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在活化的巨噬细胞内,一种流行的耐多药结核分枝杆菌菌株及其非优势变体的存活。

Survival of an epidemic MDR strain of Mycobacterium tuberculosis and its non-prosperous variant within activated macrophages.

机构信息

Instituto de Medicina Experimental (IMEX)-CONICET-Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, C1425FQB Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290, C1425FQB Buenos Aires, Argentina; Instituto Nacional de Enfermedades Infecciosas (INEI), ANLIS "Carlos G. Malbrán", Vélez Sarsfield 563, C1282AFF Buenos Aires, Argentina.

出版信息

Infect Genet Evol. 2019 Sep;73:248-254. doi: 10.1016/j.meegid.2019.05.005. Epub 2019 May 8.

Abstract

The fitness of a pathogen results from the interaction of multiple factors favoring either epidemiological success or failure. Herein, we studied the performance of the M strain, a highly successful multidrug resistant Mycobacterium tuberculosis genotype, and its non-prosperous variant, the 410 strain, in activated human monocyte-derived macrophages. Both strains showed comparable ability to induce necrotic cell death and to survive in apoptotic macrophages. Of the various macrophage activation conditions tested, none led to an enhanced control of the outbreak strain. The combination of 1,25(OH) vitaminD3 and IFN-γ favored significantly the control of the non-prosperous 410 strain. These observations indicate that the ability of the M strain to survive within the hostile intracellular milieu is conserved, and the overall fitness cost paid by this genotype would be low. Our results provide additional evidence on bacterial traits that may have contributed to the epidemiological success of the M strain.

摘要

病原体的适应性源于多种因素的相互作用,这些因素有利于其在流行病学上的成功或失败。在此,我们研究了高度成功的多药耐药结核分枝杆菌基因型 M 株及其非优势变体 410 株在激活的人单核细胞衍生的巨噬细胞中的表现。这两种菌株都具有诱导坏死性细胞死亡和在凋亡巨噬细胞中存活的能力。在所测试的各种巨噬细胞激活条件中,没有一种条件能显著增强对流行株的控制。1,25(OH)2D3 和 IFN-γ 的组合显著有利于控制非优势 410 株。这些观察结果表明,M 株在恶劣的细胞内环境中生存的能力是保守的,这种基因型所付出的整体适应性代价是低的。我们的研究结果提供了更多关于可能有助于 M 株在流行病学上成功的细菌特征的证据。

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