The anti‐endotoxic effects of the KSL‐W decapeptide on <i>Escherichia coli</i> O55:B5 and various oral lipopolysaccharides

Dixon, Douglas R.; Karimi-Naser, Lisa; Darveau, Richard P.; Leung, Kai P.

doi:10.1111/j.1600-0765.2007.01067.x

Cited by 14 publications

(12 citation statements)

References 59 publications

(97 reference statements)

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“…reported that the synthetic AMP KSL-W can bind to the LPS of E . coli and various oral bacteria 14 . Our previous study has demonstrated that N1 can bind LPS and reduce the release of proinflammatory cytokines in LPS-induced acute peritonitis in mice 30 .…”

Section: Discussionmentioning

confidence: 99%

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Antibacterial and detoxifying activity of NZ17074 analogues with multi-layers of selective antimicrobial actions against Escherichia coli and Salmonella enteritidis

Yang

Liu

Teng

et al. 2017

Sci Rep

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NZ17074 (N1), an arenicin-3 derivative isolated from the lugworm, has potent antibacterial activity and is cytotoxic. To reduce its cytotoxicity, seven N1 analogues with different structures were designed by changing their disulfide bonds, hydrophobicity, or charge. The “rocket” analogue-N2 and the “kite” analogue-N6 have potent activity and showed lower cytotoxicity in RAW264.7 cells than N1. The NMR spectra revealed that N1, N2, and N6 adopt β-sheet structures stabilized by one or two disulfide bonds. N2 and N6 permeabilized the outer/inner membranes of E. coli, but did not permeabilize the inner membranes of S. enteritidis. N2 and N6 induced E. coli and S. enteritidis cell cycle arrest in the I-phase and R-phase, respectively. In E. coli and in S. enteritidis, 18.7–43.8% of DNA/RNA/cell wall synthesis and 5.7–61.8% of DNA/RNA/protein synthesis were inhibited by the two peptides, respectively. Collapsed and filamentous E. coli cells and intact morphologies of S. enteritidis cells were observed after treatment with the two peptides. Body weight doses from 2.5–7.5 mg/kg of N2 and N6 enhanced the survival rate of peritonitis- and endotoxemia-induced mice; reduced the serum IL-6, IL-1β and TNF-α levels; and protected mice from lipopolysaccharide-induced lung injury. These data indicate that N2 and N6, through multiple selective actions, may be promising dual-function candidates as novel antimicrobial and anti-endotoxin peptides.

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Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that several α-helical AMPs, such as cathelicidin (LL-37) and KSL-W, can effectively neutralize Porphyromonas gingivalis and E . coli LPS and inhibit LPS-induced inflammatory cytokine production in vitro 13, 14 . Bedran et al .…”

Section: Introductionmentioning

confidence: 99%

Antibacterial and detoxifying activity of NZ17074 analogues with multi-layers of selective antimicrobial actions against Escherichia coli and Salmonella enteritidis

Yang

Liu

Teng

et al. 2017

Sci Rep

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“…Synthetic peptides that mimick many of the key structural features essential for the antimicrobial activity of naturally occurring AMPs have emerged as substitutes against microbial infections. Our laboratories have focused on the antimicrobial activity of synthetic decapeptide KSL and its structural analog KSL-W. We in fact discovered that these peptides possess potent antimicrobial activity against a wide variety of oral and non-oral bacterial pathogens [6,10]. However, their potential effect against fungi, such as C. albicans, remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…In the pursuit of an alternative antifungal treatment, we developed a synthetic ␣-helical antimicrobial decapeptide, KSL (KKVVFKVKFK), and its analog KSL-W (KKVVFWVKFK) [31], that not only display a wide range of antibacterial activity but were shown to effectively kill selected strains of non-oral and oral pathogens, including streptococci mutans. In combination with a surface-active agent, benzalkonium chloride, the peptide significantly reduced in vitro biofilm growth [9,10,23,24].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa

et al. 2011

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We investigated the toxicity of synthetic antimicrobial decapeptide KSL-W on normal human gingival epithelial cell cultures, its effect on Candida albicans adhesion and growth, and the activation of epithelial cell innate immunity. Our results indicate that KSL-W had no toxic effect on cell adhesion or growth, suggesting its safe use with human cells. Pre-treating C. albicans with KSL-W attenuated the yeast's virulence as demonstrated by its reduced adhesion and growth on engineered human oral mucosa epithelium and the subsequent decreased expression of some innate defense molecules by targeted epithelial cells. Indeed, the expression of Toll-like receptors and human β-defensins was reduced in tissues infected with KSL-W-treated Candida. Proinflammatory cytokine secretion (IL-1β and IL-6) by the epithelial cells was also regulated by KSL-W in a manner similar to that of antifungal molecule amphotericin B. These findings therefore show that KSL-W is safe for use with human cells and is able to attenuate Candida virulence by modulating its effects on host innate immunity. This study proposes the potential application of KSL-W peptide as an alternative antifungal agent.

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“…. This synthetic peptide shows a broad range of antimicrobial activity against a number of oral pathogenic bacteria, including S. mutans, S. sobrinus and L. acidophilus 161718. In vitro study demonstrated that KSLW is cytocompatible to normal human gingival epithelial cells19.…”

mentioning

confidence: 99%

Design of a hydroxyapatite-binding antimicrobial peptide with improved retention and antibacterial efficacy for oral pathogen control

Zhibin

Shi

Mao

et al. 2016

Sci Rep

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Controlling and reducing the formation of pathogenic biofilm on tooth surface is the key to the prevention and treatment of the biofilm-associated oral diseases. Antimicrobial peptides (AMPs), considered as possible future alternatives for conventional antibiotics, have been extensively studied for the control of bacterial infection. Due to the rapid dilution and degradation by human saliva, AMP preparations designed for oral use with longer retention and higher efficacy are in urgent need. To this end, a hydroxyapatite (HAp)-binding antimicrobial peptide (HBAMP), which is based on the fusion of a specific HAp-binding heptapeptide (HBP7) domain and a broad-spectrum antimicrobial peptide (KSLW) domain, has been developed in our laboratory. HBAMP was supposed to form a contact-active antibacterial interface on tooth surface to inhibit the formation of biofilms. In this study, we investigated its binding behaviour, antibacterial activity against bacteria in both planktonic and sessile states, enzymatic stability in human saliva, and cytocompatibility to human gingival fibroblasts (HGFs). Our findings suggest that HBAMP could adsorb on tooth surface to provide effective antibacterial activity with improved retention. This study provides a proof-of-concept on using conjugated molecules to promote antibacterial efficacy by synergistically actions of HBAMP free in solution and bound on tooth surface.

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The anti‐endotoxic effects of the KSL‐W decapeptide on Escherichia coli O55:B5 and various oral lipopolysaccharides

Abstract: These results demonstrate that for the concentrations tested, the KSL-W decapeptide was nontoxic to mammalian cells and could bind to and block the host recognition and response towards enteric, as well as oral, lipopolysaccharide samples.

Cited by 14 publications

References 59 publications

Antibacterial and detoxifying activity of NZ17074 analogues with multi-layers of selective antimicrobial actions against Escherichia coli and Salmonella enteritidis

Antibacterial and detoxifying activity of NZ17074 analogues with multi-layers of selective antimicrobial actions against Escherichia coli and Salmonella enteritidis

Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa

Design of a hydroxyapatite-binding antimicrobial peptide with improved retention and antibacterial efficacy for oral pathogen control

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