Structural and Biological Characterization of Chromofungin, the Antifungal Chromogranin A-(47–66)-derived Peptide

Lugardon, Karine; Chasserot‐Golaz, Sylvette; Kieffer, Anne-Estelle; Maget‐Dana, Régine; Nullans, Gérard; Kieffer, Bruno; Aunis, Dominique; Metz‐Boutigue, Marie‐Hélène

doi:10.1074/jbc.m104670200

Cited by 88 publications

(71 citation statements)

References 58 publications

(90 reference statements)

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“…Research has demonstrated that the C-terminal moiety of bovine vasostatin-1 has potent antifungal activity. The disulfide bridge loop of Cys 17 -Cys 38 in vasostatin-1 was crucial for its antibacterial activity but not necessary for its antifungal activity (19). To further explore the antifungal activity of the vasostatin-1 derived peptide and avoid aggregation, CGA-N46 which corresponded to human CGA residues 31-76 was synthesized.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei

Li¹,

Zhang²,

Zhang³

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Invasive fungal infections threat the life of immunocompromised patients. Chromogranin A N-46 (CGA-N46), corresponding to the 31st to 76th amino acids of the N-terminus of human chromogranin A, is an antifungal peptide. In order to elucidate the antifungal effects of CGA-N46 in vivo, we studied its effects on cell-mediated immunity in Candida krusei-infected mice. The results showed that the treatment with CGA-N46 increased the average body weight and decreased the mortality of the immunocompromised mice model infected with Candida krusei. The spleen and thymus indices of treated mice has markedly increased compared with that of the control group (P<0.05), and the immune cell levels in peripheral blood also increased significantly (P<0.05). The immuno-modulatory effect of CGA-N46 (60 mg/kg/day) was found to be comparable to that of terbinafine. Additionally, CGA-N46 could alleviate or eliminate histopathological symptoms in the liver, spleen, kidney, and lung tissues. In conclusion, the present study suggests that CGA-N46 may offer a new strategy for antifungal therapeutic option. This study is an essential step in elucidating the effect of CGA-N46 in vivo.

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Section: Introductionmentioning

confidence: 99%

Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei

Li¹,

Zhang²,

Zhang³

et al. 2017

Experimental and Therapeutic Medicine

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show abstract

“…The Pro-adhesive Site Is Distinct from the Anti-adhesive Site-Previous studies suggested that region 47-66 adopts a helical structure (28). Moreover, other studies showed that the 5A8 epitope (RHQNL) includes residues critical for antibody binding (Arg 53 , His 54 , and Leu 57 ) and residues that are less important (Gln 55 and Asn 56 ), the latter being replaced with alanine without loss of binding (32).…”

Section: Cga Inhibits Fibroblast Adhesion and Spreading-we Havementioning

confidence: 99%

“…In addition, it has been shown that chromofungin can inhibit calcineurin, a calmodulin-activated phosphatase (28). Whether the pro-adhesive activity of (STA)1-78 and 48 -68(Y) requires internalization and inhibition of calmodulin-dependent enzymes or not remains to be investigated.…”

Section: -51 (Rilsi)mentioning

confidence: 99%

“…Previous studies showed that a peptide encompassing residues 47-66, called chromofungin, could interact with lipids and penetrate into the cytoplasm of fungi (27,28). In addition, it has been shown that chromofungin can inhibit calcineurin, a calmodulin-activated phosphatase (28).…”

Section: -51 (Rilsi)mentioning

confidence: 99%

“…The structural determinants of these activities are located in different regions of the N-terminal domain. For example, peptide 1-40, containing the Cys 17 -Cys 38 disulfide bridge, induces vasodilator effects and inhibition of parathormone secretion, whereas peptide 47-60 can kill a variety of filamentous fungi (27,28).…”

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confidence: 99%

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Cleavage of Chromogranin A N-terminal Domain by Plasmin Provides a New Mechanism for Regulating Cell Adhesion

Colombo

Longhi

Marinzi

et al. 2002

Journal of Biological Chemistry

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It has been proposed that chromogranin A (CgA), a protein secreted by many normal and neoplastic neuroendocrine cells, can play a role as a positive or a negative modulator of cell adhesion. The mechanisms that regulate these extracellular functions of CgA are unknown. We show here that plasmin can regulate the anti/pro-adhesive activity of CgA by proteolytic cleavage of the N-terminal domain. Limited proteolytic processing decreased its anti-adhesive activity and induced pro-adhesive effects in fibronectin or serum-dependent fibroblast adhesion assays. Cleavage of Lys 77 -Lys 78 dibasic site in CgA 1-115 was relatively rapid and associated with an increase of pro-adhesive effect. In contrast, antibodies against the region 53-90 enhanced the anti-adhesive activity of CgA and CgA 1-115 . Structure-activity relationship studies showed that the conserved region 47-64 (RILSILRHQNLLKELQDL) is critical for both pro-and anti-adhesive activity. These findings suggest that CgA might work on one hand as a negative modulator of cell adhesion and on the other hand as a precursor of positive modulators, the latter requiring proteolytic processing for activation. Given the importance of plasminogen activation in tissue invasion and remodeling, the interplay between CgA and plasmin could provide a novel mechanism for regulating fibroblast adhesion and function in neuroendocrine tumors.

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Self‐Defensive Biomaterial Coating Against Bacteria and Yeasts: Polysaccharide Multilayer Film with Embedded Antimicrobial Peptide

Cado

Aslam

Séon

et al. 2013

Adv Funct Materials

178

155

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Prevention of pathogen colonization of medical implants is a major medical and financial issue since infection by microorganisms constitutes one of the most serious complications after surgery or critical care. Immobilization of antimicrobial molecules on biomaterials surfaces is an efficient approach to prevent biofilm formation. To the best of our knowledge, we developed herein the first self-defensive coating against both bacteria and yeasts where the release of the antimicrobial peptide is triggered by enzymatic degradation of the film due to the pathogens themselves. Biocompatible and biodegradable polysaccharide multilayer films based on functionalized hyaluronic acid by cateslytin (CTL), an endogenous host-defensive antimicrobial peptide, and chitosan (HA-CTL-C/CHI) were deposited on a planar surface with the aim of designing both antibacterial and antifungal coating. After 24 h of incubation, HA-CTL-C/CHI films fully inhibit the development of Gram-positive Staphylococcus aureus bacteria and Candida albicans yeasts, which are common and virulent pathogens agents encountered in care-associated diseases. Hyaluronidase, secreted by the pathogens, leads to the film degradation and the antimicrobial action of the peptide. Furthermore, the limited fibroblasts adhesion on HA-CTL-C/CHI films, without cytotoxicity, highlights a medically relevant application to prevent infections on catheters or tracheal tubes where fibrous tissue encapsulation is undesirable.

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Structural and Biological Characterization of Chromofungin, the Antifungal Chromogranin A-(47–66)-derived Peptide

Cited by 88 publications

References 58 publications

Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei

Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei

Cleavage of Chromogranin A N-terminal Domain by Plasmin Provides a New Mechanism for Regulating Cell Adhesion

Self‐Defensive Biomaterial Coating Against Bacteria and Yeasts: Polysaccharide Multilayer Film with Embedded Antimicrobial Peptide

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