Aguiar Tawanny K B, Feitosa Ricardo M, Neto Nilton A S, Malveira Ellen A, Gomes Francisco I R, Costa Ana C M, Freitas Cleverson D T, Mesquita Felipe P, Souza Pedro F N
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, Brazil.
Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-275, Brazil.
Antibiotics (Basel). 2023 Jan 27;12(2):256. doi: 10.3390/antibiotics12020256.
is a multidrug-resistant pathogen responsible for infections in immunocompromised patients. Here, itraconazole (ITR), a commercial antifungal drug with low effectiveness against , was combined with different synthetic antimicrobial peptides (SAMPs), Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The Mo-CBP3-PepII was designed based on the sequence of MoCBP3, purified from seeds. RcAlb-PepII and RcAlb-PepIII were designed using Rc-2S-Alb, purified from seed cakes. The putative sequence of a chitinase from was used to design PepGAT and PepKAA. All SAMPs have a positive liquid charge and a hydrophobic potential ranging from 41-65%. The mechanisms of action responsible for the combined effect were evaluated for the best combinations using fluorescence microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against . Our results demonstrated that the combinations could induce pore formation in the membrane and the overaccumulation of ROS on cells. Our findings indicate that our peptides successfully potentialize the activity of ITR against . Therefore, synthetic peptides are potential molecules to assist antifungal agents in treating Cryptococcal infections.
是一种耐多药病原体，可导致免疫功能低下患者发生感染。在此，伊曲康唑（ITR）是一种对其有效性较低的商业抗真菌药物，它与不同的合成抗菌肽（SAMPs），即Mo-CBP3-PepII、RcAlb-PepII、RcAlb-PepIII、PepGAT和PepKAA联合使用。Mo-CBP3-PepII是根据从种子中纯化的MoCBP3序列设计的。RcAlb-PepII和RcAlb-PepIII是使用从籽饼中纯化的Rc-2S-Alb设计的。来自的一种几丁质酶的推测序列用于设计PepGAT和PepKAA。所有SAMPs均带正电荷，疏水势范围为41%-65%。使用荧光显微镜（FM）对最佳组合的联合作用机制进行了评估。合成肽使ITR对的活性提高了10倍。我们的结果表明，这些组合可诱导细胞膜形成孔道，并使细胞上的活性氧过度积累。我们的研究结果表明，我们的肽成功地增强了ITR对的活性。因此，合成肽是协助抗真菌药物治疗隐球菌感染的潜在分子。
