Antifungal Activities of Human Beta-Defensins HBD-1 to HBD-3 and Their C-Terminal Analogs Phd1 to Phd3

Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 10/2008; 53(1):256-60. DOI: 10.1128/AAC.00470-08
Source: PubMed Central


The activities of defensins HBD-1, HBD-2, and HBD-3 and their C-terminal analogs Phd1, Phd2, and Phd3 against Candida albicans were investigated. Phd1 to Phd3 showed lower-level activities than HBD-1 to HBD-3, although metabolic inhibitors did not render Phd1 to Phd3 inactive. Their activities were also less salt sensitive than those of HBD-1 to HBD-3. Confocal microscope images indicated that the initial site of action was the fungal membrane. Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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    • "For example, HNP-1, HNP-5 and human beta-defensins 1 and 3 (HBD1 and HBD3, respectively) have broad antimicrobial activities against Gram-negative and Gram-positive bacteria and yeasts (Ganz et al., 1985; Bensch et al., 1995; Porter et al., 1997; Harder et al., 2001; Hoover et al., 2003; Joly et al., 2004). HBD1 and HBD3 have been shown to be effective against C. albicans (Krishnakumari et al., 2009), while HBD2 has been shown to possess significant microbicidal activity against Gram-negative bacteria and C. albicans (Schroder and Harder, 1999). Recombinant human intestinal defensin 5 (rHD-5) exhibits microbicidal activity against Listeria monocytogenes, Escherichia coli, and C. albicans. "
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    ABSTRACT: Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed.
    Full-text · Article · Mar 2014 · Frontiers in Microbiology
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    • "Several studies have indicated that all the three disulfide bridges are not required for exhibiting antimicrobial activity in HBD-1-3 [19-29]. The effect of substituting L- by D-amino acids in α- and β-defensins has been examined. "
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    ABSTRACT: We have examined the antimicrobial activity of C-terminal analogs of human β-defensins HBD-1and-3 wherein lysines have been selectively replaced by L- and D-arginines and L-isoleucine substituted with its D-enantiomer. The analogs exhibited antibacterial and antifungal activities. Physiological concentration of NaCl did not attenuate the activity of the peptides against Gram-negative bacteria considerably, while some attenuation of activity was observed against S. aureus. Variable attenuation of activity was observed in the presence of Ca(2+) and Mg(2+). Introduction of D-amino acids abrogated the need for a disulfide bridge for exhibiting activity. Confocal images of carboxyfluorescein (CF) labeled peptides indicated initial localization on the membrane and subsequent translocation into the cell. Analogs corresponding to cationic rich segments of human defensins substituted with L- and D-arginine, could be attractive candidates for development as future therapeutic drugs.
    Preview · Article · Sep 2013 · PLoS ONE
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    • "HBDs exhibit anti-fungal activity against Candidas spp, including C. albicans[33-35], therefore, the rationale for the present study was to test the individual contribution of the amnion and the choriodecidual regions to the secretion of HBD-1, -2, and -3 after stimulation with Candida albicans. Our findings suggest that HBD-1-3 may provide protection against penetration by microorganisms into the immune-privileged amniotic cavity. "
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    ABSTRACT: Background During intrauterine infection, amniochorionic membranes represent a mechanical and immunological barrier against dissemination of infection. Human beta defensins (HBD)-1, HBD-2, and HBD-3 are key elements of innate immunity that represent the first line of defense against different pathogen microorganisms associated with preterm labor. The aim of this work was to characterize the individual contribution of the amnion (AMN) and choriodecidua (CHD) regions to the secretion of HBD-1, HBD-2 and HBD-3, after stimulation with Candida albicans. Methods Full-thickness human amniochorionic membranes were obtained after delivery by elective cesarean section from women at 37-40 wk of gestation with no evidence of active labor. The membranes were cultured in a two-compartment experimental model in which the upper compartment is delimited by the amnion and the lower chamber by the choriodecidual membrane. One million of Candida albicans were added to either the AMN or the CHD face or to both and compartmentalized secretion profiles of HBD-1, HBD-2, and HBD-3 were quantified by ELISA. Tissue immunolocalization was performed to detect the presence of HBD-1, -2, -3 in tissue sections stimulated with Candida albicans. Results HBD-1 secretion level by the CHD compartment increased 2.6 times (27.30 [20.9-38.25] pg/micrograms protein) when the stimulus with Candida albicans was applied only on this side of the membrane and 2.4 times (26.55 [19.4-42.5] pg/micrograms protein) when applied to both compartments simultaneously. HBD-1 in the amniotic compartment remained without significant changes. HBD-2 secretion level increased significantly in the CHD when the stimulus was applied only to this region (2.49 [1.49-2.95] pg/micrograms protein) and simultaneously to both compartments (2.14 [1.67- 2.91] pg/micrograms protein). When the stimulus was done in the amniotic compartment HBD-2 remained without significant changes in both compartments. HBD-3 remained without significant changes in both compartments regardless of the stimulation modality. Localization of immune-reactive forms of HBD-1, HBD-2, and HBD-3 was carried out by immunohistochemistry confirming the cellular origin of these peptides. Conclusion Selective stimulation of amniochorionic membranes with Candida albicans resulted in tissue-specific secretion of HBD-1 and HBD-2, mainly in the CHD, which is the first region to become infected during an ascending infection.
    Full-text · Article · Sep 2012 · Reproductive Biology and Endocrinology
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