Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville South, Australia; The University of Adelaide, Adelaide, Australia.
Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville South, Australia; The University of Adelaide, Adelaide, Australia; Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, Al-Azhar University, Assiut, Egypt.
Tuberculosis (Edinb). 2023 Sep;142:102390. doi: 10.1016/j.tube.2023.102390. Epub 2023 Jul 24.
Non-Tuberculous Mycobacterial Pulmonary Disease (NTM-PD) caused by Mycobacterium abscessus is a frequent complication in patients with cystic fibrosis (CF) that worsens lung function over time. Currently, there is no cure for NTM-PD, hence new therapies are urgently required. Disrupting bacterial iron uptake pathways using gallium-protoporphyrin (IX) (GaPP), a heme analog, has been proposed as a novel antibacterial approach to tackle multi-drug resistant M. abscessus. However, the antibacterial activity of GaPP has been tested only in iron-deficient media, which cannot accurately mirror the potential activity in vivo. Herein, we investigated the potential synergistic activity between GaPP and the iron-chelating agent deferiprone (Def) in regular media against M. abscessus-infected macrophages. The safety of the treatment was assessed in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in Nuli-1 and THP-1 cell lines. Def-GaPP had synergistic activity against M. abscessus-infected macrophages where 10 mM-12.5 mg/L of Def-GaPP reduced the viability by up to 0.9 log. Furthermore, Def-GaPP showed no cytotoxicity to Nuli-1 and THP-1 cell lines at the effective antibacterial concentrations (10 mM-12.5 mg/L) of Def- GaPP. These data encourage future investigation of Def-GaPP as a novel antimicrobial against NTM-PD.
非结核分枝杆菌肺病（NTM-PD）由脓肿分枝杆菌引起，是囊性纤维化（CF）患者的常见并发症，随着时间的推移会导致肺功能恶化。目前，NTM-PD 尚无治愈方法，因此急需新的治疗方法。使用胆绿素原（IX）（GaPP），一种血红素类似物，破坏细菌铁摄取途径，已被提议作为一种新的抗菌方法来解决多药耐药脓肿分枝杆菌。然而，GaPP 的抗菌活性仅在缺铁培养基中进行了测试，这不能准确反映其在体内的潜在活性。在此，我们研究了 GaPP 与铁螯合剂地拉罗司（Def）在常规培养基中针对感染巨噬细胞的脓肿分枝杆菌的潜在协同活性。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法在 Nuli-1 和 THP-1 细胞系中评估了治疗的安全性。Def-GaPP 对感染巨噬细胞的脓肿分枝杆菌具有协同活性，其中 10 mM-12.5 mg/L 的 Def-GaPP 可将活力降低多达 0.9 对数级。此外，在 Def-GaPP 的有效抗菌浓度（10 mM-12.5 mg/L）下，Def-GaPP 对 Nuli-1 和 THP-1 细胞系均无细胞毒性。这些数据鼓励进一步研究 Def-GaPP 作为一种针对 NTM-PD 的新型抗菌药物。
