Department of Bacteriology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachi-Dori, Chuo-Ku, Niigata, 951-8510, Japan.
Tokushima Prefecture Naruto Hospital, Tokushima, Japan.
BMC Microbiol. 2023 Apr 3;23(1):94. doi: 10.1186/s12866-023-02831-y.
Mycobacterium intracellulare is a major etiological agent of Mycobacterium avium-intracellulare pulmonary disease (MAC-PD). However, the characteristics of the virulence of M. intracellulare and the in vivo chemotherapeutic efficacy remain unclear. In this study, we examined the virulence of nine M. intracellulare strains with different clinical phenotypes and genotypes in C57BL/6 mice.
We classified three types of virulence phenotypes (high, intermediate, and low) based on the kinetics of the bacterial load, histological lung inflammation, and neutrophilic infiltration. High virulence strains showed more severe neutrophilic infiltration in the lungs than intermediate and low virulence strains, with 6.27-fold and 11.0-fold differences of the average percentage of neutrophils in bronchoalveolar lavage fluid, respectively. In particular, the high virulence strain M.i.198 showed the highest mortality in mice, which corresponded to the rapid progression of clinical disease. In mice infected with the drug-sensitive high virulence strain M019, clarithromycin-containing chemotherapy showed the highest efficacy. Monotherapy with rifampicin exacerbated lung inflammation with increased lymphocytic and neutrophilic infiltration into the lungs.
The virulence phenotypes of clinical strains of M. intracellulare were diverse, with high virulence strains being associated with neutrophilic infiltration and disease progression in infected mice. These high virulence strains were proposed as a useful subject for in vivo chemotherapeutic experiments.
胞内分枝杆菌是鸟分枝杆菌胞内复合体肺病（MAC-PD）的主要病因。然而，胞内分枝杆菌的毒力特征和体内化学治疗效果尚不清楚。在这项研究中，我们检查了 9 株具有不同临床表型和基因型的胞内分枝杆菌菌株在 C57BL/6 小鼠中的毒力。
我们根据细菌负荷、组织学肺炎症和嗜中性粒细胞浸润的动力学将三种毒力表型（高、中、低）进行分类。高毒力菌株在肺部引起更严重的嗜中性粒细胞浸润，与中、低毒力菌株相比，支气管肺泡灌洗液中嗜中性粒细胞的平均百分比分别高出 6.27 倍和 11.0 倍。特别是高毒力菌株 M.i.198 在小鼠中表现出最高的死亡率，这与临床疾病的快速进展相对应。在感染敏感高毒力菌株 M019 的小鼠中，含克拉霉素的化疗显示出最高的疗效。利福平单药治疗加剧了肺炎症，导致肺部淋巴细胞和嗜中性粒细胞浸润增加。
胞内分枝杆菌临床株的毒力表型多种多样，高毒力菌株与感染小鼠中的嗜中性粒细胞浸润和疾病进展有关。这些高毒力菌株被提议作为体内化学治疗实验的有用对象。
