滚环扩增技术直接检测痰标本中结核分枝杆菌利福平敏感性的初步研究

目的评价滚环扩增技术（rolling circle amplification，RCA）对痰标本中结核分枝杆菌利福平敏感性的直接快速检测效果。方法选取首都医科大学附属北京胸科医院住院的初治和复治涂阳肺结核患者24h痰标本32份，采用RCA法、直接测序法及传统药敏试验绝对浓度法测定痰标本中结核分枝杆菌对利福平的敏感性，并进行了比较。结果32份痰标本中结核分枝杆菌，采用RCA法24株可检测到rpoB基因突变，其中23株单位点突变（516位2株，526位12株，531位9株），l株516位和526位联合突变，与直接测序结果均一致。32份痰标本的RCA方法检测与DNA测序结果和药物敏感性试验进行对比，28株结果均一致。4株结果不一致，其中2株RCA及测序无突变，药敏结果显示为耐药；2株RCA及测序显示有突变，药敏结果显示为敏感。结论RCA法用于痰标本中直接检测结核分枝杆菌对利福平的敏感性，同直接测序法结果一致，同传统药敏试验相比，RCA法能够大幅度节省时间，具有很好的临床应用和推广前景。

人类免疫缺陷病毒合并结核分枝杆菌感染者的抗结核细胞免疫功能

目的评价HIV合并结核分枝杆菌潜伏感染或合并活动性结核患者的抗结核细胞免疫功能。方法应用早期分泌性抗原靶蛋白（ESAT）-6和培养滤出蛋白（CFP）-10诱导的结核酶联免疫斑点法对云南地区100例明确诊断的HIV感染者的血液标本进行结核分枝杆菌特异性T淋巴细胞检测，同时应用流式细胞仪检测外周血CD3-CD4-T淋巴细胞和CD3^＋CD8^＋T淋巴细胞的绝对计数水平。采用Mann-Whitney检验进行非参数统计分析。结果临床上无活动性结核感染证据的HIV感染者中合并结核分枝杆菌潜伏感染的感染率高达67．6％。HIV合并结核分枝杆菌潜伏感染者的外周血CD3-CD4-T淋巴细胞（532×10^6／L）和CD3-CD8-T淋巴细胞（473×10^6／L）绝对计数与单纯HIV感染者（406×10^6／L和504×10^6／L）相比，差异无统计学意义。HIV合并活动性结核感染者的外周血CD3^＋CD4^＋ T淋巴细胞绝对计数平均值为189×10^6／L，CD3^＋CD8^T淋巴细胞绝对计数平均值为293×10^6／L，均显著低于单纯HIV合并结核潜伏感染组和HIV组（=168．0，U=163．0；U=147．0，U=374．0；均P〈0．01）。HIV合并活动性结核感染者的ESAT-6和CFP-10抗原特异性斑点形成细胞数（31／10^6细胞和82／10^6细胞）显著低于HIV合并结核分枝杆菌潜伏感染者（92／10^6细胞和109／10^6细胞，U=507．0．U=529．5，均P〈0．01）。结论我国无活动性结核临床证据的HIV感染人群中有较高的结核潜伏感染率。HIV合并活动性结核感染者的总体细胞免疫应答功能及特异性抗结核免疫应答功能均严重受损。

958例结核病患者临床分离株耐药基因检测结果分析

目的分析958例患者结核分枝杆菌的相关基因突变位点。方法收集2017年1-12月西安市胸科医院对痰液、组织、胸腹腔积液等各类型临床标本进行分枝杆菌培养阳性的2718例患者的菌液,经菌种鉴定非结核分枝杆菌感染患者-11例.结核分枝杆菌感染患者2677例.选择结核分枝杆菌菌种同时进行MGIT 960液体药物敏感性试验(简称“药敏试验”)和耐药基因检测的患者958例.分析不同性别、年龄组患苕的结核分枝杆菌菌株间突变位点差异及突变位点与表型药敏试验检测结果的符合率。计数资料采用x^2检验,以PV0.05为差异有统计学意义。结果958例患者菌株的基因突变位点分析中,任一位点突变率为19.52%( 187/958).5~、21~、41~、61~83岁各年龄组的菌株mpB基因位点突变率分别为7. 89%(9 114) J3. 52%(63/466)、18. 27%(38/208)和9.41;(16 170)。不同年龄组中.中年组的mpB基因位点突变率与青少年组和老年组比较差异有统计学意义(x^2值分别为6.358和5.994. P值分别为0.013和0.018);男性任一位点突变率为19. 45%(121 622).女性为19. 05%(61 336),不同性别比较差异无统计学意义(x^2=0. 023.P=0. 932);突变位点与表型药敏试验的符合率以利福平 ropB 531(C-T)(96. 10%,74/77)、异烟肼 katG 315(6-0(98. 45%, 127/129)最高.但 ropB 51KT-C)与利福平表型药敏试验结果相符率较差(0.00%.0/10)。结论不同年龄组患者的菌株基因位点突变率差异有统计学意义.中年组突变率最高;不同性别患者的突变率差异无统计学意义;应当结合表型药敏试验的检测结果进行耐药基因位点突变在诊断意义上的分析。

