International Journal of Molecular Sciences

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5 pages, 220 KiB

Open AccessEditorial

Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0

by Denis Sereno

Int. J. Mol. Sci. 2023, 24(9), 7907; https://doi.org/10.3390/ijms24097907 - 26 Apr 2023

Cited by 1 | Viewed by 1303

Abstract

Infectious diseases caused by parasites (malaria, leishmaniasis, trypanosomiasis, filariasis…), viruses (chikungunya, dengue, phlebovirus, etc [...] Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

Research

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24 pages, 3690 KiB

Open AccessArticle

Revealing the Tick Microbiome: Insights into Midgut and Salivary Gland Microbiota of Female Ixodes ricinus Ticks

by Anna Wiesinger, Jasmin Wenderlein, Sebastian Ulrich, Stephanie Hiereth, Lidia Chitimia-Dobler and Reinhard K. Straubinger

Int. J. Mol. Sci. 2023, 24(2), 1100; https://doi.org/10.3390/ijms24021100 - 6 Jan 2023

Cited by 8 | Viewed by 2811

Abstract

The ectoparasite Ixodes ricinus is an important vector for many tick-borne diseases (TBD) in the northern hemisphere, such as Lyme borreliosis, rickettsiosis, human granulocytic anaplasmosis, or tick-borne encephalitis virus. As climate change will lead to rising temperatures in the next years, we expect [...] Read more.

The ectoparasite Ixodes ricinus is an important vector for many tick-borne diseases (TBD) in the northern hemisphere, such as Lyme borreliosis, rickettsiosis, human granulocytic anaplasmosis, or tick-borne encephalitis virus. As climate change will lead to rising temperatures in the next years, we expect an increase in tick activity, tick population, and thus in the spread of TBD. Consequently, it has never been more critical to understand relationships within the microbial communities in ticks that might contribute to the tick’s fitness and the occurrence of TBD. Therefore, we analyzed the microbiota in different tick tissues such as midgut, salivary glands, and residual tick material, as well as the microbiota in complete Ixodes ricinus ticks using 16S rRNA gene amplicon sequencing. By using a newly developed DNA extraction protocol for tick tissue samples and a self-designed mock community, we were able to detect endosymbionts and pathogens that have been described in the literature previously. Further, this study displayed the usefulness of including a mock community during bioinformatic analysis to identify essential bacteria within the tick. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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17 pages, 7940 KiB

Open AccessArticle

Quantum Biochemistry Screening and In Vitro Evaluation of Leishmania Metalloproteinase Inhibitors

by Cláudia Jassica Gonçalves Moreno, Henriqueta Monalisa Farias, Rafael Medeiros, Talita Brito, Johny Oliveira, Francimar Lopes de Sousa, Jr., Mayara Jane Campos de Medeiros, Bruno Amorim, Gabriela Santos-Gomes, Daniel Pontes, Hugo Alexandre Oliveira Rocha, Nilton Fereira Frazao and Marcelo Sousa Silva

Int. J. Mol. Sci. 2022, 23(15), 8553; https://doi.org/10.3390/ijms23158553 - 2 Aug 2022

Cited by 2 | Viewed by 2672

Abstract

Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the [...] Read more.

Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical–computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein–ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with −2 eV, followed by DETC (−1.4 eV), doxycycline (−1.3 eV), and 4-terpineol (−0.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 µM, respectively. L1 induced promastigote forms’ death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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15 pages, 2817 KiB

Open AccessArticle

Predicting Antigenic Peptides from Rocio Virus NS1 Protein for Immunodiagnostic Testing Using Immunoinformatics and Molecular Dynamics Simulation

by Marielena Vogel Saivish, Gabriela de Lima Menezes, Vivaldo Gomes da Costa, Gislaine Celestino Dutra da Silva, Rafael Elias Marques, Maurício Lacerda Nogueira and Roosevelt Alves Da Silva

Int. J. Mol. Sci. 2022, 23(14), 7681; https://doi.org/10.3390/ijms23147681 - 12 Jul 2022

Cited by 4 | Viewed by 2168

Abstract

The mosquito-borne disease caused by the Rocio virus is a neglected threat, and new immune inputs for serological testing are urgently required for diagnosis in low-resource settings and epidemiological surveillance. We used in silico approaches to identify a specific antigenic peptide (p_ROCV2) in [...] Read more.

