceable, was saturable, and yielded a typical binding curve, suggesting that specific receptor-ligand interactions mediate the attachment of T. foetus to BVECs. Progesterone-treated BVECs showed enhanced parasite binding. T. foetus LPG inhibited the binding of T. foetus to BVECs; the LPG from T. vaginalis and a variety of other glycoconjugates did not. These data imply specificity of LPG on host-parasite adhesion. Periodate-treated parasites showed no adherence to host cells, indicating the involvement of carbohydrate containing molecules in the adhesion process.

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Introduction: disease resistance in plants

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1972.0047 ◽

1972 ◽

Vol 181 (1064) ◽

pp. 213-232 ◽

Cited By ~ 7

Keyword(s):

Higher Plants ◽

Hypersensitive Reaction ◽

Host Cells ◽

Cell Wall Degrading Enzymes ◽

General Terms ◽

Bacteria And Fungi ◽

The One ◽

Almost All ◽

Host Parasite

This paper discusses in general terms the mechanisms proposed to explain the resistance of higher plants to infection and colonization by bacteria and fungi, especially the type of resistance associated with rapid killing of host cells and very limited growth of the pathogen; that is, with the hypersensitive reaction of the plant to infection (h.r.). The main points considered are: the significance of the h.r. for obligate and other types of parasites; the nature of the h.r. and the means by which it is invoked; the absence of the h.r in compatible host-parasite combinations; the h.r. and the production of phytoalexins, and the role of the latter in resistance; the part played by cell-wall degrading enzymes in the earliest stages of infection; the relation between the h.r. in interactions between races of a pathogen and different forms of a host species, on the one hand, and the resistance of all plants to almost all pathogens, on the other. Also discussed is the less specific but important type of resistance in which the pathogen continues to grow in resistant plants more slowly than in susceptible plants.

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Role of the Brucella suis Lipopolysaccharide O Antigen in Phagosomal Genesis and in Inhibition of Phagosome-Lysosome Fusion in Murine Macrophages

Infection and Immunity ◽

10.1128/iai.71.3.1481-1490.2003 ◽

2003 ◽

Vol 71 (3) ◽

pp. 1481-1490 ◽

Cited By ~ 101

Author(s):

Françoise Porte ◽

Aroem Naroeni ◽

Safia Ouahrani-Bettache ◽

Jean-Pierre Liautard

Keyword(s):

Molecular Mechanisms ◽

Cell Types ◽

Host Cells ◽

Phagocytic Cells ◽

Murine Macrophages ◽

O Antigen ◽

Brucella Suis ◽

Important Virulence Factor ◽

Membrane Bound

ABSTRACT Brucella species are gram-negative, facultative intracellular bacteria that infect humans and animals. These organisms can survive and replicate within a membrane-bound compartment inside professional and nonprofessional phagocytic cells. Inhibition of phagosome-lysosome fusion has been proposed as a mechanism for intracellular survival in both cell types. However, the molecular mechanisms and the microbial factors involved are poorly understood. Smooth lipopolysaccharide (LPS) of Brucella has been reported to be an important virulence factor, although its precise role in pathogenesis is not yet clear. In this study, we show that the LPS O side chain is involved in inhibition of the early fusion between Brucella suis-containing phagosomes and lysosomes in murine macrophages. In contrast, the phagosomes containing rough mutants, which fail to express the O antigen, rapidly fuse with lysosomes. In addition, we show that rough mutants do not enter host cells by using lipid rafts, contrary to smooth strains. Thus, we propose that the LPS O chain might be a major factor that governs the early behavior of bacteria inside macrophages.

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Evaluation of the role of CD47 in sickle cell disease

Journal of Hematopathology ◽

10.1007/s12308-020-00433-5 ◽

2021 ◽

Author(s):

Basmah Eldakhakhny ◽

Hadeel Al Sadoun ◽

Nehal Bin Taleb ◽

Dunya Ahmed Nori ◽

Nawal Helmi ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Annexin V ◽

Cell Disease ◽

Phagocytic Cells ◽

Surface Marker Expression ◽

Inflammatory Phenotype ◽

Healthy Control ◽

Cell Surface Marker Expression ◽

Pro Inflammatory Cytokines

AbstractCD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.

