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重组设计宿主防御肽P-诺维丝菌素G10在猪皮肤感染全层伤口中的抗菌活性。

Antimicrobial activity of the recombinant designer host defence peptide P-novispirin G10 in infected full-thickness wounds of porcine skin.

作者信息

Jacobsen F, Mohammadi-Tabrisi A, Hirsch T, Mittler D, Mygind P H, Sonksen C P, Raventos D, Kristensen H H, Gatermann S, Lehnhardt M, Daigeler A, Steinau H U, Steinstraesser L

机构信息

Department of Plastic Surgery, Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum, Buerkle-de-la Camp Platz 1, 44789 Bochum, Germany.

出版信息

J Antimicrob Chemother. 2007 Mar;59(3):493-8. doi: 10.1093/jac/dkl513. Epub 2007 Feb 8.

DOI:10.1093/jac/dkl513
PMID:17289767
Abstract

OBJECTIVES

The growing number of patients with impaired wound healing and the development of multidrug-resistant bacteria demand the investigation of alternatives in wound care. The antimicrobial activity of naturally occurring host defence peptides and their derivatives could be one alternative to the existing therapy options for topical treatment of wound infection. Therefore, the aim of this study was to investigate the antimicrobial activity of proline-novispirin G10 (P-novispirin G10) in vitro and in the infected porcine titanium wound chamber model.

METHODS

The new derived designer host defence peptide P-novispirin G10 was tested in vitro against Gram-positive and Gram-negative bacterial strains. Additionally, cytotoxicity and haemolytic activities of P-novispirin G10 and protegrin-1 were measured. For in vivo studies, six wound chambers were implanted on each flank of Göttinger minipigs (n = 2, female, 6 months old, 15-20 kg). Eleven wound chambers were inoculated 8 days post-operatively with 5 x 10(8) of Staphylococcus aureus; one wound chamber remained uninfected as a system control. After wound infection had been established (4 days after inoculation), each wound chamber was topically treated with P-novispirin G10, protegrin-1 or carrier control. Wound fluid was harvested every hour for a total follow up of 3 h.

RESULTS

P-novispirin G10 demonstrated broad-spectrum antimicrobial activity with moderate haemolytic and cytotoxic activities compared with protegrin-1. In the infected wound chamber model P-novispirin G10 demonstrated a 4 log(10) reduction in bacterial counts.

CONCLUSIONS

This implicates the potential of P-novispirin G10 as an alternative in future antimicrobial wound care. However, more studies are necessary to further define clinical applications and potential side effects in greater detail.

摘要

目的

伤口愈合受损患者数量不断增加,且多重耐药菌不断出现,这就需要对伤口护理的替代方法进行研究。天然存在的宿主防御肽及其衍生物的抗菌活性可能是现有伤口感染局部治疗方案的一种替代方法。因此,本研究的目的是在体外以及感染的猪钛伤口腔模型中研究脯氨酸 - 新诺菌素G10(P - 新诺菌素G10)的抗菌活性。

方法

对新衍生的设计型宿主防御肽P - 新诺菌素G10进行体外抗革兰氏阳性和革兰氏阴性菌株测试。此外,还测量了P - 新诺菌素G10和防御素 - 1的细胞毒性和溶血活性。对于体内研究,在哥廷根小型猪(n = 2,雌性,6个月大,15 - 20千克)的每个侧腹植入6个伤口腔。术后8天,11个伤口腔接种5×10⁸金黄色葡萄球菌;1个伤口腔未感染作为系统对照。伤口感染确立后(接种后4天),每个伤口腔局部用P - 新诺菌素G10、防御素 - 1或载体对照进行治疗。每小时收集伤口液,总共随访3小时。

结果

与防御素 - 1相比,P - 新诺菌素G10表现出广谱抗菌活性,溶血和细胞毒性活性适中。在感染的伤口腔模型中,P - 新诺菌素G10使细菌计数降低了4个对数(10)。

结论

这表明P - 新诺菌素G10有潜力成为未来抗菌伤口护理的替代方法。然而,需要更多研究来进一步详细确定其临床应用和潜在副作用。

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