Katiyar Amit, Singh Harpreet, Azad Krishna Kant
ICMR-AIIMS Computational Genomics Centre, Indian Council of Medical Research, Ansari Nagar, New Delhi-110029, India.
Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
J Integr Bioinform. 2018 Jul 3;15(3):/j/jib.2018.15.issue-3/jib-2017-0041/jib-2017-0041.xml. doi: 10.1515/jib-2017-0041.
Metabolic adaptation to the host environment has been recognized as an essential mechanism of pathogenicity and the growth of Mycobacterium tuberculosis (Mtb) in the lungs for decades. The Mtb uses CO2 as a source of carbon during the dormant or non-replicative state. However, there is a lack of biochemical knowledge of its metabolic networks. In this study, we investigated the CO2 fixation pathways (such as ko00710 and ko00720) most likely involved in the energy production and conversion of CO2 in Mtb. Extensive pathway evaluation of 23 completely sequenced strains of Mtb confirmed the existence of a complete list of genes encoding the relevant enzymes of the reductive tricarboxylic acid (rTCA) cycle. This provides the evidence that an rTCA cycle may function to fix CO2 in this bacterium. We also proposed that as CO2 is plentiful in the lungs, inhibition of CO2 fixation pathways (by targeting the relevant CO2 fixation enzymes) could be used in the expansion of new drugs against the dormant Mtb. In support of the suggested hypothesis, the CO2 fixation enzymes were confirmed as a potential drug target by analyzing a number of attributes necessary to be a good bacterial target.
几十年来，对宿主环境的代谢适应已被认为是结核分枝杆菌（Mtb）致病性和在肺部生长的一种重要机制。在休眠或非复制状态下，Mtb利用二氧化碳作为碳源。然而，目前缺乏对其代谢网络的生化知识。在本研究中，我们调查了最有可能参与Mtb中二氧化碳能量产生和转化的二氧化碳固定途径（如ko00710和ko00720）。对23株全基因组测序的Mtb菌株进行广泛的途径评估，证实了存在一整套编码还原性三羧酸（rTCA）循环相关酶的基因。这提供了证据表明rTCA循环可能在该细菌中发挥固定二氧化碳的作用。我们还提出，由于肺部二氧化碳丰富，抑制二氧化碳固定途径（通过靶向相关的二氧化碳固定酶）可用于开发针对休眠Mtb的新药。为支持所提出的假设，通过分析成为良好细菌靶点所需的一些属性，证实二氧化碳固定酶是一种潜在的药物靶点。