Differentiation of Crohn’s disease from intestinal tuberculosis in India in 2010

Differentiating intestinal tuberculosis from Crohn’s disease (CD) is an important clinical challenge of considerable therapeutic significance. The problem is of greatest magnitude in countries where tuberculosis continues to be highly prevalent, and where the incidence of CD is increasing. The final clinical diagnosis is based on a combination of the clinical history with endoscopic studies, culture and polymerase chain reaction for Mycobacterium tuberculosis, biopsy pathology, radiological investigations and response to therapy. In a subset of patients, surgery is required and intraoperative findings with pathological study of the resected bowel provide a definitive diagnosis. Awareness of the parameters useful in distinguishing these two disorders in each of the different diagnostic modalities is crucial to accurate decision making. Newer techniques, such as capsule endoscopy, small bowel enteroscopy and immunological assays for Mycobacterium tuberculosis, have a role to play in the differentiation of intestinal tuberculosis and CD. This review presents currently available evidence regarding the usefulness and limitations of all these different modalities available for the evaluation of these two disorders.

Thalidomide induces mucosal healing in Crohn's disease: Case report

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximabafter three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis

AIM:To investigate the utility of immunohistochemical(IHC) staining with an antibody to Mycobacterium tuberculosis(M.tuberculosis) for the diagnosis of intestinal tuberculosis(TB).METHODS:We retrospectively identified 10 patients(4 males and 6 females;mean age = 65.1 ± 13.6 years) with intestinal TB.Clinical characteristics,including age,gender,underlying disease,and symptoms were obtained.Chest radiograph and laboratory tests,including sputum Ziehl-Neelsen(ZN) staining,M.tuberculosis culture,and sputum polymerase chain reaction(PCR) for tubercle bacilli DNA,as well as Tuberculin skin test(TST) and QuantiFERON-TB gold test(QFT),were examined.Colonoscopic records recorded on the basis of Sato's classification were also reviewed,in addition to data from intestinal biopsies examined for histopathological findings,including hematoxylin and eosin staining,and ZN staining,as well as M.tuberculosis culture,and PCR for tubercle bacilli DNA.For the present study,archived formalin-fixed paraffin-embedded(FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M.tuberculosis complex.These sections were also stained with the pan-macrophage marker CD68 antibody.RESULTS:From the clinical data,we found that no patients were immunocompromised,and that the main symptoms were diarrhea and weight loss.Three patients displayed active pulmonary TB,six patients(60%) had a positive TST,and 4 patients(40%) had a positive QFT.Colonoscopic findings revealed that all patients had type 1 findings(linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules),all of which were located in the right hemicolon and/or terminal ileum.Seven patients(70%) had concomitant healed lesions in the ileocecal area.No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples,and both M.tuberculosis culture and PCR for tubercle bacilli DNA were negative in all samples.The histopathological data revealed that tuberculous granulomas were present in 4 cases(40%).IHC staining in archived FFPE samples with anti-M.tuberculosis monoclonal antibody revealed positive findings in 4 patients(40%);the same patients in which granulomas were detected by hematoxylin and eosin staining.M.tuberculosis antigens were found to be mostly intracellular,granular in pattern,and primarily located in the CD68 + macrophages of the granulomas.CONCLUSION:IHC staining with a monoclonal antibody to M.tuberculosis may be an efficient and simple diagnostic tool in addition to classic examination methods for the diagnosis of intestinal TB.

