Host-derived lysophosphatidylcholine (LPC) is a significant source of choline and fatty acids for the intraerythrocytic malaria parasite Plasmodium falciparum. Two lysophospholipases play a dominant role in LPC catabolism: exported lipase 2 (XL2) and exported lipase homolog 4 (XLH4). Loss of these two enzymes greatly reduces, but does not abrogate, the parasite's ability to utilize LPC as a source of fatty acids. In this study, we identify a third enzyme, termed "prodrug activation and resistance esterase" (PARE), that mediates low levels of LPC hydrolysis. Loss of PARE alone had no effect on the parasite's ability to scavenge fatty acids from LPC. However, when combined with the loss of XL2 and XLH4, knockdown of PARE impacted the parasite's ability to scavenge both choline and fatty acids from LPC. Furthermore, PARE/XL2/XLH4-deficient parasites were unable to complete a replication cycle when cultured in defined media with LPC as the sole source of exogenous fatty acids. We show that PARE is a membrane-associated enzyme with a substantial presence at the parasite periphery and propose a model whereby PARE catalyzes the hydrolysis of inwardly-diffusing LPC. Our findings reveal that asexual P. falciparum is dependent on parasite-encoded enzymes for LPC catabolism and rule out host erythrocyte enzymes as a physiologically-relevant source of lysophospholipase activity.
Helminth infections persist by influencing host immunity through the release of immunomodulatory proteins which prevent immune ejection. The intestinal nematode Heligmosomoides polygyrus bakeri (Hpb) secretes multiple families of immunomodulatory proteins, many of which are composed of consecutive Complement Control Protein (CCP) domains. We hypothesised that further CCP domain proteins are secreted by the parasite to interact with the host. We identified an unusually large number of CCP domain-containing proteins in the genome of Hpb, and cloned a range of these for screening in an Avidity-based Extracellular Interaction Screening (AVEXIS) assay, focussing on interactions with host immune proteins. This screen confirmed the binding of known immunomodulators (HpBARI, TGM1) for their targets (ST2, TGFBR2) and identified a new interaction between a 2 CCP domain Hpb protein and mouse resistin-like molecule beta (RELMβ), a host protein demonstrated to have anti-helminth properties. This protein was named Binder of RELMβ (HpBoRB). This interaction was specific and heat-labile, and was confirmed in ELISA, competition assays, size exclusion chromatography and surface plasmon resonance experiments, identifying a subnanomolar affinity interaction between HpBoRB and RELMβ. These data may indicate that Hpb interferes with the potent anti-helminth host protein RELMβ and adds to our knowledge of the host-parasite interactions mediated by Hpb secreted proteins.
The assembly of parasite communities is driven by the intricate interplay between geography, climate and host communities, all of which define the range of tick species. Understanding these processes is necessary for uncovering the dynamics behind the circulation of tick-borne pathogens. In this study, we identify traits that define endemicity and ß-diversity patterns in interacting vertebrate and tick communities, based on the distributions of 82 species of ticks and 121 genera of vertebrates across a region that spans the Western Palearctic and the Tropics. Both ß-diversity and endemism exhibit considerable variation between climate regions, with maxima in the Rift Valley, South Africa, and a narrow oceanic band in Namibia. ß-diversity is high in sub-Saharan Africa, and lower in the Western Palearctic. Four chorotypes of co-occurring ticks were identified. Environmental and spatial niche sharing among chorotypes is high, except for certain tick species distributed over the Western Palearctic. Chorotypes display low values of hosts phylogenetic diversity, denoting a low impact of the occurrence of vertebrates on the delineation of chorotypes. Of importance, some ticks that overlap their environmental niche use phylogenetically distant hosts. Chorotypes aid in understanding biodiversity patterns and interactions among hosts and ticks. They are proposed as a framework for investigating the occurrence and spread of tick-borne pathogens. This framework allows a consistent structure for mapping and exploring critical vector-hosts associations in large areas, that could drive key epidemiological patterns of tick-borne diseases.
