scholarly journals Segmental Variation in a Duplicatedmsp2Pseudogene GeneratesAnaplasma marginaleAntigenic Variants

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Telmo Graça ◽  
Pei-Shin Ku ◽  
Marta G. Silva ◽  
Joshua E. Turse ◽  
G. Kenitra Hammac ◽  
...  
Keyword(s):  
Persistent Infection ◽  
Immune Escape ◽  
Bacterial Pathogen ◽  
Surface Protein ◽  
Content Type ◽  
Full Complement ◽  
Expression Site ◽  
Segmental Variation ◽  
Major Surface ◽  
Sequential Generation

ABSTRACTAnaplasma marginaleis a prototypical highly antigenically variant bacterial pathogen dependent on the sequential generation of major surface protein 2 (Msp2) outer membrane variants to establish persistent infection. Msp2 is encoded by a single expression site, and diversity is achieved by gene conversion of chromosomally encodedmsp2pseudogenes. Analysis of the full complement ofmsp2pseudogenes in the St. Maries strain revealed identical sequences in different loci. The Florida strain shared the same locus structure, but in the loci where the St. Maries strain had two identical pseudogenes, the Florida strain had one whose sequence was identical to the St. Maries sequences, while the sequence of the second pseudogene differed. Consequently, we hypothesized that themsp2pseudogene repertoire arose via gene duplication, allowing structural variation to occur in one copy but the utility of the other to be retained. Using comparative genomics, we first established that duplication ofmsp2pseudogenes is common amongA. marginalestrains: all seven examined strains had at least one duplicate pair in which either the genes in the pair were maintained as identical copies or the genes contained segmental changes. We then demonstrated that a minimal segmental change in a duplicated pseudogene locus is sufficient for immune escape from the broad antibody response generated in a natural host, as is a completely divergent pseudogene sequence in an otherwise conserved locus. The results support a model in which a locus first duplicates, resulting in a second identical copy, and then progressively incorporates changes to generate anmsp2repertoire capable of generating sufficient antigenic variants to escape immunity and establish persistent infection.

scholarly journals Antigenic Variation of Anaplasma Marginale: Major Surface Protein 2 Diversity during Cyclic Transmission between Ticks and Cattle

2001 ◽  
Vol 69 (5) ◽  
pp. 3057-3066 ◽  
Author(s):  
A. F. Barbet ◽  
Jooyoung Yi ◽  
Anna Lundgren ◽  
B. R. McEwen ◽  
E. F. Blouin ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Salivary Glands ◽  
Antigenic Variation ◽  
Hypervariable Region ◽  
Surface Protein ◽  
Genomic Expression ◽  
Major Surface Protein ◽  
Expression Site ◽  
Major Surface ◽  
Tick Salivary Glands

ABSTRACT The rickettsial pathogen Anaplasma marginale expresses a variable immunodominant outer membrane protein, major surface protein 2 (MSP2), involved in antigenic variation and long-term persistence of the organism in carrier animals. MSP2 contains a central hypervariable region of about 100 amino acids that encodes immunogenic B-cell epitopes that induce variant-specific antibodies during infection. Previously, we have shown that MSP2 is encoded on a polycistronic mRNA transcript in erythrocyte stages of A. marginale and defined the structure of the genomic expression site for this transcript. In this study, we show that the same expression site is utilized in stages of A. marginale infecting tick salivary glands. We also analyzed the variability of this genomic expression site in Oklahoma strain A. marginale transmitted from in vitro cultures to cattle and between cattle and ticks. The structure of the expression site and flanking regions was conserved except for sequence that encoded the MSP2 hypervariable region. At least three different MSP2 variants were encoded in each A. marginalepopulation. The major sequence variants did not change on passage ofA. marginale between culture, acute erythrocyte stage infections, and tick salivary glands but did change during persistent infections of cattle. The variant types found in tick salivary glands most closely resembled those present in bovine blood at the time of acquisition of infection, whether infection was acquired from an acute or from a persistent rickettsemia. These variations in structure of an expression site for a major, immunoprotective outer membrane protein have important implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.

scholarly journals The polymorphic telomeres of the African trypanosome Trypanosoma brucei

2000 ◽  
Vol 28 (5) ◽  
pp. 536-540 ◽  
Author(s):  
G. Rudenko
Keyword(s):  
Trypanosoma Brucei ◽  
Surface Protein ◽  
Bloodstream Form ◽  
African Trypanosomes ◽  
African Trypanosome ◽  
Major Surface Protein ◽  
Genes Encoding ◽  
Expression Site ◽  
Major Surface

African trypanosomes have plastic genomes with extensive variability at the chromosome ends. The genes encoding the expressed major surface protein of the infective bloodstream form stages of Trypanosoma brucei and are located at telomeres. These telomeric expression-site transcription units are turning out to be surprisingly polymorphic in structure and sequence.

