The Trypanosoma brucei MISP family of invariant proteins is co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector

Casas Sanchez, Aitor ORCID: https://orcid.org/0000-0001-5237-1223, Ramaswamy, Raghavendran, Perally, Samirah, Haines, Lee ORCID: https://orcid.org/0000-0001-8821-6479, Rose, Clair ORCID: https://orcid.org/0000-0001-7782-5359, Aguilera-Flores, Marcela, Portillo, Susana, Verbeelen, Margot, Hussain, Shahid, Smithson, Laura, YuntaYanes, Cristina, Lehane, Mike, Vaughan, Sue, van den Abbeele, Jan, Almeida, Igor C., Boulanger, Martin J. and Acosta-Serrano, Alvaro ORCID: https://orcid.org/0000-0002-2576-7959 (2023) 'The Trypanosoma brucei MISP family of invariant proteins is co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector'. PLoS Pathogens, Vol 19, Issue 3, e1011269.

Preview

Text journal.ppat.1011269.pdf - Published Version Available under License Creative Commons Attribution. Download (3MB) | Preview

Abstract

Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the metacyclic expression of invariant surface antigens. Proteomic analyses of saliva from T. brucei-infected flies identified, in addition to VSG and Brucei Alanine-Rich Protein (BARP) peptides, a family of GPI-anchored surface proteins herein named as Metacyclic Invariant Surface Proteins (MISP) because of its predominant expression on the surface of metacyclic trypomastigotes. The MISP family is encoded by five paralog genes with >80% protein identity, which are exclusively expressed by salivary gland stages of the parasite and peak in metacyclic stage, as shown by confocal microscopy and immuno-high resolution scanning electron microscopy. Crystallographic analysis of a MISP isoform (MISP360) and a high confidence model of BARP revealed a triple helical bundle architecture commonly found in other trypanosome surface proteins. Molecular modelling combined with live fluorescent microscopy suggests that MISP N-termini are potentially extended above the metacyclic VSG coat, and thus could be tested as a transmission-blocking vaccine target. However, vaccination with recombinant MISP360 isoform did not protect mice against a T. brucei infectious tsetse bite. Lastly, both CRISPR-Cas9-driven knock out and RNAi knock down of all MISP paralogues suggest they are not essential for parasite development in the tsetse vector. We suggest MISP may be relevant during trypanosome transmission or establishment in the vertebrate’s skin.

Item Type:	Article
Subjects:	QX Parasitology > QX 20 Research (General) QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors QX Parasitology > Protozoa > QX 70 Mastigophora. (e.g., Giardia. Trichomonas. Trypanosoma. Leishmania)
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.ppat.1011269
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	11 Apr 2023 10:31
Last Modified:	20 Apr 2023 09:00
URI:	https://archive.lstmed.ac.uk/id/eprint/22283

Statistics

View details

Actions (login required)

Edit Item