The southern part of Europe is one of the most species-rich regions from the point of view of the genus and subgenus Ixodes. However, numerous unresolved or questionably interpreted issues exist in the context of tick species indigenous to Mediterranean countries, such as the validity of Ixodes festai, synonymy of Ixodes tatei with Ixodes eldaricus (never tested molecularly) or the haplotype heterogeneity of Ixodes gibbosus. In this study, 21 specimens of six tick species from the subgenus Ixodes were compared morphologically with high resolution digital microscopy and also analyzed with molecular-phylogenetic methods based on two mitochondrial genetic markers. The nymphs of I. eldaricus and I. tatei showed differences in the morphology of the scutum and basis capituli. Both the nymph and the females of I. festai could be distinguished from those of I. eldaricus, I. ventalloi and I. acuminatus. A female tick resembled I. gibbosus but was also different from this species, based on its descriptions. Analysis of phylogenetic relationships confirmed with moderate to strong support that all six species examined in this study represent different taxa of the subgenus Ixodes, including a previously unknown sister species to I. gibbosus. The latter is recognized and described here as a new species, Ixodes paragibbosus Hornok and Kontschán, sp. nov. Based on findings of this study, the tick species I. tatei Arthur, 1959 should be resurrected and reestablished. Morphological and phylogenetic comparisons performed here (including the first barcoding sequences of I. eldaricus and I. festai) confirm that the latter is a valid species, distinct from both I. eldaricus and I. ventalloi. For the differential diagnosis of the above species, the results highlight the importance of observing (among other structures) the auriculae, the internal spur of coxa I and the hypostome.
Trichinella are muscle-dwelling parasitic nematodes that infect a wide range of vertebrate hosts, including humans. Trichinella chanchalensis is a newly recognized species that has been reported in wolverine (Gulo gulo). To investigate the host range of T. chanchalensis we examined the tongue and/or diaphragm from 125 wolverines, 34 red foxes (Vulpes vulpes), 23 Canada lynx (Lynx canadensis), 13 grey wolves (Canis lupus), 10 coyotes (Canis latrans), six black bears (Ursus americanus), one grizzly bear (Ursus arctos), and one polar bear (Ursus maritimus), from Yukon, Canada. Larvae were recovered from tissues by artificial digestion, quantified as larvae per gram (LPG), and genotyped using next-generation sequencing (NGS) on pools of larvae. The parasite intensity of three Trichinella species/genotypes (T. nativa, Trichinella T6, T. chanchalensis) in each sample was estimated by multiplying LPG and relative abundance. Trichinella larvae were detected in 74 % (158/213) of animals and prevalence ranged from 16.7 % in black bears to 86.4 % in wolverines. Median infection intensity was highest in wolverines (13.5 LPG) and lowest in lynx (1.2 LPG), and 92 % of hosts were co-infected with ≥ 2 Trichinella species/genotypes. The parasite intensity of Trichinella T6 was two times greater than T. nativa, and 17 times greater than T. chanchalensis. Trichinella chanchalensis was detected in three new host species including lynx, wolves, and a coyote. There was no significant interaction between Trichinella species/genotype and host species which suggests minimal host specificity. The parasite intensities of T. nativa and T6 were highly positively correlated, which suggests no competition and that infection with one species does not preclude infection by the other species. Our study demonstrates low host specificity and minimal interspecific competition among Trichinella larvae within muscles of naturally co-infected carnivore hosts.
Whirling disease is a debilitating disease of Rainbow Trout caused by Myxobolus cerebralis. The parasite invasion leads to skeletal deformities, neurological impairment, and high mortality. Since its introduction to North America, M. cerebralis has severely impacted wild trout populations in several regions. In this study, we focus on a promising Whirling disease-resistant Rainbow Trout strain developed in the Gunnison River, Colorado. We analyzed the genomes and transcriptomes of this resistant strain at different time points after challenge with M. cerebralis. Signature selection analysis revealed several regions across the genome under selection, with the highest density found on chromosome 23. Several genes found in areas under selection are associated with neuron differentiation and nervous system development. Also, several immuno-genes were under selection, including several with relevance to the innate and adaptive immune response. The transcriptomic analysis revealed that the Gunnison River Rainbow Trout develops a comprehensive immune response after exposure to M. cerebralis. This is supported by the significant enrichment of specific immune response pathways, including differentiation and activation of B-cells and T-cells. These results suggest that certain immune pathways are likely to participate in building the Gunnison River Rainbow Trout's early, mid, and long-term immune response against M. cerebralis, while other pathways related to nervous system development may help juvenile fish survive the effects of Whirling disease. The transcriptomic analysis also reveals that more than half of the top 20 upregulated immune genes are components of the complement pathway. Notably, CD209 (DC-SIGN), a critical gene involved in antigen recognition and dendritic cell function, is among the most highly upregulated genes. The results also indicate the presence of a specific region on chromosome 9 in this strain, previously linked to resistance to this disease. This may explain this strain's strong disease resistance and survival capacity in natural environments.

