Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus.

Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus.
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DOI:
10.1186/1471-2180-11-114
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发表时间:
2011-05-23
期刊:
影响因子:
4.2
通讯作者:
van Hoek ML
van Hoek ML
中科院分区:
生物学3区
文献类型:
--
作者:
Dean SN;Bishop BM;van Hoek ML

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慢性感染伤口通常含有多个属的细菌,包括金黄色葡萄球菌,其中许多是强生物膜形成者。细菌生物膜被认为是伤口愈合的直接障碍。专注于生物膜方法的新疗法可能会提高感染伤口的恢复和愈合率。在这项研究中,cathelicidins和相关的短,合成肽的抗微生物的有效性,以及他们的能力,抑制能力的S。金黄色葡萄球菌以形成生物膜。对螺旋状人凯萨林菌素LL-37进行了抗S.金黄色葡萄球菌,并且发现在低μg/ml范围内的浓度下表现出有效的抗微生物、抗附着以及抗生物膜活性。通过使用全D氨基酸肽D-LL-37探索肽手性和相关蛋白酶抗性的影响,并进而与乱序LL-37进行比较。已在其他动物如中华眼镜蛇(Naja atra)(NA-CATH)中鉴定出螺旋状cathelicidin。我们以前确定了一个11个残基不完全重复模式(ATRA基序)内的NA-CATH序列。设计了一系列短肽(ATRA-1、-2、-1A)以及合成肽NA-CATH:ATRA 1-ATRA 1,以探索ATRA基序中保守残基对抗菌活性的意义。NA-CATH和NA-CATH:ATRA 1-ATRA 1的CD光谱揭示了这些肽的结构特性,并表明螺旋性可能是其抗微生物和抗生物膜活性的因素。NA-CATH:ATRA 1-ATRA 1肽抑制S.在盐的存在下,金黄色葡萄球菌在比NA-CATH、LL-37和D-LL-37更低的肽浓度下表现出抗生物膜活性;并且对宿主细胞表现出低细胞毒性,但不影响细菌附着。在这种抗生物膜方法中使用的肽可以为一组新的抗微生物剂和用于治疗慢性伤口感染的潜在的未来局部治疗剂提供模板。
Chronic, infected wounds typically contain multiple genera of bacteria, including Staphylococcus aureus, many of which are strong biofilm formers. Bacterial biofilms are thought to be a direct impediment to wound healing. New therapies that focus on a biofilm approach may improve the recovery and healing rate for infected wounds. In this study, cathelicidins and related short, synthetic peptides were tested for their anti-microbial effectiveness as well as their ability to inhibit the ability of S. aureus to form biofilms. The helical human cathelicidin LL-37 was tested against S. aureus, and was found to exhibit effective anti-microbial, anti-attachment as well as anti-biofilm activity at concentrations in the low μg/ml range. The effect of peptide chirality and associated protease-resistance was explored through the use of an all-D amino acid peptide, D-LL-37, and in turn compared to scrambled LL-37. Helical cathelicidins have been identified in other animals such as the Chinese cobra, Naja atra (NA-CATH). We previously identified an 11-residue imperfectly repeated pattern (ATRA motif) within the sequence of NA-CATH. A series of short peptides (ATRA-1, -2, -1A), as well as a synthetic peptide, NA-CATH:ATRA1-ATRA1, were designed to explore the significance of the conserved residues within the ATRA motif for anti-microbial activity. The CD spectrum of NA-CATH and NA-CATH:ATRA1-ATRA1 revealed the structural properties of these peptides and suggested that helicity may factor into their anti-microbial and anti-biofilm activities. The NA-CATH:ATRA1-ATRA1 peptide inhibits the production of biofilm by S. aureus in the presence of salt, exhibiting anti-biofilm activity at lower peptide concentrations than NA-CATH, LL-37 and D-LL-37; and demonstrates low cytoxicity against host cells but does not affect bacterial attachment. The peptides utilized in this anti-biofilm approach may provide templates for a new group of anti-microbials and potential future topical therapeutics for treating chronic wound infections.
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发表时间: 2003-11-01
期刊: PEPTIDES
影响因子: 3
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发表时间: 2003-09-26
影响因子: 3.1
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