scholarly journals What helminth genomes have taught us about parasite evolution

Parasitology ◽  
2014 ◽  
Vol 142 (S1) ◽  
pp. S85-S97 ◽  
Author(s):  
MAGDALENA ZAROWIECKI ◽  
MATT BERRIMAN
Keyword(s):  
Immune System ◽  
Antigenic Variation ◽  
Meta Analysis ◽  
Gene Families ◽  
Host Immune System ◽  
First Line ◽  
Parasite Evolution ◽  
Secretory Products ◽  
Parasitic Worms

SUMMARYThe genomes of more than 20 helminths have now been sequenced. Here we perform a meta-analysis of all sequenced genomes of nematodes and Platyhelminthes, and attempt to address the question of what are the defining characteristics of helminth genomes. We find that parasitic worms lack systems for surface antigenic variation, instead maintaining infections using their surfaces as the first line of defence against the host immune system, with several expanded gene families of genes associated with the surface and tegument. Parasite excretory/secretory products evolve rapidly, and proteases even more so, with each parasite exhibiting unique modifications of its protease repertoire. Endoparasitic flatworms show striking losses of metabolic capabilities, not matched by nematodes. All helminths do however exhibit an overall reduction in auxiliary metabolism (biogenesis of co-factors and vitamins). Overall, the prevailing pattern is that there are few commonalities between the genomes of independently evolved parasitic worms, with each parasite having undergone specific adaptations for their particular niche.

scholarly journals Peptidoglycan O-Acetylation as a Virulence Factor: Its Effect on Lysozyme in the Innate Immune System

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 94 ◽  
Author(s):  
Ashley S. Brott ◽  
Anthony J. Clarke
Keyword(s):  
Immune System ◽  
Virulence Factor ◽  
Innate Immune System ◽  
Innate Immune ◽  
Host Immune System ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Structural Support ◽  
Important Virulence Factor ◽  
Novel Target

The peptidoglycan sacculus of both Gram-positive and Gram-negative bacteria acts as a protective mesh and provides structural support around the entirety of the cell. The integrity of this structure is of utmost importance for cell viability and so naturally is the first target for attack by the host immune system during bacterial infection. Lysozyme, a muramidase and the first line of defense of the innate immune system, targets the peptidoglycan sacculus hydrolyzing the β-(1→4) linkage between repeating glycan units, causing lysis and the death of the invading bacterium. The O-acetylation of N-acetylmuramoyl residues within peptidoglycan precludes the productive binding of lysozyme, and in doing so renders it inactive. This modification has been shown to be an important virulence factor in pathogens such as Staphylococcus aureus and Neisseria gonorrhoeae and is currently being investigated as a novel target for anti-virulence therapies. This article reviews interactions made between peptidoglycan and the host immune system, specifically with respect to lysozyme, and how the O-acetylation of the peptidoglycan interrupts these interactions, leading to increased pathogenicity.

scholarly journals Cross-Reactive Immune Responses as Primary Drivers of Malaria Chronicity

2013 ◽  
Vol 82 (1) ◽  
pp. 140-151 ◽  
Author(s):  
Eili Y. Klein ◽  
Andrea L. Graham ◽  
Manuel Llinás ◽  
Simon Levin
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Malaria Infection ◽  
Antigenic Variation ◽  
Cross Reactivity ◽  
Primary Response ◽  
Small Subset ◽  
Host Immune System ◽  
Primary Role ◽  
Content Type

ABSTRACTThe within-host dynamics of an infection with the malaria parasitePlasmodium falciparumare the result of a complex interplay between the host immune system and parasite. Continual variation of theP. falciparumerythrocyte membrane protein (PfEMP1) antigens displayed on the surface of infected red blood cells enables the parasite to evade the immune system and prolong infection. Despite the importance of antigenic variation in generating the dynamics of infection, our understanding of the mechanisms by which antigenic variation generates long-term chronic infections is still limited. We developed a model to examine the role of cross-reactivity in generating infection dynamics that are comparable to those of experimental infections. The hybrid computational model we developed is attuned to the biology of malaria by mixing discrete replication events, which mimics the synchrony of parasite replication and invasion, with continuous interaction with the immune system. Using simulations, we evaluated the dynamics of a single malaria infection over time. We then examined three major mechanisms by which the dynamics of a malaria infection can be structured: cross-reactivity of the immune response to PfEMP1, differences in parasite clearance rates, and heterogeneity in the rate at which antigens switch. The results of our simulations demonstrate that cross-reactive immune responses play a primary role in generating the dynamics observed in experimentally untreated infections and in lengthening the period of infection. Importantly, we also find that it is the primary response to the initially expressed PfEMP1, or small subset thereof, that structures the cascading cross-immune dynamics and allows for elongation of the infection.

