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Mutation on lysX from Mycobacterium avium hominissuis impacts the host-pathogen interaction and virulence phenotype.
Virulence ( IF 5.5 ) Pub Date : 2020-01-29 , DOI: 10.1080/21505594.2020.1713690
Greana Kirubakar 1 , Hubert Schäfer 1 , Volker Rickerts 1 , Carsten Schwarz 2 , Astrid Lewin 1
Affiliation  

The lysX gene from Mycobacterium avium hominissuis (MAH) is not only involved in cationic antimicrobial resistance but also regulates metabolic activity. An MAH lysX deficient mutant was shown to exhibit a metabolic shift at the extracellular state preadapting the bacteria to the conditions inside host-cells. It further showed stronger growth in human monocytes. In the present study, the LysX activity on host-pathogen interactions were analyzed. The lysX mutant from MAH proved to be more sensitive toward host-mediated stresses such as reactive oxygen species. Further, the lysX mutant exhibited increased inflammatory response in PBMC and multinucleated giant cell (MGC) formation in human macrophages during infection studies. Coincidentally, the lysX mutant strain revealed to be more reproductive in the Galleria mellonella infection model. Together, these data demonstrate that LysX plays a role in regulating the bacillary load in host organisms and the lack of lysX gene facilitates MAH adaptation to intracellular host-habitat, thereby suggesting an essential role of LysX in the modulation of host-pathogen interaction.

中文翻译:


鸟分枝杆菌 lysX 突变影响宿主-病原体相互作用和毒力表型。



来自人型分枝杆菌 (MAH) 的 lysX 基因不仅参与阳离子抗菌药物耐药性,而且还调节代谢活性。 MAH lysX 缺陷突变体在细胞外状态下表现出代谢转变,使细菌预先适应宿主细胞内的条件。它进一步显示人类单核细胞的生长更强。在本研究中,分析了 LysX 活性对宿主-病原体相互作用的影响。 MAH 的 lysX 突变体被证明对宿主介导的应激(例如活性氧)更敏感。此外,在感染研究期间,lysX 突变体表现出 PBMC 中炎症反应的增加和人类巨噬细胞中多核巨细胞 (MGC) 形成的增加。巧合的是,lysX 突变株在大蜡螟感染模型中具有更强的繁殖能力。总之,这些数据表明 LysX 在调节宿主生物体中的细菌负荷中发挥作用,并且 lysX 基因的缺乏促进 MAH 适应细胞内宿主栖息地,从而表明 LysX 在调节宿主-病原体相互作用中发挥重要作用。
更新日期:2020-04-20
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