New directions using reporter enzyme fluorescence (REF) as a tuberculosis diagnostic platform.

New directions using reporter enzyme fluorescence (REF) as a tuberculosis diagnostic platform.
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DOI:
10.1016/j.tube.2016.09.009
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发表时间:
2016-12
期刊:
Tuberculosis (Edinburgh, Scotland)
影响因子:
--
通讯作者:
Cirillo JD
Cirillo JD
中科院分区:
其他
文献类型:
--
作者:
Sule P;Tilvawala R;Behinaein P;Walkup GK;Cirillo JD

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虽然结核病(TB)是世界范围内人类发病和死亡的最常见原因之一,诊断方法已经存在了100多年,但诊断仍然是一个挑战。诊断的主要问题与获得明确结果所需的时间、获取痰液的困难、所用的主要临床材料以及病原体结核分枝杆菌在体内几乎任何组织中引起疾病的能力有关。为了降低结核病的发病率,需要发现新的干预措施,因为目前的技术只能控制感染人数,而不能减少感染人数。诊断创新尤为必要,因为目前还没有有效的儿科或肺外结核诊断方法,而且只有不到25%的被认为患有结核病的患者发现了多重耐药。全球最常见的诊断方法仍然是痰抗酸染色,其阈值约为10,000个细菌/ml,仅在出现症状后约5-6个月才能达到。为了在疾病过程中更早地获得明确的诊断结果,我们开发了一种诊断方法,称为报告酶荧光(REF),该方法利用M.结核病和定制底物可在临床样本中产生低至10个细菌/ml的特异性荧光信号。我们相信,REF技术的独特生物学特性将使其能够提供新的诊断信息,这些信息将补充所有现有的诊断测试以及目前已知正在开发的诊断测试。
Although tuberculosis (TB) is one of the most common causes of morbidity and mortality in humans worldwide and diagnostic methods have been in place for more than 100 years, diagnosis remains a challenge. The main problems with diagnosis relate to the time needed to obtain a definitive result, difficulty in obtaining sputum, the primary clinical material used, and the ability of the causative agent, Mycobacterium tuberculosis, to cause disease in nearly any tissue within the body. In order to decrease incidence of TB, discovery of a novel interventions will be required, since current technologies have only been able to control numbers of infections, not reduce them. Diagnostic innovation is particularly needed because there are no effective pediatric or extrapulmonary TB diagnostic methods and multiple-drug resistance is only identified in less than 25% of those patients that are thought to have it. The most common diagnostic method worldwide remains acid-fast stain on sputum, with a threshold of ~10,000 bacteria/ml that is only reached ~5–6 months after development of symptoms. In order to obtain definitive diagnostic results earlier during the disease process, we have developed a diagnostic method designated reporter enzyme fluorescence (REF) that utilizes BlaC produced by M. tuberculosis and custom substrates to produce a specific fluorescent signal with as few as 10 bacteria/ml in clinical samples. We believe that the unique biology of the REF technique will allow it to contribute new diagnostic information that is complementary to all existing diagnostic tests as well as those currently known to be in development.
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