scholarly journals RibonucleaseH1-targeted R-loops in surface antigen gene expression sites can direct trypanosome immune evasion

2018 ◽  
Author(s):  
Emma Briggs ◽  
Kathryn Crouch ◽  
Leandro Lemgruber ◽  
Craig Lapsley ◽  
Richard McCulloch
Keyword(s):  
Immune Evasion ◽  
Protein Gene ◽  
Antigenic Variation ◽  
Surface Protein ◽  
Surface Glycoprotein ◽  
Surface Coat ◽  
Loop Formation ◽  
New Host ◽  
Genome Damage ◽  
Surface Protein Gene

AbstractSwitching of the Variant Surface Glycoprotein (VSG) inTrypanosoma bruceiprovides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions, each operating within specialised telomeric VSG expression sites (ES). VSG switching is likely triggered by events focused on the single actively transcribed ES, from a repertoire of around 15, but the nature of such events is unclear. Here we show that RNA-DNA hybrids, called R-loops, form preferentially within sequences termed the 70 bp repeats in the actively transcribed ES, but spread throughout the active and inactive ES in the absence of RNase H1, which degrades R-loops. Loss of RNase H1 also leads to increased levels of VSG coat switching and replication-associated genome damage, some of which accumulates within the active ES. This work indicates VSG ES architecture elicits R-loop formation, and that these RNA-DNA hybrids connectT. bruceiimmune evasion by transcription and recombination.Author summaryAll pathogens must survive eradication by the host immune response in order to continue infections and be passed on to a new host. Changes in the proteins expressed on the surface of the pathogen, or on the surface of the cells the pathogen infects, is a widely used strategy to escape immune elimination. Understanding how this survival strategy, termed antigenic variation, operates in any pathogen is critical, both to understand interaction between the pathogen and host and disease progression. A key event in antigenic variation is the initiation of the change in expression of the surface protein gene, though how this occurs has been detailed in very few pathogens. Here we examine how changes in expression of the surface coat of the African trypanosome, which causes sleeping sickness disease, are initiated. We reveal that specialised nucleic acid structures, termed R-loops, form around the expressed trypanosome surface protein gene and increase in abundance after mutation of an enzyme that removes them, leading to increased changes in the surface coat in trypanosome cells that are dividing. We therefore shed light on the earliest acting events in trypanosome antigenic variation.

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.

Reproducible and variable rearrangements of a Tetrahymena thermophila surface protein gene family occur during macronuclear development

1988 ◽  
Vol 8 (11) ◽  
pp. 5043-5046
Author(s):  
J P Kile ◽  
H D Love ◽  
C A Hubach ◽  
G A Bannon
Keyword(s):  
Environmental Regulation ◽  
Cdna Clone ◽  
Multigene Family ◽  
Protein Gene ◽  
Tetrahymena Thermophila ◽  
Surface Protein ◽  
Surface Proteins ◽  
Hybridization Probe ◽  
Macronuclear Development ◽  
Surface Protein Gene

The expression of Tetrahymena surface proteins serotype H3 (SerH3) and serotype T (SerT) is under environmental regulation. SerH3 is expressed when cells are incubated between the temperatures of 20 and 35 degrees C, while SerT is expressed when cells are grown at temperatures above 35 degrees C. Using a SerH3 cDNA clone as a hybridization probe, we determined that (i) the SerH3 gene is a member of a multigene family; (ii) most members of this multigene family are variably rearranged during macronuclear development; and (iii) the gene which produces the SerH3 mRNA is reproducibly rearranged during macronuclear development.

scholarly journals Antigenic diversity ofTheileriamajor piroplasm surface protein gene in Jeju black cattle

2008 ◽  
Vol 9 (2) ◽  
pp. 155 ◽  
Author(s):  
Myung-Soon Ko ◽  
Kyoung-Kap Lee ◽  
Kyu-Kye Hwang ◽  
Byung-Sun Kim ◽  
Gui-Cheol Choi ◽  
...  
Keyword(s):  
Protein Gene ◽  
Surface Protein ◽  
Antigenic Diversity ◽  
Surface Protein Gene ◽  
Jeju Black Cattle

scholarly journals Escaping the immune system by DNA repair and recombination in African trypanosomes

