Mechanisms of Infection in an Ecological Model of Host-Parasite Interactions
Date
2023-01-09
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Saudi Digital Library
Abstract
Trypanosomatids are evolutionary successful obligate parasites that have two distinct infection life-cycles; some species complete their entire life-cycle in a single host (monoxenous) while others infect two hosts (dixenous). Monoxenous trypanosomtids mostly infect an insect host and are believed to be more primitive and widespread, though not as commonly studied as their dixenous kins. Dixenous trypanosomatids are usually vectored-parasites that encompass etiological agents of several human diseases such African Sleeping Sickness, Chagas disease and Leishmaniasis. Previous studies have examined infection prevalence for subsets of hosts and trypanosomatids, but little is known about whether monoxenous and dixenous trypanosomatids differ in infection prevalence. In chapter 2, I synthesised all published evidence of trypanosomatid infection prevalence for the last two decades using a semi-automated screening protocol. In examining the eligible and included 584 studies that describe infection prevalence, monoxenous species were found to be two-fold more prevalent than dixenous species across all hosts and among insects only. In addition, dixenous trypanosomatids have significantly lower infection prevalence in insects than their non-insect hosts. These results reveal for the first time, a fundamental difference in infection prevalence according to host specificity where vectored species might suffer from lower infection prevalence. These findings will help researchers better understand trypanosomatids in general and further tailor control strategies for various trypanosomatid diseases relevant to human and livestock health.
In the Chapter 3 and Chapter 4, I focused on one monoxenous trypanosomatid, the gut parasite Crithidia bombi and its bumblebee host Bombus terrestris. C. bombi and B. terrestris have become an important model system to study host-parasite interactions and the subsequent ecological and evolutionary aspects of their interactions. In Chapter 2, I infected age-controlled workers of B. terrestris with one genotype of C. bombi (08.076; the reference strain which had been fully sequenced) and dissected their guts at 24 hours, 48 hours and 7 days post infection for full transcriptome sequencing of both the parasite and the host. Differential gene expression comparing (I) late infection versus early infection and (II) for each infection time-point versus pre-infection status (log phase in vitro cultures). I found several upregulated potential virulence genes, based on the orthology to Leishmania major, such as two surface glycoproteins and three calpain family cysteine proteases-like proteins. In addition, parasite genes under positive selection, are more dynamically expressed during all the infection time-points than genes that are not under positive selection. Furthermore, I correlated host immune genes with parasite genes and found that co-regulated host and parasites genes were largely antagonistic (negatively correlated) with distinctive clusters of potential gene-gene interactions. Moreover, I also compared the expression patterns of C. bombi with other dixenous and monoxenous trypanosomatids to examine if differentiation responses are governed by conserved gene expression profiles. Overall, I found a slight but significant predictive power across trypanosomatids that is more pronounced among closer related species. My results help shape a better overall understanding of the co-evolved interactions in this host-parasite system and the breadth of similarity and differences in differentiation responses across trypanosomatids that have distinctive life-cycle strategies.
Co-infection by multiple strains, or species, of parasites can have important implications for both host immune responses and the manifestation of virulence (a feature of infection that is determined by both parasite and host traits). The process by which co-infection arises may also be important in determining these effects. To understand the role of temporal spacing between infectious exposures and parasite genotype in infection, in Chapter 4, I performed a series of within-host competition assays using transmission load (i.e. the number of parasite cells in the infected host’s faeces) as a fitness proxy. My assays show dramatic increase in faecal parasite abundance when hosts are re-infected by the same genotype. Notably, this advantage of repeated exposure only held when host bees were exposed to two doses of the same genotype but not when they were administered together, or when two different genotypes were used in any combination or order of delivery. This suggests a form of immunosuppression leading to genotype specific precedence based facilitation.
Taken together, my work forms a clearer understanding of the previously poorly characterized C. bombi strategies of infection during single and mixed infections. Additionally, the work also highlights a potential fundamental difference between trypanosomatids in infection prevalence based on their life cycle complexity.
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Keywords
trypanosomatids, meta-analysis, infection, parasite, C.bombi, host, expression