Gupta Amita
Department of Microbiology, University of Delhi South Campus, New Delhi, India.
FEMS Microbiol Lett. 2009 Jan;290(1):45-53. doi: 10.1111/j.1574-6968.2008.01400.x. Epub 2008 Nov 10.
Toxin-antitoxin (TA) loci are typically two-component systems that encode a stable toxin, which binds an essential host target leading to cell growth arrest and/or cell death, and an unstable antitoxin, which prevents the cytotoxic activity of the toxin. The ubiquitous presence of these loci in bacterial genomes, along with their demonstrated toxicity not only in the native but also in heterologous systems, has provided the possibility of their use in wide-spectrum antibacterials. Mycobacterium tuberculosis contains nearly 40 TA loci, most of which are yet to be characterized. Here we report the heterologous toxicity of these TA loci in Escherichia coli and show that only a few of the M. tuberculosis-encoded toxins can inhibit E. coli growth and have a killing effect. This killing effect can be suppressed by coexpression of the cognate antitoxin. This work has identified functional TA pairs for sequences that are presently unannotated in the mycobacterial genome. These toxins need to be further tested for their activity in the native host and other organism backgrounds and growth environments for utilization of their antibacterial potential.
毒素-抗毒素（TA）位点通常是双组分系统，编码一种稳定的毒素，该毒素结合宿主必需靶点导致细胞生长停滞和/或细胞死亡，以及一种不稳定的抗毒素，其可阻止毒素的细胞毒性活性。这些位点在细菌基因组中普遍存在，并且它们不仅在天然系统中，而且在异源系统中都表现出毒性，这为它们用于广谱抗菌剂提供了可能性。结核分枝杆菌含有近40个TA位点，其中大部分尚未被表征。在这里我们报告了这些TA位点在大肠杆菌中的异源毒性，并表明只有少数结核分枝杆菌编码的毒素能够抑制大肠杆菌生长并具有杀伤作用，可以通过共表达同源抗毒素来抑制这种杀伤作用。这项工作已经鉴定出了在分枝杆菌基因组中目前未注释的序列的功能性TA对。需进一步测试这些毒素在天然宿主以及其他生物体背景和生长环境中的活性，以利用它们的抗菌潜力。