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190182 ◽  
Author(s):  
Núria Sima ◽  
Emilia Jane McLaughlin ◽  
Sebastian Hutchinson ◽  
Lucy Glover
Keyword(s):  
Immune Response ◽  
Dna Repair ◽  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Surface Coat ◽  
African Trypanosomes ◽  
Active Expression ◽  
Expression Site

African trypanosomes escape the mammalian immune response by antigenic variation—the periodic exchange of one surface coat protein, in Trypanosoma brucei the variant surface glycoprotein (VSG), for an immunologically distinct one. VSG transcription is monoallelic, with only one VSG being expressed at a time from a specialized locus, known as an expression site. VSG switching is a predominantly recombination-driven process that allows VSG sequences to be recombined into the active expression site either replacing the currently active VSG or generating a ‘new’ VSG by segmental gene conversion. In this review, we describe what is known about the factors that influence this process, focusing specifically on DNA repair and recombination.

scholarly journals Enterococcal Surface Protein Esp Is Important for Biofilm Formation of Enterococcus faecium E1162

2007 ◽  
Vol 189 (22) ◽  
pp. 8233-8240 ◽  
Author(s):  
Esther Heikens ◽  
Marc J. M. Bonten ◽  
Rob J. L. Willems
Keyword(s):  
Enterococcus Faecium ◽  
Biofilm Formation ◽  
Deletion Mutant ◽  
Wild Type Strain ◽  
Protein Gene ◽  
Surface Protein ◽  
Essential Factor ◽  
Wild Type ◽  
Surface Protein Gene ◽  
Multiple Antibiotics

ABSTRACT Enterococci have emerged as important nosocomial pathogens with resistance to multiple antibiotics. Adhesion to abiotic materials and biofilm formation on medical devices are considered important virulence properties. A single clonal lineage of Enterococcus faecium, complex 17 (CC17), appears to be a successful nosocomial pathogen, and most CC17 isolates harbor the enterococcal surface protein gene, esp. In this study, we constructed an esp insertion-deletion mutant in a clinical E. faecium CC17 isolate. In addition, initial adherence and biofilm assays were performed. Compared to the wild-type strain, the esp insertion-deletion mutant no longer produced Esp on the cell surface and had significantly lower initial adherence to polystyrene and significantly less biofilm formation, resulting in levels of biofilm comparable to those of an esp-negative isolate. Capacities for initial adherence and biofilm formation were restored in the insertion-deletion mutant by in trans complementation with esp. These results identify Esp as the first documented determinant in E. faecium CC17 with an important role in biofilm formation, which is an essential factor in infection pathogenesis.

scholarly journals PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector

2020 ◽  
Vol 117 (13) ◽  
pp. 7363-7373 ◽  
Author(s):  
Chiamaka V. Ukegbu ◽  
Maria Giorgalli ◽  
Sofia Tapanelli ◽  
Luisa D. P. Rona ◽  
Amie Jaye ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Immune Evasion ◽  
Malaria Parasite ◽  
Surface Protein ◽  
Innate Immune ◽  
Mosquito Vector ◽  
Anopheles Coluzzii ◽  
Innate Immune Responses ◽  
New Host ◽  
Mosquito Midgut

After being ingested by a female Anopheles mosquito during a bloodmeal on an infected host, and before they can reach the mosquito salivary glands to be transmitted to a new host, Plasmodium parasites must establish an infection of the mosquito midgut in the form of oocysts. To achieve this, they must first survive a series of robust innate immune responses that take place prior to, during, and immediately after ookinete traversal of the midgut epithelium. Understanding how parasites may evade these responses could highlight new ways to block malaria transmission. We show that an ookinete and sporozoite surface protein designated as PIMMS43 (Plasmodium Infection of the Mosquito Midgut Screen 43) is required for parasite evasion of the Anopheles coluzzii complement-like response. Disruption of PIMMS43 in the rodent malaria parasite Plasmodium berghei triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing components of the complement-like system through RNAi largely restores ookinete-to-oocyst transition but oocysts remain small in size and produce a very small number of sporozoites that additionally are not infectious, indicating that PIMMS43 is also essential for sporogonic development in the oocyst. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African Plasmodium falciparum populations indicates allelic adaptation to sympatric vector populations. These data add to our understanding of mosquito–parasite interactions and identify PIMMS43 as a target of malaria transmission blocking.

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