Rat recombinant β-defensin 22 is a heparin-binding protein with antimicrobial activity

Diao, Hua; Yu, Huan; Sun, Fei; Zhang, Yonglian; Tanphaichitr, Nongnuj

doi:10.1038/aja.2010.93

Cited by 18 publications

(20 citation statements)

References 39 publications

(68 reference statements)

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“…However, βD22 LD had no antimicrobial activity against Gc (Figure 7). These results indicate that the defensin domain of βD22 is necessary and sufficient for antigonococcal activity, in agreement with previous findings in E. coli and C. albicans (Diao et al, 2011;Liu et al, 2013).…”

Section: The Defensin-like Domain Is Responsible For the Antigonococcsupporting

confidence: 82%

“…Beyond this, β-defensins within species have highly dissimilar protein sequences (Rao, 2002;Patil et al, 2005). Notably, we found that the antimicrobial activity of βD22 is localized to its defensin domain, as reported for other gram-negative bacteria and fungi (Diao et al, 2011;Liu et al, 2013). The percent identity between βD22 and a canonical β-defensin, βD2, is low (20%).…”

Section: Discussionmentioning

confidence: 89%

“…In this study, we investigated the antimicrobial activity of one of these defensins, β-defensin 22, against Gc. βD22 has been shown to be active against prokaryotic and eukaryotic pathogens (Diao et al, 2011;Liu et al, 2013). However, prior to this study, its activity against pathogens causing STIs had not been examined.…”

Section: Discussionmentioning

confidence: 99%

“…The βD22 lectin domain has been shown to bind the carbohydrate heparin and coat the sperm glycocalyx, which is composed primarily of surface-associated oligosaccharides (Diao et al, 2011;Liu et al, 2013). Given the antimicrobial activity of βD22 against Gc, we hypothesized that the lectin domain of βD22 interacts with the Gc surface, which is largely composed of lipooligosaccharide (LOS) and also has glycosylated proteins.…”

Section: β-Defensin 22 Interacts With the Surface Of N Gonorrhoeae Tmentioning

confidence: 99%

“…The β-defensin domain of human and rat βD22 has been shown to have antimicrobial activity against the fungus Candida albicans, the gram-negative bacterium E. coli, and the gram-positive bacterium Staphylococcus aureus (Diao et al, 2011;Liu et al, 2013). βD22 is preferentially expressed in the reproductive tract of the host (Tollner et al, 2012).…”

Section: Figure 2 Gonorrheal Exudates Contain Numerous Pmns Withmentioning

confidence: 99%

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Neisseria gonorrhoeae Defense against Human Neutrophils and Host-derived Antimicrobials

Handing¹

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Neisseria gonorrhoeae (Gc) is the sole causative agent of the disease gonorrhea. More than 100 million people are infected annually, and reported infection numbers are consistently on the rise. There are clinical isolates of Gc that have developed resistance to the latest third generation cephalosporins, which is the last recommended line of monotherapy for disease treatment, and there is still no available gonococcal vaccine.Following transmission, Gc comes into contact with host mucosal surfaces. Host epithelial cells recognize the pathogen, and respond by releasing both antimicrobials to combat Gc and proinflammatory cytokines to alert the immune system. The cytokine gradient favors recruitment of large numbers of neutrophils to the site of infection. Neutrophils mount a robust immune response characterized by phagocytosis of Gc, production of reactive oxygen species by NADPH oxidase, formation of NETs and release of antimicrobials that are stored in cytoplasmic granules. Despite the potent immune response, Gc resists complete clearance, which suggests that Gc has defensive mechanisms against killing by neutrophils and host-derived antimicrobials at mucosal surfaces. Herein, I investigated the contribution of two important virulence factors, an LOS-modifying enzyme LptA and a clinically relevant antimicrobial efflux pump MtrCDE, for protection of Gc during interactions with human neutrophils. In addition, I explored the antigonococcal activity of a host-derived antimicrobial, β-defensin 22, and characterized its potential for therapeutic application.Gc interactions with neutrophils are not well understood. Though several important observations by our lab and other groups have advanced our understanding, there are still many unknowns.