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A novel putative microtubule-associated protein is involved in arbuscule development during arbuscular mycorrhiza formation

Plant and Cell Physiology ◽

10.1093/pcp/pcaa159 ◽

2021 ◽

Author(s):

Tania Ho-Plágaro ◽

Raúl Huertas ◽

María I Tamayo-Navarrete ◽

Elison Blancaflor ◽

Nuria Gavara ◽

...

Keyword(s):

Plant Root ◽

Arbuscular Mycorrhizal ◽

Host Cells ◽

Root Cells ◽

Filament Dynamics ◽

Fungal Structure ◽

Genes Encoding ◽

Associated Proteins ◽

Mycorrhizal Development

Abstract The formation of arbuscular mycorrhizal (AM) symbiosis requires plant root host cells to undergo major structural and functional reprogramming in order to house the highly branched AM fungal structure for the reciprocal exchange of nutrients. These morphological modifications are associated with cytoskeleton remodelling. However, molecular bases and the role of microtubules (MTs) and actin filament dynamics during AM formation are largely unknown. In this study, the tomato tsb gene, belonging to a Solanaceae group of genes encoding MT-associated proteins for pollen development, was found to be highly expressed in root cells containing arbuscules. At earlier stages of mycorrhizal development, tsb overexpression enhanced the formation of highly developed and transcriptionally active arbuscules, while tsb silencing hampers the formation of mature arbuscules and represses arbuscule functionality. However, at later stages of mycorrhizal colonization, tsb OE roots accumulate fully developed transcriptionally inactive arbuscules, suggesting that the collapse and turnover of arbuscules might be impaired by TSB accumulation. Imaging analysis of the MT cytoskeleton in cortex root cells overexpressing tsb revealed that TSB is involved in MT-bundling. Taken together, our results provide unprecedented insights into the role of novel MT-associated protein in MT rearrangements throughout the different stages of the arbuscule life cycle.

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The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells

Scientific Reports ◽

10.1038/s41598-020-79593-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Harshini Weerasinghe ◽

Hayley E. Bugeja ◽

Alex Andrianopoulos

Keyword(s):

Pathogenic Fungi ◽

Host Cells ◽

Microbial Pathogens ◽

Mammalian Host ◽

Host Immune System ◽

Nucleotide Exchange ◽

Phagocytic Cells ◽

Macrophage Infection ◽

Bar Domain ◽

Talaromyces Marneffei

AbstractMicrobial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. marneffei that controls intracellular yeast morphogenesis.

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Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

International Journal of Molecular Sciences ◽

10.3390/ijms22115705 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5705

Author(s):

Karolina Szewczyk-Golec ◽

Marta Pawłowska ◽

Roland Wesołowski ◽

Marcin Wróblewski ◽

Celestyna Mila-Kierzenkowska

Keyword(s):

Oxidative Stress ◽

Animal Studies ◽

Treatment Options ◽

Natural Antioxidants ◽

Redox Status ◽

Host Cells ◽

Common Disease ◽

Parasite Viability

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

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Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽

10.3390/pathogens10060675 ◽

2021 ◽

Vol 10 (6) ◽

pp. 675

Author(s):

Samira Elmanfi ◽

Mustafa Yilmaz ◽

Wilson W. S. Ong ◽

Kofi S. Yeboah ◽

Herman O. Sintim ◽

...

Keyword(s):

Immune Response ◽

Periodontal Disease ◽

Innate Immune ◽

Host Cells ◽

Type I Interferons ◽

Type I ◽

Vaccine Adjuvants ◽

Cyclic Dinucleotides ◽

Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

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Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

Journal of Fungi ◽

10.3390/jof7020124 ◽

2021 ◽

Vol 7 (2) ◽

pp. 124

Author(s):

Charmaine Retanal ◽

Brianna Ball ◽

Jennifer Geddes-McAlister

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Treatment Options ◽

Global Scale ◽

Host Cells ◽

Candida Spp ◽

Post Translational Modifications ◽

Fungal Host ◽

Resistant Species

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.

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