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印度南部肺外淋巴结结核分枝杆菌菌株多样性的最新趋势及其与耐药性和宿主免疫反应的关联。

The recent trend in mycobacterial strain diversity among extra pulmonary lymph node tuberculosis and their association with drug resistance and the host immunological response in South India.

作者信息

Sivakumar Shanmugam, Chandramohan Yuvaraj, Kathamuthu Gokul Raj, Sekar Gomathi, Kandhasamy Devika, Padmanaban Venkatesan, Hissar Syed, Tripathy Srikanth P, Bethunaickan Ramalingam, Dhanaraj Baskaran, Babu Subash, Ranganathan Uma Devi

机构信息

Department of Bacteriology, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.

Department of Immunology, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.

出版信息

BMC Infect Dis. 2020 Nov 26;20(1):894. doi: 10.1186/s12879-020-05597-0.

Abstract

BACKGROUND

Tuberculosis (TB) though primarily affects the lungs it may also affect the other parts of the body and referred as extra pulmonary (EPTB). This study is focused on understanding the genetic diversity and molecular epidemiology of Mycobacterium tuberculosis (M.tb) among tuberculous lymphadenitis (TBL), a form of EPTB patients identified in Chennai, Tamil Nadu.

METHODS

The genetic diversity was identified by performing spoligotyping on the M.tb clinical isolates that were recovered from lymph node samples. A total of 71 M.tb isolates were recovered from extra pulmonary lymph node samples and subjected to Drug susceptibility testing and spoligotyping was carried out. In addition, immunological characterization from blood of same individuals from whom M.tb was isolated was carried out between the two major lineages groups East African Indian 3 (EAI3) and non-EAI3 strains by ELISA. The results of spoligotyping patterns were compared with the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4).

RESULTS

We found 41 spoligotype patterns and their associated lineages. Out of 41 spoligotype pattern, only 22 patterns are available in the spoldB4 database with Spoligotype international Type (SIT) number and remaining patterns were orphan strains without SIT number. The most predominant spoligotype lineage that was found in lymph node sample in this region of India was EAI (36), followed by central Asian strain (CAS) (6), T1 (5), Beijing (3), Latin American & Mediterranean (LAM) (2), U (1), X2 (1) and orphan (22). In addition to EAI, CAS and Beijing, our study identified the presence of orphan and unique spoligotyping patterns in Chennai region. We observed six drug resistant isolates. Out of six drug resistant isolates, four were resistant to isoniazid drug and associated with EAI family. Moreover, we observed increased levels of type 2 and type 17 cytokine profiles between EAI3 and non-EAI family, infected individuals.

CONCLUSIONS

The study confirms that EAI lineage to be the most predominant lineages in EPTB patients with lymphadenitis and were found to have increased type 1 and type 17 proinflammatory cytokine profiles.

摘要

背景

结核病(TB)虽然主要影响肺部,但也可能影响身体的其他部位,被称为肺外结核(EPTB)。本研究的重点是了解在印度泰米尔纳德邦金奈确诊的肺外结核患者的一种形式——结核性淋巴结炎(TBL)中结核分枝杆菌(M.tb)的遗传多样性和分子流行病学。

方法

通过对从淋巴结样本中分离出的M.tb临床分离株进行间隔寡核苷酸分型(spoligotyping)来确定遗传多样性。总共从肺外淋巴结样本中分离出71株M.tb分离株,并进行药敏试验和间隔寡核苷酸分型。此外,通过酶联免疫吸附测定(ELISA)对分离出M.tb的同一个体的血液进行免疫特征分析,比较东非印度3型(EAI3)和非EAI3菌株这两个主要谱系组之间的情况。将间隔寡核苷酸分型模式的结果与瓜德罗普岛巴斯德研究所的世界间隔寡核苷酸分型数据库(SpolDB4)进行比较。

结果

我们发现了41种间隔寡核苷酸分型模式及其相关谱系。在41种间隔寡核苷酸分型模式中,只有22种模式在SpolDB4数据库中有间隔寡核苷酸分型国际类型(SIT)编号,其余模式为无SIT编号的孤儿菌株。在印度该地区的淋巴结样本中发现的最主要的间隔寡核苷酸分型谱系是EAI(36),其次是中亚菌株(CAS)(6)、T1(5)、北京型(Beijing)(3)、拉丁美洲和地中海型(LAM)(2)、U型(1)、X2型(1)和孤儿菌株(22)。除了EAI、CAS和北京型,我们的研究还在金奈地区发现了孤儿菌株和独特的间隔寡核苷酸分型模式。我们观察到6株耐药分离株。在6株耐药分离株中,4株对异烟肼耐药,且与EAI家族相关。此外,我们观察到EAI3和非EAI家族感染个体之间的2型和17型细胞因子水平升高。

结论

该研究证实EAI谱系是患有淋巴结炎的EPTB患者中最主要的谱系,并且发现其1型和17型促炎细胞因子水平升高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b6/7690019/0d875ebcbe97/12879_2020_5597_Fig1_HTML.jpg

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