scholarly journals Surface Protein Variation by Expression Site Switching in the Relapsing Fever Agent Borrelia hermsii

2000 ◽  
Vol 68 (12) ◽  
pp. 7114-7121 ◽  
Author(s):  
Alan G. Barbour ◽  
Carol J. Carter ◽  
Charles D. Sohaskey
Keyword(s):  
Membrane Protein ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Relapsing Fever ◽  
Borrelia Hermsii ◽  
Immunodeficient Mice ◽  
Major Surface Protein ◽  
Protein Variation ◽  
Expression Site ◽  
Major Surface

ABSTRACT Borrelia hermsii, an agent of relapsing fever, undergoes antigenic variation of serotype-specifying membrane proteins during mammalian infections. When B. hermsii is cultivated in broth medium, one serotype, 33, eventually predominates in the population. Serotype 33 has also been found to be dominant in ticks but not in mammalian hosts. We investigated the biology and genetics of two independently derived clonal populations of serotype 33 of B. hermsii. Both isolates infected immunodeficient mice, but serotype 33 cells were limited in number and were only transiently present in the blood. Probes for vsp33, which encodes the serotype-specifying Vsp33 outer membrane protein, revealed that the gene was located on a 53-kb linear plasmid and that there was only one locus for the gene in serotype 33. The vsp33 probe and probes for other variable membrane protein genes showed that expression of Vsp33 was determined at the level of transcription and that when thevsp33 expression site was active, an expression site for other variable proteins was silent. The study confirmed that serotype 33 is distinct from other serotypes of B. hermsii in its biology and demonstrated that B. hermsii can change its major surface protein through switching between two expression sites.

scholarly journals Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

2016 ◽  
Vol 84 (6) ◽  
pp. 1693-1703 ◽  
Author(s):  
Christopher J. Greene ◽  
Laura R. Marks ◽  
John C. Hu ◽  
Ryan Reddinger ◽  
Lorrie Mandell ◽  
...  
Keyword(s):  
Influenza A ◽  
Pneumococcal Disease ◽  
Protein A ◽  
Surface Protein ◽  
Attractive Alternative ◽  
Long Term Effects ◽  
Content Type ◽  
Vaccine Type ◽  
Novel Strategy ◽  
Major Surface

Streptococcus pneumoniaecommonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensalS. pneumoniaeto disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g.,Streptococcus pyogenes,Staphylococcus aureus, and potentiallyHaemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.

scholarly journals The Antibacterial Activity of LL-37 against Treponema denticola Is Dentilisin Protease Independent and Facilitated by the Major Outer Sheath Protein Virulence Factor

2011 ◽  
Vol 80 (3) ◽  
pp. 1107-1114 ◽  
Author(s):  
Graciela Rosen ◽  
Michael N. Sela ◽  
Gilad Bachrach
Keyword(s):  
Periodontal Disease ◽  
Host Defense ◽  
Surface Protein ◽  
Human Saliva ◽  
Treponema Denticola ◽  
Host Defense Peptides ◽  
Content Type ◽  
Outer Sheath ◽  
Major Surface

Host defense peptides are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. Deficiency in the human host defense peptide LL-37 has previously been correlated with severe periodontal disease.Treponema denticolais an oral anaerobic spirochete closely associated with the pathogenesis of periodontal disease. TheT. denticolamajor surface protein (MSP), involved in adhesion and cytotoxicity, and the dentilisin serine protease are key virulence factors of this organism. In this study, we examined the interactions between LL-37 andT. denticola. The threeT. denticolastrains tested were susceptible to LL-37. Dentilisin was found to inactivate LL-37 by cleaving it at the Lys, Phe, Gln, and Val residues. However, dentilisin deletion did not increase the susceptibility ofT. denticolato LL-37. Furthermore, dentilisin activity was found to be inhibited by human saliva. In contrast, a deficiency of theT. denticolaMSP increased resistance to LL-37. The MSP-deficient mutant bound less fluorescently labeled LL-37 than the wild-type strain. MSP demonstrated specific, dose-dependent LL-37 binding. In conclusion, though capable of LL-37 inactivation, dentilisin does not protectT. denticolafrom LL-37. Rather, the rapid, MSP-mediated binding of LL-37 to the treponemal outer sheath precedes cleavage by dentilisin. Moreover,in vivo, saliva inhibits dentilisin, thus preventing LL-37 restriction and ensuring its bactericidal and immunoregulatory activities.

scholarly journals Expression and Immunogenicity of Recombinant Immunoreactive Surface Protein 2 of Anaplasma phagocytophilum

