Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus
Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus
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DOI：
10.1128/aac.00331-15
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发表时间：
2015-08-01
影响因子：
4.9
通讯作者：
Britigan, Bradley E.
中科院分区：
文献类型：
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作者：
Abdalla, Maher Y.;Switzer, Barbara L.;Britigan, Bradley E.
快速生长的非结核性分枝杆菌分支杆菌最近成为囊性纤维化（CF）患者的重要病原体。治疗选择是有限的，因为有机体的先天性耐药性标准抗结核抗生素，以及其他目前可用的抗生素。新的抗生素治疗M。迫切需要脓肿。本研究的目的是评估不同Ga化合物对美国典型培养物保藏中心（ATCC）菌株和M.从CF和其他患者获得的积液。在我们的结果中，使用Ga（NO3）和所有其它测试的Ga化合物抑制ATCC 19977和M的临床分离株的生长。你好抑制介导的干扰铁的吸收，作为额外的外源性铁（Fe）恢复基础生长。对于相同的Ga螯合物，分离株之间的抑制作用存在适度差异，并且对于大多数Ga螯合物，与Ga（NO3）（3）的效力仅存在轻微差异。与此相反，Ga-原卟啉完全和显着抑制ATCC菌株和临床分离的M。浓度远低于Ga（NO3）（3）的脓肿。在体外肉汤培养中，Ga-原卟啉比Ga（NO3）（3）更有效。当M.评估了人巨噬细胞THP-1细胞系内的肿瘤生长。Ga-原卟啉的活性比Ga（NO）2高>20倍。目前的工作表明，Ga对ATCC菌株以及耐药性临床分离的M.包括高度抗真菌的菌株MC 2638。基于镓的治疗提供了进一步发展的潜力，作为一种新的治疗M。你好
The rapidly growing nontuberculous mycobacterial species Mycobacterium abscessus has recently emerged as an important pathogen in patients with cystic fibrosis (CF). Treatment options are limited because of the organism's innate resistance to standard antituberculotts antibiotics, as well as other currently available antibiotics. New antibiotic approaches to the treatment of M. abscessus are urgently needed. The goal of the present study was to assess the growth-inhibitory activity of different Ga compounds against an American Type Culture Collection (ATCC) strain and clinical isolates of M. abscessus obtained from CF and other patients. In our results, using Ga(NO,), and all of the other Ga compounds tested inhibited the growth of ATCC 19977 and clinical isolates of M. abscessus. Inhibition was mediated by disrupting iron uptake, as the addition of exogenous iron (Fe) restored basal growth. There were modest differences in inhibition among the isolates for the same Ga chelates, and for most Ga chelates there was only a slight difference in potency from Ga(NO3)(3). In contrast, Ga-protoporphyrin completely and significantly inhibited the ATCC strain and clinical isolates of M. abscessus at much lower concentrations than Ga(NO3)(3). In in vitro broth culture, Ga-protoporphyrin was more potent than Ga(NO3)(3). When M. abscessus growth inside the human macrophage THP-1 cell line was assessed, Ga-protoporphyrin was >20 times more active than Ga(NO,),. The present work suggests that Ga exhibits potent growth-inhibitory capacity against the ATCC strain, as well as against antibiotic-resistant clinical isolates of M. abscessus, including the highly antibiotic-resistant strain MC2638. Ga-based therapy offers the potential for further development as a novel therapy against M. abscessus.