scholarly journals Chromodomain protein regulates the expression of a subset of RIFINs in P. falciparum

2021 ◽  
Author(s):  
Devadathan Valiyamangalath Sethumadhavan ◽  
Marta Tiburcio ◽  
Abhishek Kanyal ◽  
CA Jabeena ◽  
Gayathri Govindaraju ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune System ◽  
Virulence Genes ◽  
Gene Families ◽  
Host Immune System ◽  
Sequencing Analysis ◽  
Chip Sequencing ◽  
Conditional Deletion ◽  
Epigenetic Regulator ◽  
Variant Gene

AbstractPlasmodium falciparum expresses clonally variant proteins on the surface of infected erythrocytes to evade the host immune system. The clonally variant multigenes include var, rifin, and stevor, which express EMP1, RIFIN, and STEVOR proteins, respectively. The rifins are the largest multigene family and are essentially involved in the RBC rosetting, the hallmark of severe malaria. The regulators that control the RIFINs expression in P. falciparum have not been reported so far. This study reports a chromodomain-containing protein (PfCDP) that binds to H3K9me3 modification on P. falciparum chromatin. The ChIP- sequencing analysis revealed that the PfCDP is majorly associated with clonally variant gene families, primarily rifins in P. falciparum. Conditional deletion of the chromodomain (CD) gene in P. falciparum leads to the up-regulation of a subset of virulence genes, including rifins, a few var, and stevor genes. Further, we show that PfΔCDP P. falciparum lines promote the RBC rosetting. This study provides evidence of an epigenetic regulator mediated control on a subset of RIFINs expression and RBC rosetting by P. falciparum.

scholarly journals Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Emanuel Schmid-Siegert ◽  
Sophie Richard ◽  
Amanda Luraschi ◽  
Konrad Mühlethaler ◽  
Marco Pagni ◽  
...  
Keyword(s):  
Immune System ◽  
Antigenic Variation ◽  
Continuous Production ◽  
Gene Families ◽  
Surface Proteins ◽  
Pneumocystis Jirovecii ◽  
Human Pathogens ◽  
Human Immune System ◽  
Life Threatening ◽  
Human Immune

ABSTRACT Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii. This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen from a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily, which included five families encoding adhesive glycosylphosphatidylinositol (GPI)-anchored glycoproteins and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins, which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favored by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i) the P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists of the continuous production of new subpopulations composed of cells that are antigenically different. IMPORTANCE Pneumocystis jirovecii is a fungus causing severe pneumonia in immunocompromised individuals. It is the second most frequent life-threatening invasive fungal infection. We have studied the mechanisms of antigenic variation used by this pathogen to escape the human immune system, a strategy commonly used by pathogenic microorganisms. Using a new DNA sequencing technology generating long reads, we could characterize the highly repetitive gene families encoding the proteins that are present on the cellular surface of this pest. These gene families are localized in the regions close to the ends of all chromosomes, the subtelomeres. Such chromosomal localization was found to favor genetic recombinations between members of each gene family and to allow diversification of these proteins continuously over time. This pathogen seems to use a strategy of antigenic variation consisting of the continuous production of new subpopulations composed of cells that are antigenically different. Such a strategy is unique among human pathogens. IMPORTANCE Pneumocystis jirovecii is a fungus causing severe pneumonia in immunocompromised individuals. It is the second most frequent life-threatening invasive fungal infection. We have studied the mechanisms of antigenic variation used by this pathogen to escape the human immune system, a strategy commonly used by pathogenic microorganisms. Using a new DNA sequencing technology generating long reads, we could characterize the highly repetitive gene families encoding the proteins that are present on the cellular surface of this pest. These gene families are localized in the regions close to the ends of all chromosomes, the subtelomeres. Such chromosomal localization was found to favor genetic recombinations between members of each gene family and to allow diversification of these proteins continuously over time. This pathogen seems to use a strategy of antigenic variation consisting of the continuous production of new subpopulations composed of cells that are antigenically different. Such a strategy is unique among human pathogens.

