Expression Pattern of the Pneumocystis jirovecii Major Surface Glycoprotein Superfamily in Patients with Pneumonia

Abstract Background The human pathogen Pneumocystis jirovecii harbors 6 families of major surface glycoproteins (MSGs) encoded by a single gene superfamily. MSGs are presumably responsible for antigenic variation and adhesion to host cells. The genomic organization suggests that a single member of family I is expressed at a given time per cell, whereas members of the other families are simultaneously expressed. Methods We analyzed RNA sequences expressed in several clinical samples, using specific weighted profiles for sorting of reads and calling of single-nucleotide variants to estimate the diversity of the expressed genes. Results A number of different isoforms of at least 4 MSG families were expressed simultaneously, including isoforms of family I, for which confirmation was obtained in the wet laboratory. Conclusion These observations suggest that every single P. jirovecii population is made of individual cells with distinct surface properties. Our results enhance our understanding of the unique antigenic variation system and cell surface structure of P. jirovecii.

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Anaplasma marginale(Rickettsiales: Anaplasmataceae): recent advances in defining host–pathogen adaptations of a tick-borne rickettsia

Parasitology ◽

10.1017/s0031182003004700 ◽

2004 ◽

Vol 129 (S1) ◽

pp. S285-S300 ◽

Cited By ~ 161

Author(s):

K. M. KOCAN ◽

J. DE LA FUENTE ◽

E. F. BLOUIN ◽

J. C. GARCIA-GARCIA

Keyword(s):

Antigenic Variation ◽

Control Strategies ◽

Anaplasma Marginale ◽

Surface Proteins ◽

Host Cells ◽

Developmental Cycle ◽

Persistent Infections ◽

Phylogenetic Studies ◽

Major Surface Proteins ◽

Major Surface

The tick-borne intracellular pathogenAnaplasma marginale(Rickettsiales: Anaplasmataceae) develops persistent infections in cattle and tick hosts. While erythrocytes appear to be the only site of infection in cattle,A. marginaleundergoes a complex developmental cycle in ticks and transmission occurs via salivary glands during feeding. Many geographic isolates occur that vary in genotype, antigenic composition, morphology and infectivity for ticks. In this chapter we review recent research on the host–vector–pathogen interactions ofA. marginale. Major surface proteins (MSPs) play a crucial role in the interaction ofA. marginalewith host cells. The MSP1a protein, which is an adhesin for bovine erythrocytes and tick cells, is differentially regulated and affects infection and transmission ofA. marginalebyDermacentorspp. ticks. MSP2 undergoes antigenic variation and selection in cattle and ticks, and contributes to the maintenance of persistent infections. Phylogenetic studies ofA. marginalegeographic isolates usingmsp4andmsp1α provide information about the biogeography and evolution ofA. marginale:msp1α genotypes evolve under positive selection pressure. Isolates ofA. marginaleare maintained by independent transmission events and a mechanism of infection exclusion in cattle and ticks allows for only the infection of one isolate per animal. Prospects for development of control strategies by use of pathogen and tick-derived antigens are discussed. TheA. marginale/vector/host studies described herein could serve as a model for research on other tick-borne rickettsiae.

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The Fungal PCR Initiative's evaluation of in-house and commercial Pneumocystis jirovecii qPCR assays: Toward a standard for a diagnostics assay

Medical Mycology ◽

10.1093/mmy/myz115 ◽

2019 ◽

Vol 58 (6) ◽

pp. 779-788 ◽

Cited By ~ 8

Author(s):

Maud Gits-Muselli ◽

P Lewis White ◽

Carlo Mengoli ◽

Sharon Chen ◽

Brendan Crowley ◽

...

Keyword(s):

Target Genes ◽

Clinical Care ◽

Large Subunit ◽

Reference Method ◽

Pneumocystis Pneumonia ◽

Surface Glycoprotein ◽

Pneumocystis Jirovecii ◽

Tubulin Genes ◽

Major Surface Glycoprotein ◽

Major Surface

Abstract Quantitative real-time PCR (qPCR) is increasingly used to detect Pneumocystis jirovecii for the diagnosis of Pneumocystis pneumonia (PCP), but there are differences in the nucleic acids targeted, DNA only versus whole nucleic acid (WNA), and also the target genes for amplification. Through the Fungal PCR Initiative, a working group of the International Society for Human and Animal Mycology, a multicenter and monocenter evaluation of PCP qPCR assays was performed. For the multicenter study, 16 reference laboratories from eight different countries, performing 20 assays analyzed a panel consisting of two negative and three PCP positive samples. Aliquots were prepared by pooling residual material from 20 negative or positive- P. jirovecii bronchoalveolar lavage fluids (BALFs). The positive pool was diluted to obtain three concentrations (pure 1:1; 1:100; and 1:1000 to mimic high, medium, and low fungal loads, respectively). The monocenter study compared five in-house and five commercial qPCR assays testing 19 individual BALFs on the same amplification platform. Across both evaluations and for all fungal loads, targeting WNA and the mitochondrial small sub-unit (mtSSU) provided the earliest Cq values, compared to only targeting DNA and the mitochondrial large subunit, the major surface glycoprotein or the beta-tubulin genes. Thus, reverse transcriptase-qPCR targeting the mtSSU gene could serve as a basis for standardizing the P. jirovecii load, which is essential if qPCR is to be incorporated into clinical care pathways as the reference method, accepting that additional parameters such as amplification platforms still need evaluation.

