Parasites represent the most diverse and adaptable ecological group of the biosphere (Timm & Clauson, 1988; De Meeûs et al., 1998; Poulin & Morand, 2000; De Meeûs & Renaud, 2002). The human species is known to considerably alter biodiversity, though it hosts, and thus sustains the maintenance of a spectacular diversity of parasites (179 species for eukaryotic species only) (De Meeûs et al., 2009). Among these, the five species of malaria agents (genus Plasmodium) remain a major public health issue around the world. Plasmodium falciparum is the most prevalent and lethal of these (Liu et al., 2010). With a pick of up to 2 million deaths due to malaria in 2004, deaths decreased to around 1 million in 2010 (Murray et al., 2012), to reach 619,000 in 2021, most of which in sub-Saharan Africa, and 79% of which were among children aged under 5 years (World Health Organization, 2022). 

            As stressed by Taconet et al. (2023), reduction in malaria deaths is attributable to control measures, in particular against its vectors (mosquitoes of the genus Anopheles). Nevertheless, the success of vector control is hampered by several factors (biological, environmental and socio-economic), and in particular by the great propensity of targeted mosquitoes to evolve physiological or behavioral avoidance of anti-vectorial measures.

            In their paper Taconet et al. (2023) aims at understanding what are the main factors that determine the evolution of insecticide resistance in several malaria vectors, in relation to the biological determinisms of behavioral resistance and how fast such evolutions take place. To tackle these objectives, authors collected an impressive amount of data in two rural areas of West Africa. With appropriate modeling, Taconet et al. discovered, among many other results, a predominant role of public health measures, as compared to agricultural practices, in the evolution of physiological resistance. They also found that mosquito foraging activities are mostly explained by host availability and climate, with a poor, if any, association with genetic markers of physiological resistance to insecticides. These findings represent an important contribution to the field and should help at designing more efficient control strategies against malaria.

References

De Meeûs T, Michalakis Y, Renaud F (1998) Santa Rosalia revisited: or why are there so many kinds of parasites in “the garden of earthly delights”? Parasitology Today, 14, 10–13. https://doi.org/10.1016/S0169-4758(97)01163-0

De Meeûs T, Prugnolle F, Agnew P (2009) Asexual reproduction in infectious diseases. In: Lost Sex: The Evolutionary Biology of Parthenogenesis (eds Schön I, Martens K, van Dijk P), pp. 517-533. Springer, NY. https://doi.org/10.1007/978-90-481-2770-2_24

De Meeûs T, Renaud F (2002) Parasites within the new phylogeny of eukaryotes. Trends in Parasitology, 18, 247–251. https://doi.org/10.1016/S1471-4922(02)02269-9

Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD, Keele BF, Ndjango JB, Sanz CM, Morgan DB, Locatelli S, Gonder MK, Kranzusch PJ, Walsh PD, Delaporte E, Mpoudi-Ngole E, Georgiev AV, Muller MN, Shaw GM, Peeters M, Sharp PM, Rayner JC, Hahn BH (2010) Origin of the human malaria parasite Plasmodium falciparum in gorillas. Nature, 467, 420–425. https://doi.org/10.1038/nature09442

Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD (2012) Global malaria mortality between 1980 and 2010: a systematic analysis. The Lancet, 379, 413–431. https://doi.org/10.1016/S0140-6736(12)60034-8

Poulin R, Morand S (2000) The diversity of parasites. Quarterly Review of Biology, 75, 277–293. https://doi.org/10.1086/393500

Taconet P, Soma DD, Zogo B, Mouline K, Simard F, Koffi AA, Dabire RK, Pennetier C, Moiroux N (2023) Physiological and behavioural resistance of malaria vectors in rural West-Africa : a data mining study to address their fine-scale spatiotemporal heterogeneity, drivers, and predictability. bioRxiv, ver. 4 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2022.08.20.504631

Timm RM, Clauson BL (1988) Coevolution: Mammalia. In: 1988 McGraw-Hill yearbook of science & technology, pp. 212–214. McGraw-Hill Book Company, New York.

