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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Biophysical evaluation of cardiolipin content as a regulator of the membrane lytic effect of antimicrobial peptides
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Biophysical evaluation of cardiolipin content as a regulator of the membrane lytic effect of antimicrobial peptides

机译：生物物理评价心脂素含量作为抗菌肽膜裂解效应的调节剂

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Cardiolipin is an anionic tetra-acyl chained glycerophospholipid that increases lipid packing levels and induces intrinsic negative curvature in membranes. Cardiolipin is found in Staphylococcus aureus (S. aureus) membranes, where increased levels of this lipid are induced at the expense of diacyl phosphatidylglycerol in response to stress. We investigate cardiolipin as an inhibitor of the lytic activity of the cationic antimicrobial peptides LL-37 and Delta M2 in model systems with varying phosphatidylglycerol/cardiolipin ratios. Using HPTLC, we show that S. aureus (RN4220), under different growth conditions, has a phosphatidylglycerol/cardiolipin ratio of 80:20. From this, we chose three model systems to evaluate (100:0, 80:20, 60:40). Delta M2 presents higher binding affinity towards all mixtures compared to LL-37. This correlates with the higher antimicrobial activity of Delta M2 compared to LL-37 in S. aureus (MIC90 of 14 mu M for AM2 and 57.7 mu M for LL-37). Laurdan GP shows that Cardiolipin decreases lipid headgroup spacing. We find that cardiolipin does not affect Delta M2 or LL-37 binding to phosphatidylglycerol/cardiolipin liposomes. Instead, cardiolipin inhibits the ability of both peptides to induce calcein leakage in model liposomes. In conclusion, cardiolipin can reduce cAMP activity by inhibiting lysis but not binding.
机译：心肺素是阴离子四酰基链甘油磷脂，其增加了脂质包装水平，并在膜中诱导内在阴性曲率。 Cardiolipin在金黄色葡萄球菌（金黄色葡萄球菌）膜中发现，其中致酸二酰基磷脂酰甘油的牺牲诱导增加该脂质的水平增加。我们将Cardiolipin作为阳离子抗微生物肽LL-37和模型系统中的裂解活性的抑制剂，其在模型系统中具有不同的磷脂酰甘油/心肝脂肪素比的模型系统中。使用HPTLC，我们表明，在不同的生长条件下，S.UUREUS（RN4220）具有80:20的磷脂酰甘油/心肝脂素率。由此，我们选择了三种模型系统来评估（100：0,80:20,60:40）。与LL-37相比，Delta M2对所有混合物具有更高的结合亲和力。与δm2的较高抗微生物活性与Δ-37相比，与β317的Δm2的较高抗微生物活性相关联相关（对于ll-37的am2和57.7μm为14μm的mic90和57.7μm）。 Laurdan GP显示Cardiolipin降低了脂质头组间距。我们发现Cardiolipin不会影响与磷脂酰甘油/心肌脂质体的δM2或LL-37结合。相反，Cardiolipin抑制了肽在模型脂质体中诱导Calcein泄漏的能力。总之，Cardiolipin可以通过抑制裂解而不是结合来减少营养活动。

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