2012 ◽  
Vol 19 (6) ◽  
pp. 919-923 ◽  
Author(s):  
Qiang Yu ◽  
Chuang-fu Chen ◽  
Qiang Chen ◽  
Li-juan Zhang
Keyword(s):  
Recombinant Protein ◽  
Anaplasma Phagocytophilum ◽  
Surface Protein ◽  
Immunofluorescence Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Major Surface Protein ◽  
Granulocytic Anaplasmosis ◽  
Major Surface ◽  
Diagnostic Reagent

ABSTRACTHuman granulocytic anaplasmosis (HGA), caused byAnaplasma phagocytophilum, is an emerging tick-borne zoonotic disease throughout the world. The first HGA cases in China were documented in 2008, and the greatest challenge posed by the disease is rapid and accurate diagnosis during the acute phage of illness. In this study, we successfully cloned and expressed anA. phagocytophilumimmunoreactive surface protein (major surface protein 2 [MSP2]) and demonstrated that this recombinant protein has natural immunogenicity by Western blotting and enzyme-linked immunosorbent assay (ELISA) using human HGA-positive sera and reference rabbit HGA-positive sera. The rabbit antisera against the recombinant protein also reacted actively with the natural antigen ofA. phagocytophilumby immunofluorescence assay (IFA). No cross-reaction was observed between the recombinant protein and rabbit antisera against 10 common members of the orderRickettsialesby ELISA when the sera were diluted more than 1:100. We concluded that the recombinant MSP2 protein exhibited excellent antigenicity and specificity, results that should lay the foundation for the development of a simple and rapid diagnostic reagent and a vaccination for anaplasmosis.

scholarly journals Diversity and complexity of the large surface protein family in the compacted genomes of various Pneumocystis species

2019 ◽  
Author(s):  
Liang Ma ◽  
Zehua Chen ◽  
Da Wei Huang ◽  
Ousmane H. Cissé ◽  
Jamie L. Rothenburger ◽  
...  
Keyword(s):  
Antigenic Variation ◽  
Life Stage ◽  
Surface Protein ◽  
Opportunistic Pathogen ◽  
Surface Proteins ◽  
Surface Glycoprotein ◽  
Mammalian Host ◽  
Expression Site ◽  
Phylogeny And Evolution ◽  
Major Surface

AbstractPneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multi-copy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins, and provide detailed description of the classification, unique characteristics and phylogenetic relatedness of five Msg families. We further describe the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests a wide variety of functions for this superfamily, not only conferring antigenic variation to allow immune evasion but also mediating life-stage development, optimizing cell mobility and adhesion, and adapting to specific host niches or environmental conditions. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.

scholarly journals Hide and seek: interplay between influenza viruses and B cells

2020 ◽  
Vol 32 (9) ◽  
pp. 605-611 ◽  
Author(s):  
Masayuki Kuraoka ◽  
Yu Adachi ◽  
Yoshimasa Takahashi
Keyword(s):  
B Cells ◽  
B Cell ◽  
Surface Protein ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Native Structure ◽  
Humoral Immune ◽  
Protective Antibodies ◽  
Major Surface ◽  
And Function

Abstract Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

Three strains of Wolbachia pipientis and high rates of infection in Iranian sandfly species

2014 ◽  
Vol 104 (2) ◽  
pp. 195-202 ◽  
Author(s):  
A. Bordbar ◽  
S. Soleimani ◽  
F. Fardid ◽  
M.R. Zolfaghari ◽  
P. Parvizi
Keyword(s):  
Protein Gene ◽  
Surface Protein ◽  
Male And Female ◽  
Wolbachia Pipientis ◽  
Major Surface Protein ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Geographical Regions ◽  
Surface Protein Gene ◽  
Major Surface ◽  
Zoonotic Visceral Leishmaniasis

AbstractIndividual wild-caught sandflies from Iran were examined for infections of Wolbachia pipientis by targeting the major surface protein gene wsp of this intracellular α-proteobacterium. In total, 638 male and female sandflies were screened, of which 241 were found to be positive for one of three wsp haplotypes. Regardless of geographical origins and habitats, Phlebotomus (Phlebotomus) papatasi and other sandfly species were found to be infected with one common, widespread strain of A-group W. pipientis (Turk 54, GenBank accession EU780683; AY288297). In addition, a new A-group haplotype (Turk07, GenBank accession KC576916) was isolated from Phlebotomus (Paraphlebotomus) mongolensis and Phlebotomus (Pa.) caucasicus, and a new B-group haplotype (AZ2331, GenBank accession JX488735) was isolated from Phlebotomus (Larroussius) perfiliewi. Therefore, Wolbachia was found to occur in at least three of the incriminated vectors of zoonotic cutaneous leishmaniasis and zoonotic visceral leishmaniasis in different geographical regions of Iran. It may provide a new tool for the future control of leishmaniasis.

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