Long live the host! Proteomic analysis reveals possible strategies for parasitic manipulation of its social host

Abstract

Parasites with complex lifecycles are known to manipulate the phenotype of their intermediate hosts to increase the probability of transmission to their definitive hosts. Anomotaenia brevis, a cestode that uses Temnothorax nylanderi ants as intermediate hosts, extends the lifespan of these hosts several fold and changes their behaviour, morphology, and colouration. The mechanisms behind these changes are unknown, as is whether the increased longevity is achieved through manipulation of the parasite. Here we show that the prolonged lifespan of infected ants is probably due to the secretion of antioxidants and possibly novel substances by the parasite. These parasitic proteins make up a substantial portion of the host haemolymph proteome, and thioredoxin peroxidase and superoxide dismutase, two antioxidants, exhibited the highest abundances among them. The largest part of the secreted proteins could not be annotated, indicating they are either novel or severely altered during recent coevolution to function in host manipulation. We found not only secreted proteins, but also shifts in the host proteome, in particular an overabundance of vitellogenin-like A in infected ants, a protein that regulates division of labour in Temnothorax ants, which fits the observed behavioural changes. Our results thus point at two different strategies that are likely employed by this parasite to manipulate its host - by secretion of proteins with immediate influence on the host's phenotype and by altering the host's translational activity. Our results reveal the intricate molecular interplay required to influence host phenotype and shed light on potential signalling pathways and genes.

The influence of parasite load on transcriptional activity and morphology of a cestode and its ant intermediate host

“…Cestodes are known to release vesicles into their environment that contain miRNAs (Ancarola et al, 2020, 2017). In our study system, tetraspanin, a protein considered indicative of extracellular vesicles, was identified among the cestode proteins released into ant haemolymph, suggesting that A. brevis uses this pathway to interact with its host (Hartke et al 2022). A function of extracellular vesicles in parasite-host communication or manipulation has been suggested also in other systems (Coakley, et al, 2015; 2016; Siles-Lucas et al, 2015; Tritten & Geary, 2018), this all points to a need of our parasites living alone to communicate more with (or manipulate) their hosts.…”

“…4c) of these upregulated genes in parasites from highly infected hosts revealed transport functions, among which are carbohydrate transmembrane transport, regulation of pH and sodium ion transport . When comparing these genes to those proteins released into the haemolymph of host ants (Hartke et al 2022) using BLAST, we found three matching genes, none of which were annotated.…”

“…Furthermore, similar to the ant DEGs, we performed enrichment analysis on the extracted KEGG IDs from EGGNOG mapper using clusterProfiler. Finally, to investigate whether some of those genes encode for proteins that are secreted into haemolymph of the host ants (Hartke et al, 2022), we BLASTed (BLAST v.2.9.0; Altschul et al 1990) the cestode DEGs against the RNA sequences of secreated cestode proteins.…”

The influence of parasite load on transcriptional activity and morphology of a cestode and its ant intermediate host

“…The GO enrichment analysis (Figure 4c) of these upregulated genes in parasites from highly infected hosts revealed transport functions, among which are carbohydrate transmembrane transport, regulation of pH and sodium ion transport. When comparing these genes to those proteins released into the haemolymph of host ants (Hartke et al, 2022) using blast, we found three matching genes, none of which were annotated.…”

“…Furthermore, similar to the ant DEGs, we performed enrichment analysis on the extracted KEGG IDs from EGGNOG mapper using clusterProfiler. Finally, to investigate whether some of those genes encode for proteins that are secreted into haemolymph of the host ants (Hartke et al, 2022), we blasted (blast v.2.9.0; Altschul et al, 1990) the cestode DEGs against the RNA sequences of secreted cestode proteins.…”