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Genetics of Surface Antigen Expression inPneumocystis carinii

Infection and Immunity ◽

10.1128/iai.69.2.627-639.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 627-639 ◽

Cited By ~ 72

Author(s):

James R. Stringer ◽

Scott P. Keely

Keyword(s):

Antigenic Variation ◽

Molecular Genetic ◽

Pneumocystis Carinii ◽

Antigen Expression ◽

Surface Glycoprotein ◽

Major Surface Glycoprotein ◽

Molecular Genetic Data ◽

Surface Variation ◽

Surface Antigen Expression ◽

Major Surface

ABSTRACT This article reviews the molecular genetic data pertaining to the major surface glycoprotein (MSG) gene family of Pneumocystis carinii and its role in surface variation and compares this fungal system to antigenic variation systems in the protozoanTrypanosoma brucei and the bacteriaBorrelia spp.

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Ode to Oseltamivir and Amantadine?

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2006/106989 ◽

2006 ◽

Vol 17 (1) ◽

pp. 11-14 ◽

Cited By ~ 5

Author(s):

JM Conly ◽

BL Johnston

Keyword(s):

Influenza A ◽

Antigenic Variation ◽

Interleukin 1 ◽

Influenza Viruses ◽

Host Cells ◽

Surface Glycoprotein ◽

Influenza B ◽

Influenza A Viruses ◽

Epidemic Disease ◽

Specific Antigens

Influenza A and B viruses are the two major types of influenza viruses that cause human epidemic disease. Influenza A viruses are further categorized into subtypes based on two surface antigens: hemagglutinin (H) and neuraminidase (N). Influenza B viruses are not categorized into subtypes (1). Influenza A viruses are found in many animal species, including humans, ducks, chickens, pigs, whales, horses and seals, whereas influenza B viruses circulate only among humans. The H antigen contains common and strain-specific antigens, demonstrates antigenic variation, and acts as a site of attachment of the virus to host cells to initiate infection (1). The N antigen contains subtype-specific antigens and also demonstrates antigenic variation between subtypes. It is a surface glycoprotein possessing enzymatic activity essential for viral replication in both influenza A and B viruses. The N antigen allows the release of newly produced virions from infected host cells, prevents the formation of viral aggregates after release from the host cells, and prevents viral inactivation by respiratory mucous (2,3). It is thought that this enzyme may also promote viral penetration into respiratory epithelial cells and may contribute to the pathogenicity of the virus by promoting production of proinflammatory cytokines such as interleukin-1 and tumour necrosis factor from macrophages (4-6).

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Regulation of Antigenic Variation by Trypanosoma brucei Telomere Proteins Depends on Their Unique DNA Binding Activities

Pathogens ◽

10.3390/pathogens10080967 ◽

2021 ◽

Vol 10 (8) ◽

pp. 967

Author(s):

Bibo Li ◽

Yanxiang Zhao

Keyword(s):

Nucleic Acid ◽

Trypanosoma Brucei ◽

Antigenic Variation ◽

Dna Recombination ◽

Surface Glycoprotein ◽

Monoallelic Expression ◽

Nucleic Acid Binding ◽

Major Surface ◽

Telomere Structure

Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, Variant Surface Glycoprotein (VSG), to evade the host immune response. Such antigenic variation is a key pathogenesis mechanism that enables T. brucei to establish long-term infections. VSG is expressed exclusively from subtelomere loci in a strictly monoallelic manner, and DNA recombination is an important VSG switching pathway. The integrity of telomere and subtelomere structure, maintained by multiple telomere proteins, is essential for T. brucei viability and for regulating the monoallelic VSG expression and VSG switching. Here we will focus on T. brucei TRF and RAP1, two telomere proteins with unique nucleic acid binding activities, and summarize their functions in telomere integrity and stability, VSG switching, and monoallelic VSG expression. Targeting the unique features of TbTRF and TbRAP1′s nucleic acid binding activities to perturb the integrity of telomere structure and disrupt VSG monoallelic expression may serve as potential therapeutic strategy against T. brucei.