scholarly journals Helminth Glycans at the Host-Parasite Interface and Their Potential for Developing Novel Therapeutics

2022 ◽  
Vol 8 ◽  
Author(s):  
Myrna J. M. Bunte ◽  
Arjen Schots ◽  
Jan E. Kammenga ◽  
Ruud H. P. Wilbers
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Helminth Infection ◽  
Host Immune System ◽  
Lewis X ◽  
Novel Therapeutics ◽  
Antigenic Properties ◽  
Parasitic Worms ◽  
Host Parasite

Helminths are parasitic worms that have successfully co-evolved with their host immune system to sustain long-term infections. Their successful parasitism is mainly facilitated by modulation of the host immune system via the release of excretory-secretory (ES) products covered with glycan motifs such as Lewis X, fucosylated LDN, phosphorylcholine and tyvelose. Evidence is accumulating that these glycans play key roles in different aspects of helminth infection including interactions with immune cells for recognition and evasion of host defences. Moreover, antigenic properties of glycans can be exploited for improving the efficacy of anti-helminthic vaccines. Here, we illustrate that glycans have the potential to open new avenues for the development of novel biopharmaceuticals and effective vaccines based on helminth glycoproteins.

scholarly journals The Secretome of Filarial Nematodes and Its Role in Host-Parasite Interactions and Pathogenicity in Onchocerciasis-Associated Epilepsy

2021 ◽  
Vol 11 ◽  
Author(s):  
An Hotterbeekx ◽  
Jolien Perneel ◽  
Melissa Krizia Vieri ◽  
Robert Colebunders ◽  
Samir Kumar-Singh
Keyword(s):  
Immune System ◽  
Current Knowledge ◽  
Bioactive Molecules ◽  
Mammalian Host ◽  
Host Immune System ◽  
Pathogenic Potential ◽  
Host Parasite Interactions ◽  
Filarial Nematodes ◽  
Secretory Products ◽  
Host Parasite

Filarial nematodes secrete bioactive molecules which are of interest as potential mediators for manipulating host biology, as they are readily available at the host-parasite interface. The adult parasites can survive for years in the mammalian host, due to their successful modulation of the host immune system and most of these immunomodulatory strategies are based on soluble mediators excreted by the parasite. The secretome of filarial nematodes is a key player in both infection and pathology, making them an interesting target for further investigation. This review summarises the current knowledge regarding the components of the excretory-secretory products (ESPs) of filarial parasites and their bioactive functions in the human host. In addition, the pathogenic potential of the identified components, which are mostly proteins, in the pathophysiology of onchocerciasis-associated epilepsy is discussed.

scholarly journals Mutation and Recombination in the Upstream Homology Box-FlankedospE-Related Genes of the Lyme Disease Spirochetes Result in the Development of New Antigenic Variants during Infection

2000 ◽  
Vol 68 (3) ◽  
pp. 1319-1327 ◽  
Author(s):  
Shian Ying Sung ◽  
John V. McDowell ◽  
Jason A. Carlyon ◽  
Richard T. Marconi
Keyword(s):  
Immune System ◽  
Lyme Disease ◽  
Gene Family ◽  
Antigenic Variation ◽  
Gene Families ◽  
Upstream Sequence ◽  
Dna Repeats ◽  
Hydrophilic Surface ◽  
Related Proteins

ABSTRACT The ospE gene family of the Lyme disease spirochetes encodes a polymorphic group of immunogenic lipoproteins. The ospE genes are one of several gene families that are flanked by a highly conserved upstream sequence called the upstream homology box, or UHB, element. Earlier analyses in our lab demonstrated that ospE-related genes are characterized by defined hypervariable domains (domains 1 and 2) that are predicted to be hydrophilic, surface exposed, and antigenic. The flanking of hypervariable domain 1 by DNA repeats may indicate that recombination contributes to ospE diversity and thus ultimately to antigenic variation. Using an isogeneic clone of Borrelia burgdorferi B31G (designated B31Gc1), we demonstrate that theospE-related genes undergo mutation and rearrangement during infection in mice. The mutations that develop during infection resulted in the generation of OspE proteins with altered antigenic characteristics. The data support the hypothesized role of OspE-related proteins in immune system evasion.

