Kelley Melissa, Sasaninia Kayvan, Badaoui Ali, Glassman Ira, Abnousian Arbi, Rai Nadia, Tiwari Rakesh K, Venketaraman Vishwanath
Department of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States.
Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, United States.
Front Cell Infect Microbiol. 2025 Apr 16;15:1547376. doi: 10.3389/fcimb.2025.1547376. eCollection 2025.
() is a nontuberculous mycobacterium (NTM) that can cause pulmonary and extrapulmonary infections mostly in immunocompromised individuals, such as those with HIV and diabetes. Traditionally, rifampicin (RIF) and azithromycin (AZ) have been used for a 12-month duration as first-line antibiotics against . Due to the increased multidrug resistance, novel ways, such as enhancement of macrophages response, are needed to provide adequate immune response required to clear infection.
In this study, we aim to study the effects of using THP-1 cells, which are monocyte-like cells, to induce a macrophage response and control infection when used in combination with traditional treatments such as RIF and AZ in free and liposomal forms. Traditional treatments' effects are studied when used alone and in combination therapy with cyclic peptide [R4W4] (liposomal encapsulated and liposomal combination). Colony-forming units (CFU) counts were assessed for all samples 3 hours, 4 days, and 8 days post-treatment. A significant reduction in the intracellular viability of was observed when THP-1 cells were treated with liposomal combination [R4W4]+RIF and liposomal combination [R4W4]+AZ compared to when treated with liposomal RIF or liposomal AZ alone, respectively.
Our findings show that liposomal combination [R4W4] is a promising adjuvant therapy to increase susceptibility to known antibiotics.
（）是一种非结核分枝杆菌（NTM），主要可在免疫功能低下的个体中引起肺部和肺外感染，如艾滋病毒感染者和糖尿病患者。传统上，利福平（RIF）和阿奇霉素（AZ）已被用作针对（）的一线抗生素，疗程为12个月。由于多重耐药性增加，需要新的方法，如增强巨噬细胞反应，以提供清除（）感染所需的足够免疫反应。
在本研究中，我们旨在研究使用单核细胞样细胞THP-1诱导巨噬细胞反应，并与游离和脂质体形式的RIF和AZ等传统治疗联合使用时控制（）感染的效果。研究了传统治疗单独使用以及与环肽[R4W4]（脂质体包裹和脂质体组合）联合治疗时的效果。在治疗后3小时、4天和8天对所有样本的菌落形成单位（CFU）计数进行评估。与单独用脂质体RIF或脂质体AZ处理相比，用脂质体组合[R4W4]+RIF和脂质体组合[R4W4]+AZ处理THP-1细胞时，观察到（）的细胞内活力显著降低。
我们的研究结果表明，脂质体组合[R4W4]是一种有前景的辅助治疗方法，可增加（）对已知抗生素的敏感性。
