Developmental competence and antigen switch frequency can be uncoupled in Trypanosoma brucei
| Autor: | Monica R. Mugnier, Liam J. Morrison, Kirsty R. McWilliam, Keith R. Matthews, Alasdair Ivens |
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| Rok vydání: | 2019 |
| Předmět: |
Trypanosoma
Trypanosoma brucei brucei Antigens Protozoan antigenic variation Trypanosoma brucei Microbiology 03 medical and health sciences Antigen Serial passage Antigenic variation Animals Gene silencing Parasite hosting immune evasion 030304 developmental biology Genetics 0303 health sciences Multidisciplinary biology 030306 microbiology differentiation Biological Sciences biology.organism_classification Quorum sensing parasite RNA Interference Variant Surface Glycoproteins Trypanosoma |
| Zdroj: | McWilliam, K, Ivens, A, Morrison, L, Mugnier, M & Matthews, K 2019, ' Developmental competence and antigen switch frequency can be uncoupled in Trypanosoma brucei ', Proceedings of the National Academy of Sciences, vol. 116, no. 45, pp. 22774-22782 . https://doi.org/10.1073/pnas.1912711116 Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1912711116 |
| Popis: | Significance Trypanosomes are blood-borne protozoa that cause human sleeping sickness and the livestock disease, nagana. These extracellular parasites sustain infection through their ability to change their surface proteins, a process called antigenic variation. They also promote their own transmission by development in the bloodstream to so-called “stumpy forms” generated in response to parasite density. Earlier studies have proposed that reduced capacity for stumpy formation also generates reduced antigen switch frequency, suggesting these processes are mechanistically coupled. Here, by silencing the density-sensing pathway or selecting parasites less able to generate stumpy forms, we demonstrate that these processes are under independent selection. This has relevance for parasite virulence, spread, and competition and for the selection of trypanosome species directly transmitted by biting flies. 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. |
| Databáze: | OpenAIRE |
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