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Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 25410

Special Issue Editor

Special Issue Information

Dear Colleagues,

Vector-borne infectious diseases due to parasites (malaria, leishmaniasis, trypanosomiasis, filariasis...), viruses (chikungunya, dengue, phlebovirus, etc.) or bacteria (bartonellosis, Lyme disease) cause a significant fraction of the global infectious disease burden; indeed, nearly half of the world’s population is infected with at least one type of vector-borne pathogen. An understanding of the molecular basis of interactions between these pathogens and their hosts (vertebrate and invertebrate) would be the rationale for developing new tools that aim at interrupting the transmission process and/or control infection. The goal of the proposed Special Issue on “Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application” is to present recent advances on knowledge on the etiology, pathogenesis, and transmission processes and their translation into tools to detect and combat them. Original articles, reviews, viewpoints, and perspectives focusing on new technological developments and breakthroughs in vector-borne diseases are welcome. Potential topics include but are not limited to biochemistry and molecular biology of pathogens and vectors and their interaction, new technology applied to vector-borne disease diagnosis, novel approaches for blocking disease transmission, studies on the determinants of vectorial competence and prevalence of infections in the field, microbiological or metagenomic analyses of microbiomes associated with vectors, their interaction with pathogens, vaccines, drug development, and drug resistance.

Dr. Denis Sereno
Guest Editor

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Related Special Issue:

“Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application” is a conjunct Special Issue with Microorganisms, and more information may be found at the Special Issue website:

https://www.mdpi.com/journal/microorganisms/special_issues/Epide_Vector_Born_Dis

Keywords

  • vector-borne infectious diseases
  • malaria
  • leishmaniasis
  • trypanosomiasis
  • filariasis
  • molecular basis of interactions
  • pathogens
  • vaccines
  • drug development and resistance
  • arbovirus

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Published Papers (5 papers)

