Palacios Jacqueline Barrios, Barrios-Payán Jorge, Mata-Espinosa Dulce, Lara-Espinosa Jacqueline V, León-Contreras Juan Carlos, Lushington Gerald H, Melgarejo Tonatiuh, Hernández-Pando Rogelio
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Departamento de Patología Experimental, Vasco de Quiroga 15, Belisario Domínguez Sección 16, Tlalpan, Ciudad de México 14080, Mexico.
Qnapsyn Biosciences, Inc., Lawrence, KS 66044, USA.
Antibiotics (Basel). 2022 Dec 31;12(1):75. doi: 10.3390/antibiotics12010075.
Tuberculosis (TB) is considered the oldest pandemic in human history. The emergence of multidrug-resistant (MDR) strains is currently considered a serious global health problem. As components of the innate immune response, antimicrobial peptides (AMPs) such as cathelicidins have been proposed to have efficacious antimicrobial activity against (). In this work, we assessed a cathelicidin from water buffalo, , (WBCATH), determining in vitro its antitubercular activity (MIC), cytotoxicity and the peptide effect on bacillary loads and cytokines production in infected alveolar macrophages. Our results showed that WBCATH has microbicidal activity against drug-sensitive and MDR , induces structural mycobacterial damage demonstrated by electron microscopy, improves killing and induces the production of protective cytokines by murine macrophages. Furthermore, in vivo WBCATH showed decreased bacterial loads in a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria. In addition, a synergistic therapeutic effect was observed when first-line antibiotics were administered with WBCATH. These results were supported by computational modeling of the potential effects of WBCATH on the cellular membrane of Thus, this water buffalo-derived cathelicidin could be a promising adjuvant therapy for current anti-TB drugs by enhancing a protective immune response and potentially reducing antibiotic treatment duration.
结核病（TB）被认为是人类历史上最古老的大流行病。耐多药（MDR）菌株的出现目前被视为一个严重的全球健康问题。作为先天免疫反应的组成部分，抗菌肽（AMPs）如cathelicidins已被提出对（）具有有效的抗菌活性。在这项工作中，我们评估了一种来自水牛的cathelicidin，即（WBCATH），在体外测定其抗结核活性（MIC）、细胞毒性以及该肽对感染肺泡巨噬细胞中细菌载量和细胞因子产生的影响。我们的结果表明，WBCATH对药物敏感和耐多药的（）具有杀菌活性，通过电子显微镜显示可诱导分枝杆菌结构损伤，提高（）杀伤能力并诱导小鼠巨噬细胞产生保护性细胞因子。此外，在体内，WBCATH在感染药物敏感或耐多药分枝杆菌的BALB/c小鼠的进行性肺结核模型中显示出细菌载量降低。此外，当一线抗生素与WBCATH联合使用时，观察到了协同治疗效果。这些结果得到了WBCATH对（）细胞膜潜在作用的计算模型的支持。因此，这种源自水牛的cathelicidin通过增强保护性免疫反应并可能缩短抗生素治疗时间，可能成为当前抗结核药物的一种有前景的辅助治疗方法。
