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Lehane, M. J.

Publications and source records attributed to Lehane, M. J..

3 recordsLinked to original sources

The Glossina Genome Cluster: Comparative Genomic Analysis of the Vectors of African Trypanosomes

BackgroundTsetse flies (Glossina sp.) are the sole vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood specific diet by both sexes and obligate bacterial symbiosis. This work describes comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans (G.m. morsitans), G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes) and Fusca (G. brevipalpis) which represent different habitats, host preferences and vectorial capacity. ResultsGenomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex linked scaffolds show increased rates of female specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse specific genes are enriched in protease, odorant binding and helicase activities. Lactation associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other characterized insects. Vision associated Rhodopsin genes show conservation of motion detection/tracking functions and significant variance in the Rhodopsin detecting colors in the blue wavelength ranges. ConclusionsExpanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies.

genomics

Trypanosoma brucei colonises the tsetse gut via an immature peritrophic matrix in the proventriculus

The peritrophic matrix (PM) of haematophagus insects is a chitinous structure that surrounds the bloodmeal, forming a protective barrier against oral pathogens and abrasive particles. To establish an infection in the tsetse midgut, Trypanosoma brucei must colonise the ectoperitrophic space (ES), located between the PM and gut epithelium. Although unproven, it is generally accepted that trypanosomes reach the ES by directly penetrating the PM in the anterior midgut. Here we revisited this event by employing novel fluorescence and electron microscopy methodologies and found that instead, trypanosomes reach the ES via the newly secreted PM in the tsetse proventriculus. Within this model, parasites colonising the proventriculus can either migrate to the ES or become trapped within PM layers forming cysts that move along the entire gut as the PM gets remodelled. Early proventricular colonisation appears to be promoted by unidentified factors in trypanosome-infected blood, resulting in higher salivary gland infections and potentially increasing parasite transmission.

microbiology

The crystal structure and localization of Trypanosoma brucei invariant surface glycoproteins suggest a more permissive VSG coat in the tsetse-transmitted metacyclic stage

Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside the tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, nothing is known about expression of invariant surface antigens by the metacyclic stage. Proteomic analysis of saliva from T. brucei-infected flies revealed a novel family of hypothetical GPI-anchored surface proteins herein named Metacyclic Invariant Surface Proteins (MISP). MISP are encoded by five homolog genes and share ~80% protein identity. The crystal structure of MISP N-terminus at 1.82 [A] resolution revealed a triple helical bundle that shares key features with other trypanosome surface proteins. However, molecular modelling combined with live fluorescent microscopy suggest that MISP N-termini are extended above the metacyclic VSG coat, exposing immunogenic epitopes. Collectively, we suggest that the metacyclic cell surface architecture appears more permissive than bloodstream forms in terms of expression of invariant GPI-anchored glycoproteins, which could be exploited for the development of novel vaccines against African trypanosomiases.

microbiology