关键词: Chemotherapeutic efficacy Mycobacterium intracellulare Neutrophil Nontuberculous mycobacteria Virulence

Mesh : Mice Animals Mycobacterium avium Complex / genetics Mycobacterium avium-intracellulare Infection / microbiology Virulence Mice, Inbred C57BL Lung / microbiology Pneumonia Inflammation Patient Acuity

来  源:   DOI:10.1186/s12866-023-02831-y

Abstract:
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.
摘要:
背景:胞内分枝杆菌是鸟分枝杆菌-胞内肺病(MAC-PD)的主要病原体。然而,胞内分枝杆菌的毒力特征和体内化疗疗效尚不清楚。在这项研究中,我们在C57BL/6小鼠中检测了9种具有不同临床表型和基因型的胞内分枝杆菌菌株的毒力。
结果:我们将三种类型的毒力表型(高,中间,和低)基于细菌负荷的动力学,组织学肺部炎症,和嗜中性粒细胞浸润。高毒力菌株在肺中的嗜中性粒细胞浸润比中、低毒力菌株更严重,支气管肺泡灌洗液中中性粒细胞平均百分比的6.27倍和11.0倍差异,分别。特别是,高毒力菌株M.i.198在小鼠中显示出最高的死亡率,这与临床疾病的快速进展相对应。在感染药物敏感性高毒力菌株M019的小鼠中,含克拉霉素的化疗显示出最高的疗效。利福平的单一疗法会加剧肺部炎症,并增加淋巴细胞和嗜中性粒细胞浸润。
结论:胞内分枝杆菌临床菌株的毒力表型多样,高毒力菌株与感染小鼠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。
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