scholarly journals Protective microbe enhances colonisation of a novel host species by modifying immune gene expression

2019 ◽  
Author(s):  
Suzanne A. Ford ◽  
Kayla C. King
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Immune Response ◽  
Immune System ◽  
Host Species ◽  
Gene Families ◽  
Host Immune Response ◽  
Host Immune System ◽  
Immune Gene ◽  
New Host

AbstractMicrobes that protect against infection inhabit hosts across the tree of life. It is unclear whether many protective microbes use or reduce the need for a host immune response, or how the immune system reacts when these microbes newly encounter a host species naturally and as part of a biocontrol strategy. We sequenced the transcriptome of a host (Caenorhabditis elegans) following its interaction with a non-native bacterium (Enterococcus faecalis) that has protective traits against the pathogen, Staphylococcus aureus. We show that microbe-mediated protection caused the differential expression of 1,557 genes, including the upregulation of many immune gene families conserved across the animal kingdom (e.g. lysozymes and c-type lectins). We found that this modulation of the host’s immune response was beneficial for both the protective microbe and the host. Given E. faecalis’ increased ability to resist lysozyme activity compared to S. aureus, our results indicate that the protective microbe could more easily invade and protect infected hosts by upregulating lysozyme genes. These results suggest that a protective microbe can exploit the host immune system even when introduced into a novel species. Microbes that protect via the host immune response in this way should favour continued investment into host immunity and avoid the evolution of host dependence.Author summaryOrganisms can be protected from infectious disease by the microbes they house. It is unclear, however, whether protective microbes affect the host immune response to infection, particularly in the early stages of symbiosis. In this study, we investigated the role of the host immune system in a novel protective interaction. We examined gene expression in a nematode after colonisation by a non-native microbe capable of suppressing the pathogen Staphylococcus aureus. The protective microbe altered the host immune response to infection in a way that it could exploit. By causing the host to increase the production of antimicrobials to which it itself is relatively resistant, the protective microbe was better able to colonise and defend infected hosts. These results indicate that protective microbes introduced into new host species can take advantage of the host immune system. Such a mechanism at the beginning of a protective symbiosis, formed either naturally or as part of a biocontrol strategy, could ensure continued investment in host-based defences over evolutionary time.

Role of Vasavaleha in the management of Covid19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 259-261
Author(s):  
Aamir Khan ◽  
Rajni K. Gurmule
Keyword(s):  
Immune System ◽  
Human Body ◽  
Respiratory Diseases ◽  
Spreading Rate ◽  
Host Immune System ◽  
Shortness Of Breath ◽  
Antitussive Effect ◽  
Corona Viruses ◽  
Very High

Vasavaleha is one of the best medicine given for respiratory diseases. Corona viruses typically affect the respiratory system, causing symptoms such as coughing, fever and shortness of breath. It also affects host immune system of human body. Spreading rate of this disease is very high. Whole world is seeking for the treatment which can uproots this diseases. There in no vaccine available till date against this pandemic disease. Ayurveda mainly focuses on prevention of diseases alongwith its total cure. Rajyakshma Vyadhi is MadhyamMarga Roga as per Ayurveda. It shows many symptoms such as Kasa, Shwasa etc. By overall view of Covid 19, shows its resemblance with Rajyakshma Vyadhi described in Ayurveda. Vasavaleha is a Kalpa which is described in Rogadhikara of Rajyakshma. It shows Kasahara, Shwashara properties. It consists of Vasa, Pipalli, Madhu and Goghrita. These components shows actions like bronchodilation, antitussive effect and many more other actions. Pipalli shows important Rasayana effect. So in present review, we have tried to focus on role of Vasavaleha in the management of Covid 19. This can be used as preventive as well as adjuvant medication in treating Covid 19. There is need of further clinical research to rule of exact action of Vasavaleha against Covid 19.

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