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Section: The Defensin-like Domain Is Responsible For the Antigonococcsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: β-Defensin 22 Interacts With the Surface Of N Gonorrhoeae Tmentioning

confidence: 99%

Section: Figure 2 Gonorrheal Exudates Contain Numerous Pmns Withmentioning

confidence: 99%

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Neisseria gonorrhoeae Defense against Human Neutrophils and Host-derived Antimicrobials

Handing¹

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Human beta-defensin DEFB126 is capable of inhibiting LPS-mediated inflammation

Liu

et al. 2012

Appl Microbiol Biotechnol

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β-Defensins are cationic, antimicrobial peptides that participate in antimicrobial defense as well as the regulation of innate and adaptive immunity. Human β-defensin 126 (DEFB126) is a multifunctional glycoprotein consisting of a conserved β-defensin core and a unique long glycosylated peptide tail. The long glycosylated peptide tail has been proven to be critical for efficient transport of sperm in the female reproductive tract, preventing their immune recognition, and efficient delivery of capacitated sperm to the site of fertilization. However, the functions of the conserved β-defensin core remain to be fully elucidated. In the present work, the conserved β-defensin core of the DEFB126 was expressed to explore its potential antimicrobial and anti-inflammatory activities. The DEFB126 core peptide exhibited both high potency for binding and neutralizing lipopolysaccharide (LPS) in vitro, and potent anti-inflammatory ability by down-regulating the mRNA expression of pro-inflammatory cytokines including IL-α, IL-1β, IL-6 and TNF-α in a murine macrophage cell line RAW264.7. The treatment with the DEFB126 core peptide also led to correspondingly decreased secretion of IL-6 and TNF-α. The blockade of LPS-induced p42/44 and p38 MAPK signal pathway might contribute to the anti-inflammation effects of the DEFB126 core peptide. Furthermore, fluorescence-labeled DEFB126 could enter RAW 264.7 cells and reduce the production of LPS-stimulated inflammatory factors, implying that DEFB126 might also participate in intracellular regulation beyond its direct LPS neutralization. In summary, our results demonstrate that the DEFB 126 core peptide has critical functions in parallel to its C-terminal tail by showing LPS-binding activity, anti-inflammatory effects and intracellular regulatory function.

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Northeast Red Beans Produce a Thermostable and pH-Stable Defensin-Like Peptide with Potent Antifungal Activity

Chan

2013

Cell Biochem Biophys

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A 5.4-kDa antifungal peptide was purified from Phaseolus vulgaris L. cv. "northeast red bean" using a protocol that entailed affinity chromatography, ion exchange chromatography, and gel filtration. The molecular mass was determined by matrix-assisted laser desorption ionization time-of-flight. The N-terminal amino acid sequence of the peptide was highly homologous to defensins and defensin-like peptides from several plant species. The peptide impeded the growth of a number of pathogenic fungi, including Mycosphaerella arachidicola Khokhr. (IC50 = 1.7 μM), Setosphaeria turcica Luttr., Fusarium oxysporum Schltdl., and Valsa mali Miyabe & G. Yamada. Antifungal activity of the peptide was fully preserved at temperatures up to 100 °C and pH values from 0 to 12. Congo red deposition at the hyphal tip of M. arachidicola was detected after exposure to the peptide, signifying that the peptide had suppressed hyphal growth. The antifungal peptide did not manifest antiproliferative activity toward human breast cancer MCF7 cells and hepatoma HepG2 cells, in contradiction to the bulk of previously reported plant defensins. The data suggest distinct structural requirements for antifungal and antiproliferative activities.

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Rat recombinant β-defensin 22 is a heparin-binding protein with antimicrobial activity

Cited by 18 publications

References 39 publications

Neisseria gonorrhoeae Defense against Human Neutrophils and Host-derived Antimicrobials

Neisseria gonorrhoeae Defense against Human Neutrophils and Host-derived Antimicrobials

Human beta-defensin DEFB126 is capable of inhibiting LPS-mediated inflammation

Northeast Red Beans Produce a Thermostable and pH-Stable Defensin-Like Peptide with Potent Antifungal Activity

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