Abstract：
Antimicrobial peptides, natural or synthetic, appear as promising molecules for antimicrobial therapy because of their both broad antimicrobial activity and mechanism of action. Herein, we determine the anti-Candida and antimycobacterial activities, mechanism of action on yeasts, and cytotoxicity on mammalian cells in the presence of the bioinspired peptide CaDef2.1G27-K44.
CaDef2.1G27-K44 was designed to attain the following criteria: high positive net charge; low molecular weight (<3000 Da); Boman index ≤2.5; and total hydrophobic ratio ≥ 40%. The mechanism of action was studied by growth inhibition, plasma membrane permeabilization, ROS induction, mitochondrial functionality, and metacaspase activity assays. The cytotoxicity on macrophages, monocytes, and erythrocytes were also determined.
CaDef2.1G27-K44 showed inhibitory activity against Candida spp. with MIC100 values ranging from 25 to 50 μM and the standard and clinical isolate of Mycobacterium tuberculosis with MIC50 of 33.2 and 55.4 μM, respectively. We demonstrate that CaDef2.1G27-K44 is active against yeasts at different salt concentrations, induced morphological alterations, caused membrane permeabilization, increased ROS, causes loss of mitochondrial functionality, and activation of metacaspases. CaDef2.1G27-K44 has low cytotoxicity against mammalian cells.
The results obtained showed that CaDef2.1G27-K44 has great antimicrobial activity against Candida spp. and M. tuberculosis with low toxicity to host cells. For Candida spp., the treatment with CaDef2.1G27-K44 induces a process of regulated cell death with apoptosis-like features.
We show a new AMP bioinspired with physicochemical characteristics important for selectivity and antimicrobial activity, which is a promising candidate for drug development, mainly to control Candida infections.
CaDef2.1G27-K44 was designed to attain the following criteria: high positive net charge; low molecular weight (<3000 Da); Boman index ≤2.5; and total hydrophobic ratio ≥ 40%. The mechanism of action was studied by growth inhibition, plasma membrane permeabilization, ROS induction, mitochondrial functionality, and metacaspase activity assays. The cytotoxicity on macrophages, monocytes, and erythrocytes were also determined.
CaDef2.1G27-K44 showed inhibitory activity against Candida spp. with MIC100 values ranging from 25 to 50 μM and the standard and clinical isolate of Mycobacterium tuberculosis with MIC50 of 33.2 and 55.4 μM, respectively. We demonstrate that CaDef2.1G27-K44 is active against yeasts at different salt concentrations, induced morphological alterations, caused membrane permeabilization, increased ROS, causes loss of mitochondrial functionality, and activation of metacaspases. CaDef2.1G27-K44 has low cytotoxicity against mammalian cells.
The results obtained showed that CaDef2.1G27-K44 has great antimicrobial activity against Candida spp. and M. tuberculosis with low toxicity to host cells. For Candida spp., the treatment with CaDef2.1G27-K44 induces a process of regulated cell death with apoptosis-like features.
We show a new AMP bioinspired with physicochemical characteristics important for selectivity and antimicrobial activity, which is a promising candidate for drug development, mainly to control Candida infections.
摘要：
抗菌肽,天然或合成，由于其广泛的抗菌活性和作用机制，因此似乎是抗菌治疗的有希望的分子。在这里，我们确定了抗念珠菌和抗分枝杆菌的活性，对酵母的作用机制，和在生物启发肽CaDef2.1G27-K44存在下对哺乳动物细胞的细胞毒性。
CaDef2.1G27-K44旨在达到以下标准：高净正电荷；低分子量（<3000Da）；Boman指数≤2.5；总疏水比≥40％。通过生长抑制研究了作用机理，质膜透化，ROS诱导,线粒体功能，和metacaspase活性测定。对巨噬细胞的细胞毒性，单核细胞,和红细胞也被测定。
CaDef2.1G27-K44对念珠菌显示出抑制活性。MIC100值范围为25至50μM，结核分枝杆菌的标准和临床分离株MIC50为33.2和55.4μM，分别。我们证明CaDef2.1G27-K44在不同盐浓度下对酵母有活性，诱导的形态学改变，导致膜透化，ROS增加,导致线粒体功能丧失，并激活了β-胱天蛋白酶。CaDef2.1G27-K44对哺乳动物细胞具有低细胞毒性。
结果表明，CaDef2.1G27-K44对念珠菌具有良好的抗菌活性。和对宿主细胞毒性低的结核分枝杆菌。念珠菌属。,CaDef2.1G27-K44治疗诱导具有凋亡样特征的调节细胞死亡过程。
我们展示了一种新的AMP生物启发，具有对选择性和抗菌活性重要的物理化学特性，这是药物开发的一个有希望的候选人，主要控制念珠菌感染。
CaDef2.1G27-K44旨在达到以下标准：高净正电荷；低分子量（<3000Da）；Boman指数≤2.5；总疏水比≥40％。通过生长抑制研究了作用机理，质膜透化，ROS诱导,线粒体功能，和metacaspase活性测定。对巨噬细胞的细胞毒性，单核细胞,和红细胞也被测定。
CaDef2.1G27-K44对念珠菌显示出抑制活性。MIC100值范围为25至50μM，结核分枝杆菌的标准和临床分离株MIC50为33.2和55.4μM，分别。我们证明CaDef2.1G27-K44在不同盐浓度下对酵母有活性，诱导的形态学改变，导致膜透化，ROS增加,导致线粒体功能丧失，并激活了β-胱天蛋白酶。CaDef2.1G27-K44对哺乳动物细胞具有低细胞毒性。
结果表明，CaDef2.1G27-K44对念珠菌具有良好的抗菌活性。和对宿主细胞毒性低的结核分枝杆菌。念珠菌属。,CaDef2.1G27-K44治疗诱导具有凋亡样特征的调节细胞死亡过程。
我们展示了一种新的AMP生物启发，具有对选择性和抗菌活性重要的物理化学特性，这是药物开发的一个有希望的候选人，主要控制念珠菌感染。
