Serna Naroa, Carratalá José Vicente, Conchillo-Solé Oscar, Martínez-Torró Carlos, Unzueta Ugutz, Mangues Ramón, Ferrer-Miralles Neus, Daura Xavier, Vázquez Esther, Villaverde Antonio
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.
Pharmaceutics. 2021 Nov 13;13(11):1922. doi: 10.3390/pharmaceutics13111922.
CXCR4 is a cytokine receptor used by HIV during cell attachment and infection. Overexpressed in the cancer stem cells of more than 20 human neoplasias, CXCR4 is a convenient antitumoral drug target. T22 is a polyphemusin-derived peptide and an effective CXCR4 ligand. Its highly selective CXCR4 binding can be exploited as an agent for the cell-targeted delivery and internalization of associated antitumor drugs. Sharing chemical and structural traits with antimicrobial peptides (AMPs), the capability of T22 as an antibacterial agent remains unexplored. Here, we have detected T22-associated antimicrobial activity and biofilm formation inhibition over , and , in a spectrum broader than the reference AMP GWH1. In contrast to GWH1, T22 shows neither cytotoxicity over mammalian cells nor hemolytic activity and is active when displayed on protein-only nanoparticles through genetic fusion. Under the pushing need for novel antimicrobial agents, the discovery of T22 as an AMP is particularly appealing, not only as its mere addition to the expanding catalogue of antibacterial drugs. The recognized clinical uses of T22 might allow its combined and multivalent application in complex clinical conditions, such as colorectal cancer, that might benefit from the synchronous destruction of cancer stem cells and local bacterial biofilms.
CXCR4是一种细胞因子受体,HIV在细胞附着和感染过程中会利用它。CXCR4在20多种人类肿瘤的癌症干细胞中过表达,是一个方便的抗肿瘤药物靶点。T22是一种源自蚕蛾素的肽,是一种有效的CXCR4配体。其对CXCR4的高度选择性结合可被用作相关抗肿瘤药物细胞靶向递送和内化的试剂。T22与抗菌肽(AMPs)具有共同的化学和结构特征,但其作为抗菌剂的能力尚未得到探索。在这里,我们检测到T22相关的抗菌活性以及对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌生物膜形成的抑制作用,其抗菌谱比参考抗菌肽GWH1更广。与GWH1不同,T22对哺乳动物细胞既无细胞毒性也无溶血活性,并且通过基因融合展示在仅含蛋白质的纳米颗粒上时具有活性。在对新型抗菌剂的迫切需求下,T22作为一种抗菌肽的发现尤其具有吸引力,这不仅是因为它仅仅增加了不断扩大的抗菌药物目录。T22已被认可的临床用途可能使其在复杂的临床病症(如结直肠癌)中联合和多价应用,而这些病症可能受益于癌症干细胞和局部细菌生物膜的同步破坏。