Fatal attraction evaded. How pathogenic bacteria resist cationic polypeptides.

Fatal attraction evaded. How pathogenic bacteria resist cationic polypeptides.
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DOI:
10.1084/jem.193.9.f31
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发表时间:
2001-05-07
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Ganz T
Ganz T
中科院分区:
其他
文献类型:
--
作者:
Ganz T

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抗菌多肽是广泛分布于动植物体内的一种防御效应物质。包括消化重要微生物结构的酶(如溶菌酶、中性粒细胞弹性蛋白酶、磷脂酶A2)、结合和螯合铁或其他必需营养素的物质(如乳铁蛋白)以及插入和破坏微生物膜的多肽(如杀菌渗透诱导蛋白、防御素、cathelicidin;参考文献1和2)。尽管它们的大小、结构和作用机制不同,但几乎所有的抗微生物蛋白质和肽都具有净阳离子(正)电荷。据认为,阳离子多肽的静电吸引增加了多肽在带负电荷的微生物表面上的沉积,从而促进了它们的有效性。为了支持该模型,大多数但不是所有抗微生物多肽的活性通过增加介质(3-5)的离子强度而被竞争性抑制,所述介质的溶质阴离子和阳离子屏蔽阳离子多肽和阴离子微生物表面的相反电荷并减少它们的相互吸引。微生物已经进化出一系列限制抗菌多肽有效性的对抗措施。细菌对阳离子多肽的抗性可能是由于表面负电荷的丧失,这一早期线索来自荧光假单胞菌暴露于磷酸盐限制。在这些条件下,细菌膜的阴离子磷脂大部分被带正电荷的鸟氨酸修饰的脂质(6)取代,并且细菌变得对阳离子肽抗生素多粘菌素完全具有抗性。在其他研究中,肠道细菌对阳离子抗生素多粘菌素和抗菌肽天蚕素的获得性耐药性与氨基阿拉伯糖含量增加和脂多糖阴离子电荷减少有关(7,8)。
Antimicrobial polypeptides are widely distributed effectors of host defense in animals and plants. They include enzymes that digest vital microbial structures (eg, lysozyme, neutrophil elastase, phospholipase A2), substances that bind and sequester iron or other essential nutrients (eg, lactoferrin), and polypeptides that insert into and disrupt microbial membranes (eg, bactericidal permeability-inducing protein, defensins, cathelicidins; references 1 and 2). Despite their diverse sizes, structures, and mechanisms of action, nearly all antimicrobial proteins and peptides have a net cationic (positive) charge. It is thought that the electrostatic attraction of cationic polypeptides increases the deposition of the polypeptides onto the negatively charged microbial surfaces and thereby promotes their effectiveness. In support of this model, the activity of most but not all antimicrobial polypeptides is competitively inhibited by increasing the ionic strength of the medium (3–5) whose solute anions and cations shield the opposing charges of the cationic polypeptides and anionic microbial surfaces and diminish their mutual attraction. Microbes have evolved a repertoire of countermeasures that limit the effectiveness of antimicrobial polypeptides. Earlier clues that bacterial resistance to cationic polypeptides could be due to the loss of negative surface charges came from exposing Pseudomonas fluorescens to phosphate limitation. Under these conditions, anionic phospholipids of bacterial membranes were largely replaced by positively charged ornithine-modified lipids (6) and the bacteria became completely resistant to the cationic peptide antibiotic polymyxin. In other studies, acquired resistance of enteric bacteria to the cationic antibiotic polymyxin and the antimicrobial peptide cecropin was associated with increased content of aminoarabinose and decreased anionic charge of lipopolysaccharide (7, 8).
组蛋白的杀菌作用。
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