The mosquito-borne disease caused by the Rocio virus is a neglected threat, and new immune inputs for serological testing are urgently required for diagnosis in low-resource settings and epidemiological surveillance. We used in silico approaches to identify a specific antigenic peptide (p_ROCV2) in the NS1 protein of the Rocio virus that was theoretically predicted to be stable and exposed on its surface, where it demonstrated key properties allowing it to interact with antibodies. These findings related to the molecular dynamics of this peptide provide important insights for advancing diagnostic platforms and investigating therapeutic alternatives. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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16 pages, 2776 KiB

Open AccessArticle

Differences in Charge Distribution in Leishmania tarentolae Leishmanolysin Result in a Reduced Enzymatic Activity

by Vítor Ennes-Vidal, Deborah Antunes, Ester Poláková, Vyacheslav Yurchenko, Simone S. C. Oliveira, Fabio Faria da Mota, Ana Carolina R. Guimaraes, Ernesto R. Caffarena, André L. S. Santos, Marta H. Branquinha and Claudia M. d’Avila-Levy

Int. J. Mol. Sci. 2022, 23(14), 7660; https://doi.org/10.3390/ijms23147660 - 11 Jul 2022

Cited by 3 | Viewed by 1744

Abstract

Leishmania tarentolae is a non-pathogenic trypanosomatid isolated from lizards widely used for heterologous protein expression and extensively studied to understand the pathogenic mechanisms of leishmaniasis. The repertoire of leishmanolysin genes was reported to be expanded in L. tarentolae genome, but no proteolytic activity [...] Read more.

Leishmania tarentolae is a non-pathogenic trypanosomatid isolated from lizards widely used for heterologous protein expression and extensively studied to understand the pathogenic mechanisms of leishmaniasis. The repertoire of leishmanolysin genes was reported to be expanded in L. tarentolae genome, but no proteolytic activity was detected. Here, we analyzed L. tarentolae leishmanolysin proteins from the genome to the structural levels and evaluated the enzymatic activity of the wild-type and overexpressing mutants of leishmanolysin. A total of 61 leishmanolysin sequences were retrieved from the L. tarentolae genome. Five of them were selected for phylogenetic analysis, and for three of them, we built 3D models based on the crystallographic structure of L. major ortholog. Molecular dynamics simulations of these models disclosed a less negative electrostatic potential compared to the template. Subsequently, L. major LmjF.10.0460 and L. tarentolae LtaP10.0650 leishmanolysins were cloned in a pLEXSY expression system into L. tarentolae. Proteins from the wild-type and the overexpressing parasites were submitted to enzymatic analysis. Our results revealed that L. tarentolae leishmanolysins harbor a weak enzymatic activity about three times less abundant than L. major leishmanolysin. Our findings strongly suggest that the less negative electrostatic potential of L. tarentolae leishmanolysin can be the reason for the reduced proteolytic activity detected in this parasite. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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15 pages, 1632 KiB

Open AccessArticle

A Histone Deacetylase (HDAC) Inhibitor with Pleiotropic In Vitro Anti-Toxoplasma and Anti-Plasmodium Activities Controls Acute and Chronic Toxoplasma Infection in Mice

by Delphine Jublot, Pierre Cavaillès, Salima Kamche, Denise Francisco, Diana Fontinha, Miguel Prudêncio, Jean-Francois Guichou, Gilles Labesse, Denis Sereno and Corinne Loeuillet

Int. J. Mol. Sci. 2022, 23(6), 3254; https://doi.org/10.3390/ijms23063254 - 17 Mar 2022

Cited by 10 | Viewed by 2944

Abstract

Toxoplasmosis is a highly prevalent human disease, and virulent strains of this parasite emerge from wild biotopes. Here, we report on the potential of a histone deacetylase (HDAC) inhibitor we previously synthesized, named JF363, to act in vitro against a large panel of [...] Read more.

Toxoplasmosis is a highly prevalent human disease, and virulent strains of this parasite emerge from wild biotopes. Here, we report on the potential of a histone deacetylase (HDAC) inhibitor we previously synthesized, named JF363, to act in vitro against a large panel of Toxoplasma strains, as well as against the liver and blood stages of Plasmodium parasites, the causative agents of malaria. In vivo administration of the drug significantly increases the survival of mice during the acute phase of infection by T. gondii, thus delaying its spreading. We further provide evidence of the compound’s efficiency in controlling the formation of cysts in the brain of T. gondii-infected mice. A convincing docking of the JF363 compound in the active site of the five annotated ME49 T. gondii HDACs was performed by extensive sequence–structure comparison modeling. The resulting complexes show a similar mode of binding in the five paralogous structures and a quite similar prediction of affinities in the micromolar range. Altogether, these results pave the way for further development of this compound to treat acute and chronic toxoplasmosis. It also shows promise for the future development of anti-Plasmodium therapeutic interventions. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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Review

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16 pages, 2414 KiB

Open AccessReview

Status Quo and Future Perspectives of Molecular and Genomic Studies on the Genus Biomphalaria—The Intermediate Snail Host of Schistosoma mansoni

by Ming Fung Franco Au, Gray A. Williams and Jerome H. L. Hui

Int. J. Mol. Sci. 2023, 24(5), 4895; https://doi.org/10.3390/ijms24054895 - 3 Mar 2023

Cited by 6 | Viewed by 5073

Abstract

Schistosomiasis, or also generally known as bilharzia or snail fever, is a parasitic disease that is caused by trematode flatworms of the genus Schistosoma. It is considered by the World Health Organisation as the second most prevalent parasitic disease after malaria and [...] Read more.