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Trypanosoma brucei Interaction with Host: Mechanism of VSG Release as Target for Drug Discovery for African Trypanosomiasis

International Journal of Molecular Sciences ◽

10.3390/ijms20061484 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1484 ◽

Cited By ~ 1

Author(s):

Cláudia Moreno ◽

Adriana Temporão ◽

Taffarel Torres ◽

Marcelo Sousa Silva

Keyword(s):

Drug Discovery ◽

Phospholipase C ◽

Trypanosoma Brucei ◽

Antigenic Variation ◽

Surface Glycoprotein ◽

Mammalian Host ◽

African Trypanosomiasis ◽

Variable Surface Glycoprotein ◽

Variable Surface ◽

Major Surface

The protozoan Trypanosoma brucei, responsible for animal and human trypanosomiasis, has a family of major surface proteases (MSPs) and phospholipase-C (PLC), both involved in some mechanisms of virulence during mammalian infections. During parasitism in the mammalian host, this protozoan is exclusively extracellular and presents a robust mechanism of antigenic variation that allows the persistence of infection. There has been incredible progress in our understanding of how variable surface glycoproteins (VSGs) are organised and expressed, and how expression is switched, particularly through recombination. The objective of this manuscript is to create a reflection about the mechanisms of antigenic variation in T. brucei, more specifically, in the process of variable surface glycoprotein (VSG) release. We firstly explore the mechanism of VSG release as a potential pathway and target for the development of anti-T. brucei drugs.

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Use of Oropharyngeal Washes to Diagnose and Genotype Pneumocystis jirovecii

Open Forum Infectious Diseases ◽

10.1093/ofid/ofv080 ◽

2015 ◽

Vol 2 (3) ◽

Cited By ~ 5

Author(s):

Jonathan J. Juliano ◽

Eric Barnett ◽

Christian M. Parobek ◽

Steve M. Taylor ◽

Steven R. Meshnick ◽

...

Keyword(s):

Clinical Symptoms ◽

High Sensitivity ◽

Diagnostic Techniques ◽

Surface Glycoprotein ◽

Pneumocystis Jirovecii ◽

Major Surface Glycoprotein ◽

Immunodeficiency Virus ◽

Noninvasive Samples ◽

Strain Type ◽

Major Surface

Abstract Pneumocystis jirovecii is a symbiotic respiratory fungus that presents in 2 clinical forms: pneumonia in immunocompromised patients or colonization, defined by the presence of the organism without associated clinical symptoms. Currently, diagnosis requires invasive bronchoscopy, which may not be available in some settings and is inappropriate for detecting colonization in healthy individuals. Noninvasive diagnostic techniques and molecular strain typing tools that can be used on these samples are critical for conducting studies to better understand transmission. We evaluated 2 real-time polymerase chain reaction (PCR) assays targeting dihydropteroate synthase and the major surface glycoprotein for detection in 77 oropharyngeal washes (OPWs) from 43 symptomatic human immunodeficiency virus-infected patients who underwent bronchoscopy. We also evaluated the ability of a new microsatellite (MS) genotyping panel to strain type infections from these samples. Each PCR used individually provided a high sensitivity (>80%) for detection of pneumonia but a modest specificity (<70%). When used in combination, specificity was increased to 100% with a drop in sensitivity (74%). Concentration of organisms by PCR in the OPW tended to be lower in colonized individuals compared with those with pneumonia, but differences in concentration could not clearly define colonization in symptomatic individuals. Oropharyngeal wash samples were genotyped using 6 MSs with ≥4 alleles successfully genotyped in the majority of colonized patients and ≥5 alleles in patients with pneumonia. The MS profile was consistent over time within patients with serial OPWs analyzed. Microsatellite genotyping on noninvasive samples may aid in studying the molecular epidemiology of this pathogen without requiring invasive diagnostic techniques.

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Immunodominant surface epitopes power immune evasion in the African trypanosome

10.1101/2021.07.20.453071 ◽

2021 ◽

Author(s):

Anastasia Gkeka ◽

Francisco Aresta-Branco ◽

Gianna Triller ◽

Evi P Vlachou ◽

Mirjana Lilic ◽

...

Keyword(s):

Immune Evasion ◽

Antigenic Variation ◽

Cross Reactivity ◽

Surface Glycoprotein ◽

Mammalian Host ◽

African Trypanosome ◽

Repetitive Nature ◽

Variable Surface ◽

Major Surface ◽

Immunodominant Epitopes

The African trypanosome survives the immune response of its mammalian host by antigenic variation of its major surface antigen (the Variable Surface Glycoprotein, or VSG). Here we describe the antibody repertoires elicited by different VSGs. We show that the repertoires are highly restricted, directed predominantly to epitopes on the surface of the VSGs. They are also highly discriminatory: minor alterations within these exposed epitopes confer antigenically-distinct properties to these VSGs and elicit different repertoires. We propose that the patterned and repetitive nature of the VSG coat focuses host immunity to a restricted set of immunodominant epitopes per VSG, eliciting a highly stereotyped response, minimizing cross reactivity between different VSGs and facilitating prolonged immune evasion through epitope variation.

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