Developmental regulation and extracellular release of a VSG expression-site-associated gene product from Trypanosoma brucei bloodstream forms.
Trypanosomes evade host immunity by exchanging variant surface glycoprotein (VSG) coats. VSG genes are transcribed from telomeric expression sites, which contain a diverse family of expression-site-associated genes (ESAGs). We have discovered that the mRNAs for one ESAG family, ESAG9, are strongly developmentally regulated, being enriched in stumpy forms, a life-cycle stage in the mammalian bloodstream that is important for the maintenance of chronic parasite infections and for tsetse transmission. ESAG9 gene sequences are highly diverse in the genome and encode proteins with weak similarity to the massively diverse MASP proteins in Trypanosoma cruzi. We demonstrate that ESAG9 proteins are modified by N-glycosylation and can be shed to the external milieu, this being dependent upon coexpression with at least one other family member. The expression profile and extracellular release of ESAG9 proteins represents a novel and unexpected aspect of the transmission biology of trypanosomes in their mammalian host. We suggest that these molecules might interact with the external environment, with possible implications for infection chronicity or parasite transmission.
Barnwell
Eleanor M
EM
Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, Kings' Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
van Deursen
Frederick J
FJ
Jeacock
Laura
L
Smith
Katherine A
KA
Maizels
Rick M
RM
Acosta-Serrano
Alvaro
A
Matthews
Keith
K
D000818:Animals; D017848:Blood-Borne Pathogens / Q000302:isolation & purification; D002460:Cell Line; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006031:Glycosylation; D008018:Life Cycle Stages / Q000235:genetics; D051379:Mice; D015202:Protein Engineering; D019076:Transgenes / Q000235:genetics; D014346:Trypanosoma brucei brucei / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D014353:Trypanosomiasis, African / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000635:transmission; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000096:biosynthesis* / Q000235:genetics; D014774:Virulence
D014643:Variant Surface Glycoproteins, Trypanosoma
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