Gambicin: A novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae (original) (raw)
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Six quality markers were used to plan progress the natural insensitive reaction of the vector mosquito, Anopheles gambiae, on the disease by the intestinal disease parasite, Plasmodium berghei. Notwithstanding the previous four revealed qualities, the arrangement of markers included NOS (part of the nitric oxide synthase quality) and ICHIT (a quality coding two zones supposedly restrictive for chitin isolated by a mucin room rich in polythreonine). In the midgut, 24 hours after the infection, a strong reaction develops as the ookinets of intestinal disorders navigate through the epithel of the midgut but later on during intestinal disease. Our current research was conducted at Services Hospital, Lahore from March 2019 to February 2020. On the other hand, salivary organs do not experience a vital response at 24 hours, but nonetheless are promulgated late, as sporozoites are transferred from midgut to the hemolymph and strike the organ from 12 to 27 days after blood sampling. Moreover, the central portion of the mosquito minus the midgut indicates that marker tolerance is critically applied and that dynamic energy is unmistakable with that of the salivary organs and the midgut. The parasite specifically inspires resistance reactions in various mosquito tissues, all epithelial to the completion of the parasite phase. The ingredients and the basic factor of these reactions are discussed for the transmission of jungle fever.
Insect Biochemistry and Molecular Biology, 2001
A recombinant Anopheles gambiae defensin peptide was used to define the antimicrobial activity spectrum against bacteria, filamentous fungi and yeast. Results showed that most of the Gram-positive bacterial species tested were sensitive to the recombinant peptide in a range of concentrations from 0.1 to 0.75 µM. No activity was detected against Gram-negative bacteria, with the exception of some E. coli strains. Growth inhibitory activity was detected against some species of filamentous fungi. Defensin was not active against yeast. The kinetics of bactericidal and fungicidal effects were determined for Micrococcus luteus and Neurospora crassa, respectively. Differential mass spectrometry analysis was used to demonstrate induction of defensin in the hemolymph of bacteria-infected adult female mosquitoes. Native peptide levels were quantitated in both hemolymph and midgut tissues. The polytene chromosome position of the defensin locus was mapped by in situ hybridization.
Antimicrobial Agents and Chemotherapy, 2002
Insects produce several types of peptides to combat a broad spectrum of invasive pathogenic microbes, including protozoans. However, despite this defense response, infections are often established. Our aim was to design novel peptides that produce high rates of mortality among protozoa of the genus Plasmodium , the malaria parasites. Using existing antimicrobial peptide sequences as templates, we designed and synthesized three short novel hybrids, designated Vida1 to Vida3. Each has a slightly different predicted secondary structure. The peptides were tested against sporogonic stages of the rodent malaria parasites Plasmodium berghei (in vitro and in vivo) and P. yoelii nigeriensis (in vitro). The level of activity varied for each peptide and according to the parasite stage targeted. Vida3 (which is predicted to have large numbers of β sheets and coils but no α helices) showed the highest level of activity, killing the early sporogonic stages in culture and causing highly significan...
Journal of Structural Biology, 2005
Plasmodium falciparum malaria protein peptides were synthesised in the search for more effective routes for inducing a protective immune response against this deadly parasite and this information has been associated with such moleculesÕ three-dimensional structure. These peptides had high red blood cell binding activity and their carboxy-and amino-terminal extremes were elongated for determining their immunogenic and protection-inducing activity against this disease in the Aotus monkey experimental model. 1 H-NMR was used for analysing their three-dimensional structure; FAST ELISA, immunofluorescence antibody test, and Western blot were used for identifying their antibody inducing capacity and these previously immunised Aotus were inoculated with a highly infective P. falciparum strain to determine whether these elongated peptides were able to induce protection. This was aimed at establishing an association or correlation between long peptidesÕ three-dimensional structure and their immunogenic and protection-inducing response in these monkeys. Peptides 20026 (25 residue), 20028 (30 residue), and 20030 (35 residues) were synthesised based on elongating the amino-terminal region of the 10022 highly immunogenic and protection-inducing modified peptide. 1 H-NMR studies revealed that the first three had Classical type III b-turn structures, different from the 20-amino acid long modified peptide 10022 which had a distorted type III b-turn. Humoral immune response analysis showed that even when some antibodies could be generated against the parasite, none of the immunised Aotus could be protected with elongated peptides suggesting that elongating them eliminated modified peptide 10022 immunogenic and protection-inducing capacity.
Anopheles gambiae Immune Responses to Human and Rodent Plasmodium Parasite Species
PLOS Pathogens, 2006
Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence of invading ookinetes, thereby inducing anti-Plasmodium immune responses.
Parasitology Research, 2019
Antimicrobial peptides (AMPs) are important components of the vertebrate and invertebrate innate immune systems. Although AMPs are widely recognized for their broad-spectrum activity against bacteria, fungi, and viruses, their activity against protozoan parasites has not been investigated in detail. In this study, we tested 10 AMPs from three different insect species: the greater wax moth Galleria mellonella (cecropin AD), the fruit fly Drosophila melanogaster (drosocin, Mtk-1 and Mtk-2), and the blow fly Lucilia sericata (LSerPRP-2, LSerPRP-3 and stomoxyn). We tested each AMP against the protozoan parasite Plasmodium falciparum which is responsible for the most severe form of malaria in humans. We also evaluated the impact of these insect AMPs on mouse and pig erythrocytes. Whereas all AMPs showed low hemolytic effects towards mouse and pig erythrocytes, only D. melanogaster Mtk-1 and Mtk-2 significantly inhibited the growth of P. falciparum at low concentrations. Mtk-1 and Mtk-2 could therefore be considered as leads for the development of antiparasitic drugs targeting the clinically important asexual blood stage of P. falciparum.
Insect Biochemistry and Molecular Biology, 2010
The main vector for transmission of malaria in Mexico is the Anopheles albimanus mosquito. The midgut of disease-transmitting mosquitoes carries out a variety of functions that are related to blood feeding. We analyzed the midgut of A. albimanus infected with Plasmodium berghei (resistant mosquito) using a proteomic approach to identify putative short peptides that are enriched in the midgut after blood feeding. Mosquito midguts were analyzed by two-dimensional electrophoresis to determine the changes in protein profiles. We identified 21 spot proteins that are differentially expressed in the blood of mosquitoes during the immune challenge. Molecular weight of the spots varied from 13 to 36 kDa, with a broad isoelectric point range of 3.92e8.90. We identified the differentially expressed proteins using mass spectrometry and constructed a proteomic data base of the A. albimanus midgut with diverse functions, some of them proteins with digestive and immunologic functions. Identification of these proteins may have important implications for understanding the blood meal digestion process, as well as developing novel vector control strategies and understanding parasite vector interactions.