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Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector–pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations., Graphical Abstract

Development of echinocandin resistance in Candida krusei isolates following exposure to micafungin and caspofungin in a BM transplant unit

Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium falciparum is a common trait in the natural population, and a cluster of natural resistance loci were mapped to the Plasmodium-Resistance Island (PRI) of the A. gambiae genome. The APL1 family of leucine-rich repeat (LRR) proteins was highlighted by candidate gene studies in the PRI, and is comprised of paralogs APL1A, APL1B and APL1C that share ≥50% amino acid identity. Here, we present a functional analysis of the joint response of APL1 family members during mosquito infection with human and rodent Plasmodium species. Only paralog APL1A protected A. gambiae against infection with the human malaria parasite P. falciparum from both the field population and in vitro culture. In contrast, only paralog APL1C protected against the rodent malaria parasites P. berghei and P. yoelii. We show that anti-P. falciparum protection is mediated by the Imd/Rel2 pathway, while protection against P. berghei infection was shown to require Toll/Rel1 signaling. Further, only the short Rel2-S isoform and not the long Rel2-F isoform of Rel2 confers protection against P. falciparum. Protection correlates with the transcriptional regulation of APL1A by Rel2-S but not Rel2-F, suggesting that the Rel2-S anti-parasite phenotype results at least in part from its transcriptional control over APL1A. These results indicate that distinct members of the APL1 gene family display a mutually exclusive protective effect against different classes of Plasmodium parasites. It appears that a gene-for-pathogen-class system orients the appropriate host defenses against distinct categories of similar pathogens. It is known that insect innate immune pathways can distinguish between grossly different microbes such as Gram-positive bacteria, Gram-negative bacteria, or fungi, but the function of the APL1 paralogs reveals that mosquito innate immunity possesses a more fine-grained capacity to distinguish between classes of closely related eukaryotic pathogens than has been previously recognized., Author Summary The African malaria vector mosquito Anopheles gambiae possesses immune mechanisms that can protect it against infection with malaria parasites, which kill more than one million people per year. Much work studying mosquito response to malaria has used model rodent malaria parasites that do not infect people, but are in the same genus and overall share most major features with the human parasites. Here, we show that the immune response used by A. gambiae to protect itself against infection by human and rodent malaria parasites utilizes different immune signaling pathways. A family of proteins called APL1 appears to be responsible for the ability of the mosquito to distinguish between the human or rodent malaria parasites. An individual APL1 relative is required for protection against the human malaria parasite but has no effect against the rodent parasite, and another APL1 relative is required for protection against rodent but not human malaria. This represents the finest ability yet demonstrated of mosquito immunity to distinguish between relatively similar pathogens, and highlights the distinct nature of mosquito response against human as compared to rodent malaria parasites.

Dengue is a re-emerging viral disease, affecting approx. 100 million individuals annually. The monoclonal antibody mAb4E11 neutralizes the four serotypes of the dengue virus, but not other flaviviruses. Its epitope is included within the highly immunogenic domain 3 of the envelope glycoprotein E. To understand the favorable properties of recognition between mAb4E11 and the virus, we recreated the genetic events that led to mAb4E11 during an immune response and performed an alanine scanning mutagenesis of its third hypervariable loops (H-CDR3 and L-CDR3). The affinities between 16 mutant Fab fragments and the viral antigen (serotype 1) were measured by a competition ELISA in solution and their kinetics of interaction by surface plasmon resonance. The diversity and junction residues of mAb4E11 (D segment; V(H)-D, D-J(H) and V(L)-J(L) junctions) constituted major hotspots of interaction energy. Two residues from the D segment (H-Trp96 and H-Glu97) provided85% of the free energy of interaction and were highly accessible to the solvent in a three-dimensional model of mAb4E11. Changes of residues (L-Arg90 and L-Pro95) that statistically do not participate in the contacts between antibodies and antigens but determine the structure of L-CDR3, decreased the affinity between mAb4E11 and its antigen. Changes of L-Pro95 and other neutral residues strongly decreased the rate of association, possibly by perturbing the topology of the electrostatic field of the antibody. These data will help to improve the properties of mAb4E11 for therapeutic applications and map its epitope precisely.

Biosensors for the Environment — Numerous pollutants from industrial or agricultural origins are found in the environment, and especially in water. Compounds such as herbicides, pesticides, chlorinated solvents as well as compounds linked to petroleum utilization are frequently found as pollutants of aquifers. These chemicals are generally toxic for humans and animals and their presence in water must be monitored to avoid the contamination of drinking water sources. Classical analytical tools (GC, GC/MS, etc.) provide accurate, reproducible and sensitive determination of contaminant concentrations. Nevertheless, their use requires to take samples on the contaminated sites and to transport the samples to laboratory for analysis. Such handling of samples is time-consuming and expensive. Biosensors are new analytical tools, whose conception has benefited from advances in different scientific areas, and particularly in biology; they now allow the development of highly specific tools. They provide real-time determination and detection of very low concentrations of contaminant and they can be used directly on-site.