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      Rodents as vehicle for delivery of transgenic bacteria to make paratransgenic sand fly vectors of cutaneous leishmaniasis in field condition

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          Abstract

          Vector-borne diseases, among them leishmaniasis, cause more than 700,000 deaths annually. The lack of an effective vaccination and the increasing resistance of sand flies to insecticides require the urgent development of innovative approaches to contain the disease. The use of engineered bacteria that express anti-parasite molecules (paratransgenesis) shows much promise. However, a challenge for implementation of this strategy is to devise means to introduce modified bacteria into sand flies in the field. In this study, we use rodent food bait as a delivery strategy to introduce two mCherry-fluorescent bacteria, Serratia AS1 and Enterobacter cloacae, into adult sand flies in field settings. Bacteria-infected food was provided to Rhombomys opimus rodents. These bacteria transiently pass through the rodent alimentary tract and are delivered to larval habitats with the rodent feces. The feces are ingested by sand fly larvae and, in the case of Serratia AS1, are trans-stadially transmitted to adults. This is the first report of targeting delivery of Serratia AS1 in a paratransgenic system to control transmission of leishmaniasis under field condition. This novel strategy shows promise for delivering transgenic bacteria to Leishmania vectors in the field.

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          Leishmaniasis: a review

          Leishmaniasis is caused by an intracellular parasite transmitted to humans by the bite of a sand fly. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year, 350 million are at risk of acquiring the disease, and leishmaniasis causes 70,000 deaths per year. Clinical features depend on the species of Leishmania involved and the immune response of the host. Manifestations range from the localized cutaneous to the visceral form with potentially fatal outcomes. Many drugs are used in its treatment, but the only effective treatment is achieved with current pentavalent antimonials.
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            Dynamic Gut Microbiome across Life History of the Malaria Mosquito Anopheles gambiae in Kenya

            The mosquito gut represents an ecosystem that accommodates a complex, intimately associated microbiome. It is increasingly clear that the gut microbiome influences a wide variety of host traits, such as fitness and immunity. Understanding the microbial community structure and its dynamics across mosquito life is a prerequisite for comprehending the symbiotic relationship between the mosquito and its gut microbial residents. Here we characterized gut bacterial communities across larvae, pupae and adults of Anopheles gambiae reared in semi-natural habitats in Kenya by pyrosequencing bacterial 16S rRNA fragments. Immatures and adults showed distinctive gut community structures. Photosynthetic Cyanobacteria were predominant in the larval and pupal guts while Proteobacteria and Bacteroidetes dominated the adult guts, with core taxa of Enterobacteriaceae and Flavobacteriaceae. At the adult stage, diet regime (sugar meal and blood meal) significantly affects the microbial structure. Intriguingly, blood meals drastically reduced the community diversity and favored enteric bacteria. Comparative genomic analysis revealed that the enriched enteric bacteria possess large genetic redox capacity of coping with oxidative and nitrosative stresses that are associated with the catabolism of blood meal, suggesting a beneficial role in maintaining gut redox homeostasis. Interestingly, gut community structure was similar in the adult stage between the field and laboratory mosquitoes, indicating that mosquito gut is a selective eco-environment for its microbiome. This comprehensive gut metatgenomic profile suggests a concerted symbiotic genetic association between gut inhabitants and host.
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              Mosquitoes rely on their gut microbiota for development.

              Field studies indicate adult mosquitoes (Culicidae) host low diversity communities of bacteria that vary greatly among individuals and species. In contrast, it remains unclear how adult mosquitoes acquire their microbiome, what influences community structure, and whether the microbiome is important for survival. Here, we used pyrosequencing of 16S rRNA to characterize the bacterial communities of three mosquito species reared under identical conditions. Two of these species, Aedes aegypti and Anopheles gambiae, are anautogenous and must blood-feed to produce eggs, while one, Georgecraigius atropalpus, is autogenous and produces eggs without blood feeding. Each mosquito species contained a low diversity community comprised primarily of aerobic bacteria acquired from the aquatic habitat in which larvae developed. Our results suggested that the communities in Ae. aegypti and An. gambiae larvae share more similarities with one another than with G. atropalpus. Studies with Ae. aegypti also strongly suggested that adults transstadially acquired several members of the larval bacterial community, but only four genera of bacteria present in blood fed females were detected on eggs. Functional assays showed that axenic larvae of each species failed to develop beyond the first instar. Experiments with Ae. aegypti indicated several members of the microbial community and Escherichia coli successfully colonized axenic larvae and rescued development. Overall, our results provide new insights about the acquisition and structure of bacterial communities in mosquitoes. They also indicate that three mosquito species spanning the breadth of the Culicidae depend on their gut microbiome for development. © 2014 John Wiley & Sons Ltd.
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                Author and article information

                Contributors
                aaakhavan@sina.tums.ac.ir
                moshaghi@sina.tums.ac.ir
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 September 2023
                9 September 2023
                2023
                : 13
                : 14912
                Affiliations
                [1 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Vector Biology and Control of Diseases, School of Public Health, , Tehran University of Medical Sciences, ; Tehran, Islamic Republic of Iran
                [2 ]GRID grid.419420.a, ISNI 0000 0000 8676 7464, Institute of Industrial and Environmental Biotechnology, , National Institute of Genetic Engineering and Biotechnology (NIGEB), ; Tehran, Islamic Republic of Iran
                [3 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Isfahan Health Research Station, School of Public Health, , Tehran University of Medical Sciences, ; Tehran, Islamic Republic of Iran
                [4 ]GRID grid.412105.3, ISNI 0000 0001 2092 9755, Department of Vector Biology and Control, Faculty of Public Health, , Kerman University of Medical Sciences, ; Kerman, Islamic Republic of Iran
                [5 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Biostatistics, School of Public Health, , Tehran University of Medical Sciences, ; Tehran, Islamic Republic of Iran
                Article
                41526
                10.1038/s41598-023-41526-2
                10492802
                37689736
                2cac5579-e9c3-49ac-b1ed-237f1aa35452
                © Springer Nature Limited 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 June 2023
                : 28 August 2023
                Funding
                Funded by: National Institutes for Medical Research Development (NIMAD)
                Award ID: 989593
                Award Recipient :
                Funded by: Tehran University of Medical Sciences, Iran
                Award ID: 48901
                Award Recipient :
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                © Springer Nature Limited 2023

                Uncategorized
                microbiology,molecular biology,diseases
                Uncategorized
                microbiology, molecular biology, diseases

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