Antigenic Variation in the Salivarian Trypanosomes

ABSTRACT Gene diversification is a common mechanism pathogens use to alter surface structures to aid in immune avoidance. Neisseria gonorrhoeae uses a gene conversion-based diversification system to alter the primary sequence of the gene encoding the major subunit of the pilus, pilE. Antigenic variation occurs when one of the nonexpressed 19 silent copies donates part of its DNA sequence to pilE. We have developed a method using Pacific Biosciences (PacBio) amplicon sequencing and custom software to determine pilin antigenic variation frequencies. The program analyzes 37 variable regions across the strain FA1090 1-81-S2 pilE gene and can be modified to determine sequence variation from other starting pilE sequences or other diversity generation systems. Using this method, we measured pilin antigenic variation frequencies for various derivatives of strain FA1090 and showed we can also analyze pilin antigenic variation frequencies during macrophage infection. IMPORTANCE Diversity generation systems are used by many unicellular organism to provide subpopulations of cell with different properties that are available when needed. We have developed a method using the PacBio DNA sequencing technology and a custom computer program to analyze the pilin antigenic variation system of the organism that is the sole cause of the sexually transmitted infection, gonorrhea.

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Developmental competence and antigen switch frequency can be uncoupled in Trypanosoma brucei

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1912711116 ◽

2019 ◽

Vol 116 (45) ◽

pp. 22774-22782 ◽

Cited By ~ 1

Author(s):

Kirsty R. McWilliam ◽

Alasdair Ivens ◽

Liam J. Morrison ◽

Monica R. Mugnier ◽

Keith R. Matthews

Keyword(s):

Trypanosoma Brucei ◽

Antigenic Variation ◽

Experimental Studies ◽

Developmental Competence ◽

Parasite Development ◽

Mammalian Host ◽

Mechanical Transmission ◽

African Trypanosomes ◽

Infection Dynamic ◽

Developmental Capacity

African trypanosomes use an extreme form of antigenic variation to evade host immunity, involving the switching of expressed variant surface glycoproteins by a stochastic and parasite-intrinsic process. Parasite development in the mammalian host is another feature of the infection dynamic, with trypanosomes undergoing quorum sensing (QS)-dependent differentiation between proliferative slender forms and arrested, transmissible, stumpy forms. Longstanding experimental studies have suggested that the frequency of antigenic variation and transmissibility may be linked, antigen switching being higher in developmentally competent, fly-transmissible, parasites (“pleomorphs”) than in serially passaged “monomorphic” lines that cannot transmit through flies. Here, we have directly tested this tenet of the infection dynamic by using 2 experimental systems to reduce pleomorphism. Firstly, lines were generated that inducibly lose developmental capacity through RNAi-mediated silencing of the QS signaling machinery (“inducible monomorphs”). Secondly, de novo lines were derived that have lost the capacity for stumpy formation by serial passage (“selected monomorphs”) and analyzed for their antigenic variation in comparison to isogenic preselected populations. Analysis of both inducible and selected monomorphs has established that antigen switch frequency and developmental capacity are independently selected traits. This generates the potential for diverse infection dynamics in different parasite populations where the rate of antigenic switching and transmission competence are uncoupled. Further, this may support the evolution, maintenance, and spread of important trypanosome variants such as Trypanosoma brucei evansi that exploit mechanical transmission.

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Transferrin receptor, antigenic variation and the prospect of a trypanosome vaccine

Trends in Genetics ◽

10.1016/0168-9525(91)90406-g ◽

1991 ◽

Vol 7 (10) ◽

pp. 307-309 ◽

Cited By ~ 15

Author(s):

P. Borst

Keyword(s):

Transferrin Receptor ◽

Antigenic Variation

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Targeting the Variable Surface of African Trypanosomes with Variant Surface Glycoprotein-Specific, Serum-Stable RNA Aptamers

Eukaryotic Cell ◽

10.1128/ec.2.1.84-94.2003 ◽

2003 ◽

Vol 2 (1) ◽

pp. 84-94 ◽

Cited By ~ 55

Author(s):

Mihaela Lorger ◽

Markus Engstler ◽

Matthias Homann ◽

H. Ulrich Göringer

Keyword(s):

Antigenic Variation ◽

Sleeping Sickness ◽

Rna Aptamers ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Parasite Protein ◽

African Trypanosomes ◽

Variable Surface ◽

New Strategy

ABSTRACT African trypanosomes cause sleeping sickness in humans and Nagana in cattle. The parasites multiply in the blood and escape the immune response of the infected host by antigenic variation. Antigenic variation is characterized by a periodic change of the parasite protein surface, which consists of a variant glycoprotein known as variant surface glycoprotein (VSG). Using a SELEX (systematic evolution of ligands by exponential enrichment) approach, we report the selection of small, serum-stable RNAs, so-called aptamers, that bind to VSGs with subnanomolar affinity. The RNAs are able to recognize different VSG variants and bind to the surface of live trypanosomes. Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness.

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The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of plasmodium falciparum-infected erythrocytes

Cell ◽

10.1016/0092-8674(95)90055-1 ◽

1995 ◽

Vol 82 (1) ◽

pp. 89-100 ◽

Cited By ~ 802

Author(s):

Xin-zhuan Su ◽

Virginia M. Heatwole ◽

Samuel P. Wertheimer ◽

Frangoise Guinet ◽

Jacqueline A. Herrfeldt ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Gene Family ◽

Antigenic Variation

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