Evaluation of anti-malaria potency of wild and genetically modified Enterobacter cloacae expressing effector proteins in Anopheles stephensi

Dehghan, Hossein; Mosa-Kazemi, Seyed Hassan; Yakhchali, Bagher; Maleki‐Ravasan, Naseh; Vatandoost, Hassan; Oshaghi, Mohammad Ali

doi:10.1186/s13071-022-05183-0

Cited by 10 publications

(12 citation statements)

References 73 publications

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“…Thus, the interaction between the gut microbiome of the sand fly host and the Leishmania parasites appears to be beneficial for the parasites. In addition, studies in mosquitoes showed that some gut bacterial species can directly or indirectly reduce [51][52][53][54][55][56][57], or enhance [58][59][60], parasite transmission. Conversely, pathogens such as the malaria parasite and Zika, and Chikungunya viruses can shape the abundance and composition of the mosquito gut microbiome [12,[61][62][63].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

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Comparative analysis of the gut microbiota of sand fly vectors of zoonotic visceral leishmaniasis (ZVL) in Iran; host-environment interplay shapes diversity

et al. 2022

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The development of Leishmania parasites within sand fly vectors occurs entirely in the insect gut lumen, in the presence of symbiotic and commensal bacteria. The impacts of host species and environment on the gut microbiome are currently poorly understood. We employed MiSeq sequencing of the V3-16S rRNA gene amplicons to characterize and compare the gut microbiota of field-collected populations of Phlebotomus kandelakii, P. perfiliewi, P. alexandri, and P. major, the primary or secondary vectors of zoonotic visceral leishmaniasis (ZVL) in three distinct regions of Iran where ZVL is endemic. In total, 160,550 quality-filtered reads of the V3 region yielded a total of 72 operational taxonomic units (OTUs), belonging to 23 phyla, 47 classes, 91 orders, 131 families, and 335 genera. More than 50% of the bacteria identified were Proteobacteria, followed by Firmicutes (22%), Deinococcus-Thermus (9%), Actinobacteria (6%), and Bacteroidetes (5%). The core microbiome was dominated by eight genera: Acinetobacter, Streptococcus, Enterococcus, Staphylococcus, Bacillus, Propionibacterium, Kocuria, and Corynebacterium. Wolbachia were found in P. alexandri and P. perfiliewi, while Asaia sp. was reported in P. perfiliewi. Substantial variations in the gut bacterial composition were found between geographically distinct populations of the same sand fly species, as well as between different species at the same location, suggesting that sand fly gut microbiota is shaped by both the host species and geographical location. Phlebotomus kandelakii and P. perfiliewi in the northwest, and P. alexandri in the south, the major ZVL vectors, harbor the highest bacterial diversity, suggesting a possible relationship between microbiome diversity and the capacity for parasite transmission. In addition, large numbers of gram-positive human or animal pathogens were found, suggesting that sand fly vectors of ZVL could pose a potential additional threat to livestock and humans in the region studied. The presence of Bacillus subtilis, Enterobacter cloacae, and Asaia sp suggests that these bacteria could be promising candidates for a paratransgenesis approach to the fight against Leishmaniasis.

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Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…In addition to B. subtilis, we have isolated Asaia sp. and Enterobacter cloacae from the sand flies, both of which are known to be suitable paratransgenic agents, having previously been used to develop paratransgenic mosquitoes [57,[65][66][67].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Comparative analysis of the gut microbiota of sand fly vectors of zoonotic visceral leishmaniasis (ZVL) in Iran; host-environment interplay shapes diversity

et al. 2022

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“…Therefore, they probably play an essential role in sand fly vector competence for Leishmania parasites ( Louradour et al., 2017 ). Consequently, E. cloacae and B. subtilis can be considered as a shuttle system to deliver, express and spread foreign inserts to be used as promising candidates for the paratransgenic approach ( Hurwitz et al., 2011 ; Dehghan et al., 2017 ; Dehghan et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Co-infection of Phlebotomus papatasi (Diptera: Psychodidae) gut bacteria with Leishmania major exacerbates the pathological responses of BALB/c mice

Amni

Maleki‐Ravasan

Nateghi-Rostami

et al. 2023

Front. Cell. Infect. Microbiol.

