ESAT-6 Secretion-Independent Impact of ESX-1 Genes espF and espG1 on Virulence of Mycobacterium tuberculosis

ESAT-6 Secretion-Independent Impact of ESX-1 Genes espF and espG1 on Virulence of Mycobacterium tuberculosis
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DOI:
10.1093/infdis/jiq089
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发表时间:
2011-04-15
影响因子:
6.4
通讯作者:
Brosch, Roland
Brosch, Roland
中科院分区:
医学2区
文献类型:
--
作者:
Bottai, Daria;Majlessi, Laleh;Brosch, Roland

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方法。为了阐明EspF/G(1)的作用,我们构建了3个结核分枝杆菌敲除菌株,其中EspF、espG(1)或卡介苗(bcg)和微分枝杆菌的RD1(bcg)-RD1(mic)区对应的片段也含有EspF和espG(1)。据报道,EspF/G(1)在海洋分枝杆菌和垢垢分枝杆菌中的同源物参与EsxA/B的分泌。对这些菌株的分析表明,与模式生物耻毛分枝杆菌或海洋分枝杆菌的观察结果不同,结核分枝杆菌中espF和espG(1)的破坏不会影响EsxA/B的分泌和T细胞识别,但仍会引起严重的减弱。两种ESX-1相关表型(即EsxA/B分泌和毒力)的分离表明,EsxA/B分泌并不是ESX-1系统功能的唯一指标,并表明涉及EspF/G(1)的其他过程也在ESX-1介导的致病性中发挥重要作用。
Methods. To elucidate the role of EspF/G(1), whose orthologs in Mycobacterium marinum and Mycobacterium smegmatis are reportedly involved in EsxA/B secretion, we constructed 3 M. tuberculosis knockout strains deleted for espF, espG(1) or the segment corresponding to the combined RD1(bcg)-RD1(mic) region of bacille Calmette-Guerin (BCG) and Mycobacterium microti, which also contains espF and espG(1).Results. Analysis of these strains revealed that, unlike observations with the model organisms M. smegmatis or M. marinum, disruption of espF and espG(1) in M. tuberculosis did not impact the secretion and T cell recognition of EsxA/B but still caused severe attenuation.Conclusions. The separation of the 2 ESX-1-connected phenotypes (ie, EsxA/B secretion and virulence) indicates that EsxA/B secretion is not the only readout for a functional ESX-1 system and suggests that other processes involving EspF/G(1) also play important roles in ESX-1-mediated pathogenicity.