World Health Organization (2022) World malaria report 2022. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO. https://iris.who.int/bitstream/handle/10665/365169/9789240064898-eng.pdf?sequence=1.

As recently reported by the world organisation for animal health, 60% of infectious diseases are zoonotic with a significant part associated to ticks. Ticks can transmit various pathogens such as bacteria, viruses and parasites. Among pathogens known to be transmitted by ticks, Ehrlichia ruminantium is an obligate intracellular Gram-negative bacterium responsible for the fatal heartwater disease of domestic and wild ruminants (Allsopp, 2010). E. ruminantium is transmitted by ticks of the genus Amblyomma in the tropical and sub-Saharan areas, as well as in the Caribbean islands. It constitutes a major threat for the American livestock industries since a suitable tick vector is already present in the American mainland and potential introduction of infected A. variegatum through migratory birds or uncontrolled movement of animals from Caribbean could occur (i.e. Deem, 1998 ; Kasari et al 2010). The disease is also a major obstacle to the introduction of animals from heartwater-free to heartwater-infected areas into sub-Saharan Africa and thus restrains breeding programs aiming at upgrading local stocks (Allsopp, 2010).

In this context, it is essential to develop control strategies against heartwater, as developing effective vaccines, for instance. Such an objective requires a better understanding of the early interaction of E. ruminantium and its host cells and of the mechanisms associated with bacterial adhesion to the host-cell. In this study, the authors. studied the role of E. ruminantium membrane protein ERGA_CDS_01230 in the adhesion process to host bovine aortic endothelial cells (BAEC).

After successfully producing the recombinant version of the protein, Pinarello et al (2022) followed the in vitro culture of E. ruminantium in BAEC and observed that the expression of the protein peaked at the extracellular infectious elementary body stages. This result would suggest the likely involvement of the protein in the early interaction of E. ruminantium with its host cells. The authors then showed using flow cytometry, and scanning electron microscopy, that beads coated with the recombinant protein adhered to BAEC. In addition, they also observed that the adhesion protein of E. ruminantium interacted with proteins of the cell's lysate, membrane and organelle fractions. Additionally, enzymatic treatment, degrading dermatan and chondroitin sulfates on the surface of BAEC, was associated with a 50% reduction in the number of bacteria in the host cell after a development cycle, indicating that glycosaminoglycans might play a role in the adhesion of E. ruminantium to the host-cell. Finally, the authors observed that the adhesion protein of E. ruminantium induced a humoral response in vaccinated animals, making this protein a possible vaccine candidate.

As rightly pointed out by both reviewers, the results of this study represent a significant advance (i) in the understanding of the role of the E. ruminantium membrane protein ERGA_CDS_01230 in the adhesion process to the host-cell and (ii) in the development of new control strategies against heartwater as this protein might potentially be used as an immunogen for the development of future vaccines.

References

Allsopp, B.A. (2010). Natural history of Ehrlichia ruminantium. Vet Parasitol 167, 123-135. https://doi.org/10.1016/j.vetpar.2009.09.014

Deem, S.L. (1998). A review of heartwater and the threat of introduction of Cowdria ruminantium and Amblyomma spp. ticks to the American mainland. J Zoo Wildl Med 29, 109-113.

Kasari, T.R. et al (2010). Recognition of the threat of Ehrlichia ruminantium infection in domestic and wild ruminants in the continental United States. J Am Vet Med Assoc. 237:520-30. https://doi.org/10.2460/javma.237.5.520

Pinarello V, Bencurova E, Marcelino I, Gros O, Puech C, Bhide M, Vachiery N, Meyer DF (2022) Ehrlichia ruminantium uses its transmembrane protein Ape to adhere to host bovine aortic endothelial cells. bioRxiv, 2021.06.15.447525, ver. 3 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2021.06.15.447525