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Clinical features and severity of the leishmaniasis is extremely intricate and depend on several factors, especially sand fly-derived products. Bacteria in the sand fly’s gut are a perpetual companion of Leishmania parasites. However, consequences of the concomitance of these bacteria and Leishmania parasite outside the midgut environment have not been investigated in the infection process. Herein, a needle infection model was designed to mimic transmission by sand flies, to examine differences in the onset and progression of L. major infection initiated by inoculation with “low” or “high” doses of Enterobacter cloacae and Bacillus subtilis bacteria. The results showed an alteration in the local expression of pro- and anti-inflammatory cytokines in mice receiving different inoculations of bacteria. Simultaneous injection of two bacteria with Leishmania parasites in the low-dose group caused greater thickness of ear pinna and enhanced tissue chronic inflammatory cells, as well as resulted in multifold increase in the expression of IL-4 and IL-1β and a decrease in the iNOS expression, without changing the L. major burden. Despite advances in scientific breakthroughs, scant survey has investigated the interaction between micro and macro levels of organization of leishmaniasis that ranges from the cellular to macro ecosystem levels, giving rise to the spread and persistence of the disease in a region. Our findings provide new insight into using the potential of the vector-derived microbiota in modulating the vertebrate immune system for the benefit of the host or recommend the use of appropriate antibiotics along with antileishmanial medicines.

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“…Achieving this step could prove complex due to various factors, including the bacteria's ability to persist and successfully establish colonies in the mosquito gut. As the parasite Plasmodium progresses within its invertebrate hosts (vectors), its quantity typically decreases, starting from 103-104 gametocytes and diminishing to 102-103 motile ookinetes, eventually reaching less than 5 oocysts [67]. Targeting and intervening at this bottleneck stage could be crucial in preventing parasite transmission.…”

Section: Resultsmentioning

confidence: 99%

Preliminary in silico study of a novel paratransgenic weapon against malaria

Sun,

Candra,

Pramanda

et al. 2024

ijobas

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Malaria is an infectious disease caused by Plasmodium spp., a protist whose infection is spread by Anopheles mosquito as a vector. A potential method to counter the infection is through paratransgenesis, a promising genetic control approach. This study proposed a new approach by using a transgene carried in a modified Ti plasmid hosted in Asaia bacterium to carry out two purposes: sensing the presence of Plasmodium protein biomarkers and transferring the toxin transgene to the parasite upon detection, thereby killing it without harming the Asaia carrier. The biosensor mechanism was created by repurposing a TonB dependent iron-uptake transport pathway to transcribe the vir genes of Agrobacterium tumefaciens that facilitate the gene transfer. The aim of this in silico project was to serve as a preliminary study on the likelihood of success of the aforementioned biosensor mechanism. This study utilized Alphafold and RCSB (Research Collaboratory for Structural Bioinformatic Protein Data Bank). As for the research tools: PyMOL, ClusPro website, and PRODIGY (PROtein binDIng enerGY prediction) server was used for data preparation, protein-protein docking and binding affinity analysis respectively. The results were assessed with t-test to analyze the significance of the binding affinity, in comparison to other studies that employed similar methods. The result showed Plasmodium protein GGCS (Gamma-glutamylcysteine synthetase) having the highest binding affinity with FecA (Fe(3+) dicitrate transport protein A). The preliminary data suggested that introducing the toxin transgene may be possible through vir gene transcription from the TonB pathway.

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Evaluation of anti-malaria potency of wild and genetically modified Enterobacter cloacae expressing effector proteins in Anopheles stephensi

Cited by 10 publications

References 73 publications

Comparative analysis of the gut microbiota of sand fly vectors of zoonotic visceral leishmaniasis (ZVL) in Iran; host-environment interplay shapes diversity

Comparative analysis of the gut microbiota of sand fly vectors of zoonotic visceral leishmaniasis (ZVL) in Iran; host-environment interplay shapes diversity

Co-infection of Phlebotomus papatasi (Diptera: Psychodidae) gut bacteria with Leishmania major exacerbates the pathological responses of BALB/c mice

Preliminary in silico study of a novel paratransgenic weapon against malaria

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