Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.
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The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions. (+info)
Structure-antimicrobial activity relationship between pleurocidin and its enantiomer.
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To develop novel antibiotic peptides useful as therapeutic drugs, the enantiomeric analogue of pleurocidin (Ple), which is a well known 25-mer antimicrobial peptide, was designed for proteolytic resistance by D-amino acids substitution. The proteolytic resistance was confirmed by using HPLC after the digestion with various proteases. To investigate the antibiotic effect of L- and D-Ple, the antibacterial activity and hemolytic effect were tested against human erythrocytes. The D-Ple showed a decreased antibacterial activity and a dramatically decreased hemolytic activity compared with L-Ple. The hemolytic effect of analogue was further confirmed by using calcein leakage measurement with liposome. To elucidate these results, the secondary structure of the peptides was investigated by using circular dichroism spectroscopy. The results revealed that D-Ple, as well as L-Ple, had typical alpha-helical structures which were mirror images, with a different helicity. These results suggested that the discrepancy of the structure between the two peptides made their antibacterial activity distinct. (+info)
Investigation of the antifungal activity and mechanism of action of LMWS-chitosan.
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Chitosan, a cationic polysaccharide, has been widely used as a dietary supplement and in a variety of pharmacological and biomedical applications. The antifungal activity and mechanism of action of low molecular weight water-soluble chitosan (LMWS-chitosan) were studied in fungal cells and vesicles containing various compositions of fungal lipids. LMWS-chitosan showed strong antifungal activity against various pathogenic yeasts and hyphae-forming fungi but no hemolytic activity or cytotoxicity against mammalian cells. The degree of calcein leakage was assessed on the basis of lipid composition (PC/CH; 10:1, w/w). Our result showing that LMWS-chitosan interacts with liposomes demonstrated that chitosan induces leakage from zwitterionic lipid vesicles. Confocal microscopy revealed that LMWS-chitosan was located in the plasma membrane. Finally, scanning electron microscopy revealed that LMWS-chitosan causes significant morphological changes on fungal surfaces. Its potent antibiotic activity suggests that LMWS-chitosan is an excellent candidate as a lead compound for the development of novel anti-infective agents. (+info)
Congenital myopathies: a clinicopathological study of 25 cases.
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OBJECTIVE: Congenital myopathies are rare. Through this article, the authors want to present a clinicopathological analysis of 25 new cases. MATERIALS AND METHODS: The clinical data of patients who were diagnosed with congenital myopathy between 2001 and 2006 was retrieved. Muscle biopsies were processed for H&E staining, enzyme histochemistry, and immunohistochemistry. Biopsies were also processed for ultrastructural analysis. RESULTS: During a period of 6 years, 1.12% of the muscle biopsies were diagnosed as congenital myopathies. The most common congenital myopathy was central core disease followed by nemaline rod myopathy and multi-mini core disease. Clinically, they have variable features. The final diagnosis was made with the help of enzyme histochemistry and ultrastructural features. CONCLUSION: This study emphasizes the importance of enzyme histochemistry and electron microscopic examination in the diagnosis of congenital myopathies especially in the absence of genetic studies. (+info)
Therapeutic index of gramicidin S is strongly modulated by D-phenylalanine analogues at the beta-turn.
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Identification of the high affinity binding site in the Streptococcus intermedius toxin intermedilysin for its membrane receptor, the human complement regulator CD59.
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