Mycobacterium tuberculosis RNA expression patterns in sputum bacteria indicate secreted Esx factors contributing to growth are highly expressed in active disease
Mycobacterium tuberculosis RNA expression patterns in sputum bacteria indicate secreted Esx factors contributing to growth are highly expressed in active disease
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DOI：
10.3389/fmicb.2011.00266
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发表时间：
2012-01-01
影响因子：
5.2
通讯作者：
Graham, James E.
中科院分区：
文献类型：
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作者：
Bukka, Archana;Price, Christopher T. D.;Graham, James E.
为了确定在活动性感染期间结核杆菌在肺部生长的能力的因素，我们分析了患者痰中细菌的RNA表达模式。在鉴定的细菌转录本中，最突出的是那些编码Esat-6亚家族分泌肽的转录本，包括EsxK和EsxL(Rv1197和Rv1198)。H37Rv esxKL和esxJI转录本在不同的生长条件下差异表达，这些基因的中断改变了典型实验室分批培养物的生长期动力学。这些生长缺陷，包括Delta esxKL突变体在原代人巨噬细胞中的细胞内生长减少，可以通过低复数联合感染或与野生型细菌共同培养而逆转，证明了分泌因子拯救同基因突变的能力。仅补充esxL或单独补充esx1(Rv1198或Rv1037c)也可以减少观察到的生长缺陷，表明这些基因编码能够促进生长的因子。我们的研究表明，结核分枝杆菌Mtb9.9家族分泌因子EsxL和Esx1可以反式调节细胞内细菌的生长，并在活动性肺部感染中高表达。
To identify factors contributing to the ability of tubercle bacilli to grow in the lung during active infection, we analyzed RNA expression patterns in bacteria present in patient sputum. Prominent among bacterial transcripts identified were those encoding secreted peptides of the Esat-6 subfamily that includes EsxK and EsxL (Rv1197 and Rv1198). H37Rv esxKL and esxJI transcripts were differentially expressed under different growth conditions, and disruption of these genes altered growth phase kinetics in typical laboratory batch broth cultures. These growth defects, including the reduced intracellular growth of an Delta esxKL mutant in primary human macrophages, were reversed by either low multiplicity co-infection or co-culture with wild-type bacteria, demonstrating the ability of the secreted factors to rescue isogenic mutants. Complementing either only esxL or esxl alone (Rv1198 or Rv1037c) also reduced observed growth defects, indicating these genes encode factors capable of contributing to growth. Our studies indicate that the Mycobacterium tuberculosis Mtb9.9 family secreted factors EsxL and Esxl can act in trans to modulate growth of intracellular bacteria, and are highly expressed during active human lung infection.