NOD2 and ATG16L1 polymorphisms affect monocyte responses in Crohn's disease

AIM： TO assess whether polymorphisms in NOD2 and ATG16L1 affect cytokine responses and mycobacterium avium subspecies paratuberculosis （MAP） survival in monocytes from Crohn＇s disease （CD） patients METHODS： Monocytes were isolated from peripheral blood of CD patients of known genotype for common single nucleotide polymorphisms of NOD2 and ATG16L1, Monocytes were challenged with MAP and bacterial per- sistence assessed at subsequent time-points. Cytokine responses were assayed using a Milliplex multi-analyte profiling assay for 13 cytokines. RESULTS： Monooltes heterozygous for a NOD2 polymorphism （R702W, P268S, or 1007fs） were more permissive for growth of MAP （P = 0.045） than those without. There was no effect of NOD2 genotype on subsequent cytokine expression. The T300A polymorphism of ATG16L1 did not affect growth of MAP in our model （P = 0.175）, but did increase expression of cytokines interleukin （IL）-10 （P = 0.047） and IL-6 （P = 0.019）. CONCLUSION： CD-associated polymorphisms affected the eliminaUon of MAP from ex v/vo monooltes （NOD2）, or expression of certain oltokines （ATG16LI）, implying independent but contributory roles in the pathogenesis of CD.

Animal models to study Mycobacterium tuberculosis and HIV co-infection

Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.

An epidemiological study of resistant tuberculosis in Chongqing,China

Background The epidemiological characteristics of drug-resistant tuberculosis （DR-TB） is fundamental to improving the prevention and control of DR-TB. Mutations in katG315 is thought to be the most predictive molecule markers for Isoniazid （INH） resistance in Mycobacterium tuberculosis （MTB）. However, mutations to these genes have not been thoroughly studied in China, and epidemiological evidence of their expression levels are especially lacking in the southwest of China, which has a high TB burden within the population. Methods MTB isolates were obtained from patients with active pulmonary tuberculosis at the TB dispensary and Chest hospital in Chongqing city between June 2003 and June 2006. Proportion methods were used to test the sensitivity to INH, RFP, SM and EMB of cultured MTB. A total of 100 MTB isolates were also randomly selected for analysis of the molecular mutation spectrum of katG by DNA sequencing. Results Totally 1 089 MTB isolates that completed positive sputum cultures and evaluated for their sensitivity to the four first-line drugs among 2 777 patients with TB. The prevalence of DR-TB and multi-drug resistant tuberculosis （MDR-TB） were 27.7% （302/1 089） and 7.3% （79/1 089）, respectively. The resistance to anti-TB drugs was found to be highest for SM （16.3%） and INH （14.0%）. There was also a significant increase in the prevalence of resistance to RFP and EMB （P〈0.01）, and an increase in MDR-TB between June 2003 and June 2004 and between July 2005 and June 2006. The total mutation rate of katG315 was 75＂5% （37/49） in INH-resistant MTB, and mutation sites included $315T, $315N and $315I with mutation rates of 81.1% （30/37）, 13.5% （5/37） and 5.4% （2/37）, respectively No katG315 mutants were found in any of the 48 INH-sensitive MTB. Our preliminary diagnostic results suggest that mutations in katG315 may potentially serve as molecular markers that can be used to diagnose the resistance to anti-TB drug of INH. Conclusion In the Chongqing, DR-TB and MDR-TB are increasing, and are becoming key problems for tuberculosis control. The use of katG315 mutations as potential molecule markers for drug resistance to INH may help improve patient treatment and decrease the spread of the disease

Molecular Cloning of PhoR Sensor Domain from Mycobacterium tuberculosis for Structure-Based Discovery of Novel Anti-Tubercular

The emergence of multidrug-resistant strains （MDR-TB） and extensively drug-resistant strains （XDR-TB） has fuelled the quest for novel drugs and drug targets for its successful treatment. One of the potential candidates as novel TB drug target is the PhoR sensor domain, an extracellular domain of PhoR histidine kinase. PhoR sensor domain is part of the two-component system PhoR-PhoP that senses environmental stimuli and relays the signal to control the expression of 78 virulent associated genes in Mycobacterium tuberculosis. 3D structure of the PhoR sensor domain will facilitate the structure based drug discovery of novel anti- tubercular. In this study, we successfully predicted and isolated the gene encoding PhoR sensor domain from Mycobacterium tuberculosis H37Rv, cloned it in pGEM-T vector and subcloned it in pRSET emGFP expression vector. PhoR sensor domain was successfully cloned and would be used for further expression, purification and crystallization studies.

Choroidal Tuberculoma in an Immunocompetent Young Patient

TUBERCULOSIS （TB） remains one of the leading causes of preventable morbidity and mortality from infectious disease worldwide.1 It is a chronic progressive granulomatous infection caused by Mycobacterium tuberculosis （M. tuberculosis）.

