The host phenotype and microbiome varies with infection status, parasite origin and parasite microbiome composition

Background: A growing literature demonstrates the impact of helminths on their host gut microbiome. However, there is now a need to investigate helminth associated microbes and the complex tripartite interactions between parasite, microbes, and hosts. Methods: We investigated whether the stickleback host microbiome depends on eco-evolutionary variables by testing the impact of exposure to the parasite Schistocephalus solidus, infection success, host genotype, parasite genotype, and parasite microbiome composition. Results: We observed constitutive differences in the microbiome of stickleback of different origin that increased when sticklebacks exposed to the parasite resisted infection. In contrast, the microbiome of successfully infected sticklebacks varies with parasite genotype. More specifically, we reveal that the association between microbiome and immune gene expression increases in infected individuals, and varies with parasite genotype. In addition, we showed that S. solidus hosts a complex endo-microbiome and that the abundance and prevalence of an unknown Chloroflexi in the parasite correlate with expression of host immune genes including foxp3, tnfr1, cd97, stat6 and marco. Conclusions: Within this first comprehensive analysis of a cestode’s interaction with bacteria, we demonstrate that (i) regardless of infection success, parasites contribute to modulating the host microbiome, (ii). when infection is successful, the host microbiome varies with parasite genotype due to genotype-dependent variation in parasite immunomodulation, and (iii) the parasite-associated microbiome is distinct from its host’s and contribute to the host immune response to infection. While a growing number of studies focus on determining the genetic and environmental factors contributing to host microbiome composition, this study reveals that parasites, parasite genetic factors, and parasite microbiomes can contribute regardless of whether the infection was successful.

The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype

Host genetic factors can confer resistance against malaria, raising the question of whether this has led to evolutionary adaptation of parasite populations. In this study we investigated the correlation between host and parasite genetic variation in 4,171 Gambian and Kenya children ascertained with severe malaria due to Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and variation in three regions of the parasite genome, including nonsynonymous variants in the acyl-CoA synthetase family member PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The HbS-associated parasite alleles are in strong linkage disequilibrium and have frequencies which covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome, and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.

Variant analysis of the sporozoite surface antigen gene reveals that asymptomatic cattle from wildlife-livestock interface areas in northern Tanzania harbour buffalo-derived T. parva

Buffalo-derived Theileria parva can ‘break through’ the immunity induced by the infection and treatment vaccination method (ITM) in cattle. However, no such ‘breakthroughs’ have been reported in northern Tanzania where there has been long and widespread ITM use in pastoralist cattle, and the Cape buffalo (Syncerus caffer) is also present. We studied the exposure of vaccinated and unvaccinated cattle in northern Tanzania to buffalo-derived T. parva using p67 gene polymorphisms and compared this to its distribution in vaccinated cattle exposed to buffalo-derived T. parva in central Kenya, where vaccine ‘breakthroughs’ have been reported. Additionally, we analysed the CD8+ T cell target antigen Tp2 for positive selection. Our results showed that 10% of the p67 sequences from Tanzanian cattle (n = 39) had a buffalo type p67 (allele 4), an allele that is rare among East African isolates studied so far. The percentage of buffalo-derived p67 alleles observed in Kenyan cattle comprised 19% of the parasites (n = 36), with two different p67 alleles (2 and 3) of presumptive buffalo origin. The Tp2 protein was generally conserved with only three Tp2 variants from Tanzania (n = 33) and five from Kenya (n = 40). Two Tanzanian Tp2 variants and two Kenyan Tp2 variants were identical to variants present in the trivalent Muguga vaccine. Tp2 evolutionary analysis did not show evidence for positive selection within previously mapped epitope coding sites. The p67 data indicates that some ITM-vaccinated cattle are protected against disease induced by a buffalo-derived T. parva challenge in northern Tanzania and suggests that the parasite genotype may represent one factor explaining this.

Genotyping of Parasites: Implications on Clinical Manifestations and Epidemiology

Genotyping is the technology that detects small genetic differences at the level of specific alleles by comparing a DNA sequence to that of another sample or a reference sequence. Genetic variations at a specific allele may lead to change in phenotype of the organisms that determine virulence, drug resistance, immune response, clinical manifestations and transmission. The aim of the talk is to present the basics of genotyping technology and the implications of parasite genotype on clinical manifestations and epidemiology with reference to Toxoplasma gondii.

Tapeworm manipulation of copepod behaviour: parasite genotype has a larger effect than host genotype

Compared with uninfected individuals, infected animals can exhibit altered phenotypes. The changes often appear beneficial to parasites, leading to the notion that modified host phenotypes are extended parasite phenotypes, shaped by parasite genes. However, the phenotype of a parasitized individual may reflect parasitic manipulation, host responses to infection or both, and disentangling the contribution of parasite genes versus host genes to these altered phenotypes is challenging. Using a tapeworm ( Schistocephalus solidus ) infecting its copepod first intermediate host, I performed a full-factorial, cross-infection experiment with five host and five parasite genotypes. I found that a behavioural trait modified by infection, copepod activity, was affected by both host and parasite genotype. There was no clear evidence for host genotype by parasite genotype interactions. Several observations indicated that host behaviour was chiefly determined by parasite genes: (i) all infected copepods, regardless of host or parasite genotype, exhibited behavioural changes, (ii) parasitism reduced the differences among copepod genotypes, and (iii) within infected copepods, parasite genotype had twice as large an effect on behaviour as host genotype. I conclude that the altered behaviour of infected copepods primarily represents an extended parasite phenotype, and I discuss how genetic variation in parasitic host manipulation could be maintained.

Host circadian rhythms are disrupted during malaria infection in parasite genotype-specific manners

Infection can dramatically alter behavioural and physiological traits as hosts become sick and subsequently return to health. Such “sickness behaviours” include disrupted circadian rhythms in both locomotor activity and body temperature. Host sickness behaviours vary in pathogen species-specific manners but the influence of pathogen intraspecific variation is rarely studied. We examine how infection with the murine malaria parasite, Plasmodium chabaudi, shapes sickness in terms of parasite genotype-specific effects on host circadian rhythms. We reveal that circadian rhythms in host locomotor activity patterns and body temperature become differentially disrupted and in parasite genotype-specific manners. Locomotor activity and body temperature in combination provide more sensitive measures of health than commonly used virulence metrics for malaria (e.g. anaemia). Moreover, patterns of host disruption cannot be explained simply by variation in replication rate across parasite genotypes or the severity of anaemia each parasite genotype causes. It is well known that disruption to circadian rhythms is associated with non-infectious diseases, including cancer, type 2 diabetes, and obesity. Our results reveal that disruption of host circadian rhythms is a genetically variable virulence trait of pathogens with implications for host health and disease tolerance.

Within-host interference competition can prevent invasion of rare parasites

Competition between parasite species or genotypes can play an important role in the establishment of parasites in new host populations. Here, we investigate a mechanism by which a rare parasite is unable to establish itself in a host population if a common resident parasite is already present (a ‘priority effect’). We develop a simple epidemiological model and show that a rare parasite genotype is unable to invade if coinfecting parasite genotypes inhibit each other's transmission more than expected from simple resource partitioning. This is because a rare parasite is more likely to be in multiply-infected hosts than the common genotype, and hence more likely to pay the cost of reduced transmission. Experiments competing interfering clones of bacteriophage infecting a bacterium support the model prediction that the clones are unable to invade each other from rare. We briefly discuss the implications of these results for host-parasite ecology and (co)evolution.