Schistosomiasis, or also generally known as bilharzia or snail fever, is a parasitic disease that is caused by trematode flatworms of the genus Schistosoma. It is considered by the World Health Organisation as the second most prevalent parasitic disease after malaria and affects more than 230 million people in over 70 countries. People are infected via a variety of activities ranging from agricultural, domestic, occupational to recreational activities, where the freshwater snails Biomphalaria release Schistosoma cercariae larvae that penetrate the skin of humans when exposed in water. Understanding the biology of the intermediate host snail Biomphalaria is thus important to reveal the potential spread of schistosomiasis. In this article, we present an overview of the latest molecular studies focused on the snail Biomphalaria, including its ecology, evolution, and immune response; and propose using genomics as a foundation to further understand and control this disease vector and thus the transmission of schistosomiasis. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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19 pages, 626 KiB

Open AccessReview

Fatty Acid Composition and Metabolism in Leishmania Parasite Species: Potential Biomarkers or Drug Targets for Leishmaniasis?

by Marine Leroux, Céline Luquain-Costaz, Philippe Lawton, Samira Azzouz-Maache and Isabelle Delton

Int. J. Mol. Sci. 2023, 24(5), 4702; https://doi.org/10.3390/ijms24054702 - 28 Feb 2023

Cited by 5 | Viewed by 2458

Abstract

Fatty acids have received growing interest in Leishmania biology with the characterization of the enzymes allowing the complete fatty acid synthesis of this trypanosomatid parasite. This review presents a comparative analysis of the fatty acid profiles of the major classes of lipids and [...] Read more.

Fatty acids have received growing interest in Leishmania biology with the characterization of the enzymes allowing the complete fatty acid synthesis of this trypanosomatid parasite. This review presents a comparative analysis of the fatty acid profiles of the major classes of lipids and phospholipids in different species of Leishmania with cutaneous or visceral tropism. Specificities relating to the parasite forms, resistance to antileishmanial drugs, and host/parasite interactions are described as well as comparisons with other trypanosomatids. Emphasis is placed on polyunsaturated fatty acids and their metabolic and functional specificities, in particular, their conversion into oxygenated metabolites that are inflammatory mediators able to modulate metacyclogenesis and parasite infectivity. The impact of lipid status on the development of leishmaniasis and the potential of fatty acids as therapeutic targets or candidates for nutritional interventions are discussed. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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22 pages, 1866 KiB

Open AccessReview

Isothermal Nucleic Acid Amplification to Detect Infection Caused by Parasites of the Trypanosomatidae Family: A Literature Review and Opinion on the Laboratory to Field Applicability

by Denis Sereno, Bruno Oury, Anne Geiger, Andrea Vela, Ahmed Karmaoui and Marc Desquesnes

Int. J. Mol. Sci. 2022, 23(14), 7543; https://doi.org/10.3390/ijms23147543 - 7 Jul 2022

Cited by 10 | Viewed by 2532

Abstract

Isothermal amplification of nucleic acids has the potential to be applied in resource-limited areas for the detection of infectious agents, as it does not require complex nucleic purification steps or specific and expensive equipment and reagents to perform the reaction and read the [...] Read more.

Isothermal amplification of nucleic acids has the potential to be applied in resource-limited areas for the detection of infectious agents, as it does not require complex nucleic purification steps or specific and expensive equipment and reagents to perform the reaction and read the result. Since human and animal infections by pathogens of the Tryponasomatidae family occur mainly in resource-limited areas with scant health infrastructures and personnel, detecting infections by these methodologies would hold great promise. Here, we conduct a narrative review of the literature on the application of isothermal nucleic acid amplification for Trypanosoma and Leishmania infections, which are a scourge for human health and food security. We highlight gaps and propose ways to improve them to translate these powerful technologies into real-world field applications for neglected human and animal diseases caused by Trypanosomatidae. Full article

(This article belongs to the Special Issue Molecular Research on Vector-Borne Diseases of Medical Interest: From Bench to Application 2.0)

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