Sequence analysis on drug-resistant rpoB gene of Mycobacterium tuberculosis L-form of isolated from pneumoconiosis workers

To study the characteristics of drug-resistant genetic mutation of rpoB on coal workers＇ pneumoconiosis complicated with L-form of Mycobacterium tuberculosis. Methods： A total of 42 clinical isolated strains of Mycobacterium tuberculosis L-forms were collected, including 31 drug-resistant strains. Their genomes DNA were extracted, the target genes were amplified by PCR, and the hot regions in the rpoB gene were analyzed by automated DNA sequenator. Results： No mutation of rpoB gene was identified in 11 rifampicin-sensitive strains while conformation changes were found in 31 rifampicin-resistant strains. The mutation rate was 93.55% （29/31） in resistant strains, mainly concentrated in codon 531 （51.6%, 16/31） and 526 （32.26%, 10/31）. Base substitutions happened, including 27 unit point mutation and 2 two point mutation. The mutation of codon 516 that new found wasn＇t reported by internal and overseas scholars. Conclusion： The substitution of highly conserved amino acids encoded by rpoB gene results in the molecular mechanism responsible for rifampicin resistance in Mycobacterium tuberculosis L-forms. It also proves that rpoB gene is diversiform.

Characterization of the Mycobacterium Tuberculosis Protein Rv2302

The Mycobacterium tuberculosis protein Rv2302 has been characterized using nuclear magnetic resonance （NMR） and circular dichroism （CD） spectroscopy. While the biochemical function of Rv2302 is still unknown, recent microarray analyses show that Rv2302 is upregulated in response to starvation and overexpression of heat shock proteins and, consequently, may play a role in the biochemical processes associated with these events. Rv2302 is a monomer in solution as shown by size exclusion chromatography and NMR spectroscopy. CD spectroscopy suggests that Rv2302 partially unfolds upon heating and that this unfolding is reversible. Using NMR-based methods, the solution structure of Rv2302 was determined. The protein contains a five-strand, antiparalle β-sheet core with one C-terminal α-helix （A61 to A75） nestled against its side. Hydrophobic interactions between residues in the α-helix and β-strands 3 and 4 hold the α-helix near the β-sheet core. The electrostatic potential on the solvent-accessible surface is primarily negative with the exception of a positive arginine pocket composed of residues R18, R70, and R74. Steady-state {^1H}-^15N heteronuclear nuclear Overhauser effects indicate that the protein＇s core is rigid on the picosecond timescale. The absence of amide cross-peaks for residues G 13 to H 19 in the ^1H-^15N heteronuclear single quantum correlation spectrum suggests that this region, a loop between β-strands 1 and 2, undergoes motion on the millisecond to microsecond timescale. Dali searches using the structure closest to the average structure do not identify any high similarities to any other known protein structure, suggesting that the structure of Rv2302 may represent a novel protein fold.

Nontuberculous Mycobacteria Infections in Katavi Rukwa Ecosystems

A study on nontuberculous mycobacteria （NTM） was carried out in wildlife-livestock interface of Katavi Rukwa ecosystem （KRE）. 328 livestock tissues and 178 wild animals were cultured, wild animals were sampled opportunistically during professional hunting and game cropping operations in the KRE protected areas. The objective of the study was to generate data on epidemiology of NTM in the wildlife-livestock interface of the KRE. Methods used to identify the NTM were： culture and isolation, polymerase chain reaction, protein heat shock 65 kilodalton （hsp65） and sequencing. Mycobacteria were detected on 25.9% and 11.9% of livestock and wildlife tissue cultures, respectively. The most NTM isolated were M. kansasii （30%）, M. gastri （30%）, M. fortuitum （1%）, M. intracellulare （4%）, M. indicuspranii （4%）, M. nonchromogenicum （6%） and M. lentiflavum （6%）. Other NTM in smaller percentages were M. hibernae, M. engbaekii, M. septicum, M. arupense and 34.. godii. Due to rise of NTM infection in both human and animals, it is recommended that awareness and laboratory facilities be improved to curb the underreporting especially in TB-endemic countries. For species specific identification, a network of national and regional laboratories is promoted.

Anti-mycobacterium and Anti-cancer Activities of Combretin, an Isolated Steroidal Alkaloid from the Seeds of Combretum quadrangulare Kurz.