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Research

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19 pages, 3389 KiB  
Article
Functional Characterization of Temporin-SHe, a New Broad-Spectrum Antibacterial and Leishmanicidal Temporin-SH Paralog from the Sahara Frog (Pelophylax saharicus)
by Sonia André, Zahid Raja, Vincent Humblot, Christophe Piesse, Thierry Foulon, Denis Sereno, Bruno Oury and Ali Ladram
Int. J. Mol. Sci. 2020, 21(18), 6713; https://doi.org/10.3390/ijms21186713 - 13 Sep 2020
Cited by 21 | Viewed by 3168
Abstract
Amphibian skin is a promising natural resource for antimicrobial peptides (AMPs), key effectors of innate immunity with attractive therapeutic potential to fight antibiotic-resistant pathogens. Our previous studies showed that the skin of the Sahara Frog (Pelophylax saharicus) contains broad-spectrum AMPs of [...] Read more.
Amphibian skin is a promising natural resource for antimicrobial peptides (AMPs), key effectors of innate immunity with attractive therapeutic potential to fight antibiotic-resistant pathogens. Our previous studies showed that the skin of the Sahara Frog (Pelophylax saharicus) contains broad-spectrum AMPs of the temporin family, named temporins-SH. Here, we focused our study on temporin-SHe, a temporin-SHd paralog that we have previously identified in this frog but was never structurally and functionally characterized. We synthesized and determined the structure of temporin-SHe. This non-amphipathic α-helical peptide was demonstrated to strongly destabilize the lipid chain packing of anionic multilamellar vesicles mimicking bacterial membranes. Investigation of the antimicrobial activity revealed that temporin-SHe targets Gram-negative and Gram-positive bacteria, including clinical isolates of multi-resistant Staphylococcus aureus strains. Temporin-SHe exhibited also antiparasitic activity toward different Leishmania species responsible for visceral leishmaniasis, as well as cutaneous and mucocutaneous forms. Functional assays revealed that temporin-SHe exerts bactericidal effects with membrane depolarization and permeabilization, via a membranolytic mechanism observed by scanning electron microscopy. Temporin-SHe represents a new member of the very limited group of antiparasitic temporins/AMPs. Despite its cytotoxicity, it is nevertheless an interesting tool to study the AMP antiparasitic mechanism and design new antibacterial/antiparasitic agents. Full article
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19 pages, 2030 KiB  
Article
Transcriptome of the Aedes aegypti Mosquito in Response to Human Complement Proteins
by Gloria I. Giraldo-Calderón, Arley Calle-Tobón, Paula Rozo-López, Tonya M. Colpitts, Yoonseong Park, Guillermo L. Rua-Uribe and Berlin Londono-Renteria
Int. J. Mol. Sci. 2020, 21(18), 6584; https://doi.org/10.3390/ijms21186584 - 9 Sep 2020
Cited by 4 | Viewed by 3753
Abstract
Aedes aegypti is the primary mosquito vector of several human arboviruses, including the dengue virus (DENV). Vector control is the principal intervention to decrease the transmission of these viruses. The characterization of molecules involved in the mosquito physiological responses to blood-feeding may help [...] Read more.
Aedes aegypti is the primary mosquito vector of several human arboviruses, including the dengue virus (DENV). Vector control is the principal intervention to decrease the transmission of these viruses. The characterization of molecules involved in the mosquito physiological responses to blood-feeding may help identify novel targets useful in designing effective control strategies. In this study, we evaluated the in vivo effect of feeding adult female mosquitoes with human red blood cells reconstituted with either heat-inactivated (IB) or normal plasma (NB). The RNA-seq based transcript expression of IB and NB mosquitoes was compared against sugar-fed (SF) mosquitoes. In in vitro experiments, we treated Aag2 cells with a recombinant version of complement proteins (hC3 or hC5a) and compared transcript expression to untreated control cells after 24 h. The transcript expression analysis revealed that human complement proteins modulate approximately 2300 transcripts involved in multiple biological functions, including immunity. We also found 161 upregulated and 168 downregulated transcripts differentially expressed when human complement protein C3 (hC3) and human complement protein C5a (hC5a) treated cells were compared to the control untreated cells. We conclude that active human complement induces significant changes to the transcriptome of Ae. aegypti mosquitoes, which may influence the physiology of these arthropods. Full article
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17 pages, 5350 KiB  
Article
Transcriptome Analysis Reveals the Neuro-Immune Interactions in Duck Tembusu Virus-Infected Brain
by Junqin Zhang, Yunzhen Huang, Linlin Li, Jiawen Dong, Ming Liao and Minhua Sun
Int. J. Mol. Sci. 2020, 21(7), 2402; https://doi.org/10.3390/ijms21072402 - 31 Mar 2020
Cited by 13 | Viewed by 3515
Abstract
The duck Tembusu virus (DTMUV) is a mosquito-borne flavivirus. It causes severe symptoms of egg-drop, as well as neurological symptoms and brain damage in ducks. However, the specific molecular mechanisms of DTMUV-induced neurovirulence and host responses in the brain remain obscure. To better [...] Read more.
The duck Tembusu virus (DTMUV) is a mosquito-borne flavivirus. It causes severe symptoms of egg-drop, as well as neurological symptoms and brain damage in ducks. However, the specific molecular mechanisms of DTMUV-induced neurovirulence and host responses in the brain remain obscure. To better understand the host–pathogen and neuro-immune interactions of DTMUV infection, we conducted high-throughput RNA-sequencing to reveal the transcriptome profiles of DTMUV-infected duck brain. Totals of 117, 212, and 150 differentially expressed genes (DEGs) were identified at 12, 24, and 48 h post infection (hpi). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses uncovered genes and pathways related to the nervous system and immune responses in duck brain. Neuro-related genes, including WNT3A, GATA3, and CHRNA6, were found to be significantly downregulated. RIG-I-like receptors (DHX58, IFIH1) and Toll-like receptors (TLR2 and TLR3) were activated, inducing the expression of 22 interferon stimulated genes (ISGs) and antigen-processing and -presenting genes (TAP1 and TAP2) in the brain. Our research provides comprehensive information for the molecular mechanisms of neuro-immune and host–pathogen interactions of DTMUV. Full article
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15 pages, 1893 KiB  
Article
Identification and Pilot Evaluation of Salivary Peptides from Anopheles albimanus as Biomarkers for Bite Exposure and Malaria Infection in Colombia
by Berlin Londono-Renteria, Papa M. Drame, Jehidys Montiel, Ana M. Vasquez, Alberto Tobón-Castaño, Marissa Taylor, Lucrecia Vizcaino and Audrey E. Lenhart
Int. J. Mol. Sci. 2020, 21(3), 691; https://doi.org/10.3390/ijms21030691 - 21 Jan 2020
Cited by 11 | Viewed by 4100
Abstract
Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to [...] Read more.
Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to quantify the intensity of human exposure to Anopheles bites and understand the risk of malaria in low-transmission areas in the Americas. To address this need, we conducted proteomic and bioinformatic analyses of immunogenic candidate proteins present in the saliva of uninfected Anopheles albimanus from two separate colonies—one originating from Central America (STECLA strain) and one originating from South America (Cartagena strain). A ~65 kDa band was identified by IgG antibodies in serum samples from healthy volunteers living in a malaria endemic area in Colombia, and a total of five peptides were designed from the sequences of two immunogenic candidate proteins that were shared by both strains. ELISA-based testing of human IgG antibody levels against the peptides revealed that the transferrin-derived peptides, TRANS-P1, TRANS-P2 and a salivary peroxidase peptide (PEROX-P3) were able to distinguish between malaria-infected and uninfected groups. Interestingly, IgG antibody levels against PEROX-P3 were significantly lower in people that have never experienced malaria, suggesting that it may be a good marker for mosquito bite exposure in naïve populations such as travelers and deployed military personnel. In addition, the strength of the differences in the IgG levels against the peptides varied according to location, suggesting that the peptides may able to detect differences in intensities of bite exposure according to the mosquito population density. Thus, the An. albimanus salivary peptides TRANS-P1, TRANS-P2, and PEROX-P3 are promising biomarkers that could be exploited in a quantitative immunoassay for determination of human-vector contact and calculation of disease risk. Full article
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Review

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49 pages, 4419 KiB  
Review
Noninvasive Biological Samples to Detect and Diagnose Infections due to Trypanosomatidae Parasites: A Systematic Review and Meta-Analysis
by Denis Sereno, Mohammad Akhoundi, Kourosh Sayehmri, Asad Mirzaei, Philippe Holzmuller, Veerle Lejon and Etienne Waleckx
Int. J. Mol. Sci. 2020, 21(5), 1684; https://doi.org/10.3390/ijms21051684 - 29 Feb 2020
Cited by 15 | Viewed by 10258
Abstract
Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they cause requires the sampling of body fluids (e.g., blood, lymph, peritoneal fluid, cerebrospinal fluid) or organ biopsies (e.g., bone [...] Read more.
Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they cause requires the sampling of body fluids (e.g., blood, lymph, peritoneal fluid, cerebrospinal fluid) or organ biopsies (e.g., bone marrow, spleen), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, and Google. The information of each selected article (n = 333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on human African trypanosomiasis and an absence on animal trypanosomiasis. Among the collected data high heterogeneity in terms of the I2 statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigens for leishmaniasis and Chagas disease. Data on conjunctival swabs can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristles showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristles for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites. Full article
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