Combretin is the steroidal alkaloid isolated from the seeds of Combretum quadrangulare Kurz. by macerated powder of the seeds with 95% ethanol. Purified further by avicel column chromatography and preparative thin layer chromatography. Combretin was investigated for anti-mycobacterium and anti-cancer activities. Combretin was inactive against Mycobacterium tuberculosis but showed anti-cancer activities against human hepatocarcinoma （Hep G2） ATCC HB-8065 and human caucasian colon adenocarcinoma （Caco2） ATCC HTB-39 at concentration greater than 300 mcg/ml in DMSO （Dimethyl sulfoxide）.

Fast species identification of mycobacterium by rpoB gene chip technology

Based on rpoB gene micro array as target gene, we are going to use gene chip technology to test 24 mycobacterium standard specimens, 8 non-mycobacterium specimens and 86 mycobacterium clinical isolated specimens. As a result, after mycobacterium and non-mycobacterium standard specimens were duplicated by PCR, mycobacterium standard specimens reproduced 360bp DNA fragments; on the other hand, non-mycobacterium specimens did not reproduce any fragments except for hemolytic streptococcus and corynebacterium pseudodiphtheriticum which had the same results as mycobacterium standard specimens. Sensitive test is able to detect lpg tuberculosis mycobacterium DNA. The probe test showed that, among 21 oligonucleotide probes, probe-M. fortuitum and M. marinum were cross-hybrid; the other probes were specific. We used the new method to identify 126 mycobacterium clinical isolated specimens. The test results of this new method matched with conventional method. In conclusion, compared to the traditional method, the use of rpob gene chip technology to identify mycobacterium species will be faster, more accurate and higher value in application.

CUTANEOUS MYCOBACTERIUM MARINUM INFECTION DIAGNOSED BY PCR-RFLP ANALYSIS

Objective To identify Mycobacterium marinum （M. marinum ） inducing misdiagnosis and treatment failure. Methods The lesional specimen of patient with cutaneous M. marinum were cultivated on L6wenstein-Jensen medium. The isolate was identified by biochemical tests and polymerase chain reaction （PCR）-restriction fragment length polymorphism （RFLP） analysis of the hsp65 gene. Results Smooth and non- pigmented colonies were noted after incubation at 32 ℃ for 2 weeks. The isolate was acid-fast bacilli and confirmed as M. marinum by biochemical tests and PCR-RFLP. Conclusion For a correct diagnosis of cutaneous M. marinum infection, it is crucial for clinicians to have a high index of suspicion, obtain the history of exposure and trauma and understand growth characteristics of the organism. Compared with conventional biochemical techniques, PCR-RFLP analysis is a more rapid, accurate and reliable method for mycobacterial identification to species level.

Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors

With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrinsic β-lactam resistance of M. tuberculosis is primarily due to the production of an Ambler class-A β-lactamase BlaC, which limits the application of β-lactam antibiotics in the treatment of tuberculosis. Therefore, the inhibitors of BlaC could be novel anti-tuberculosis drug synergistic agents to recover the sensibility of M. Tuberculosis to the β-lactam antibiotics. In the present study, BlaC of M. tuberculosis was expressed and purified to establish a screening model of the BlaC inhibitors. The screening conditions were determined, and the screening model was evaluated to fit for the high throughput screening. A total of 22 BlaC inhibitors were screened out from 26 400 compound samples with a positive rate of 0.083%. Taken together, our findings lay the foundation for the discovery of novel anti-tuberculosis drug synergistic agents in clinic.

Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis

This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF） to treat a mouse model of tuberculo- sis （TB） infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 （P〈0.01） and 0.58 （P〈0.05） lg colony-forming units （CFU）, respectively, and in the spleens by 1.42 （P〈0.01） and 1.22 （P〈0.01） lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens （1.02 and 1.34 lg CFU） compared with antibacterial therapy alone （P〈0.01）. This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis （MDR-TB）.

Genes and regulatory networks involved in persistence of Mycobacterium tuberculosis

The causative agent of tuberculosis,Mycobacterium tuberculosis,is one of the most successful of human pathogens.It can evade the host immune response and establish a persistent infection or enter a dormant state within the host which can be reactivated if the host becomes immuno-compromised.Both of these features are major obstacles to tuberculosis eradication.Dormancy and reactivation of M.tuberculosis are tightly coordinated dynamic processes involving numerous genes and their products.Molecular mechanisms underlying M.tuberculosis persistence may provide an opportunity for the discovery of effective drug targets for tuberculosis control.Here,we review the genes required for M.tuberculosis persistence and propose a regulatory network for the action of these genes using text mining.This should provide fresh insights into the persistence mechanisms of M.tuberculosis and suggest candidates for new drug targets and immune intervention.