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Mechanisms of drug resistance in Mycobacterium tuberculosis PDF

Drug-resistant tuberculosis (DR-TB), including multi-and extensively drug-resistant TB, is posing a significant challenge to effective treatment and TB control world-wide. New progress has been made in our understanding of the mechanisms of resistance to anti-tuberculosis drugs. This review provides an update on the majo Drug Resistance Mechanisms in Mycobacterium tuberculosis Juan Carlos Palomino * and Anandi Martin Laboratory of Microbiology, Department of Biochem istry and Microbiology, Ghent University gens, such as Mycobacterium tuberculosis, nothing can prevent the emergence of drug-resistant strains. Several mechanisms facilitate drug resistance in M. tuberculosis including compensatory evolution, epistasis, clonal interference, cell wall integrity, efflux pumps, and target mimicry

Tuberculosis is a worldwide health problem posing increasing threat with the spread of HIV infection and drug resistant Mycobacterium tuberculosis strains. Consequently, control of this disease has become a significant challenge despite the availability of chemotherapy and BCG vaccine. Drug resistance for all first-line anti-tuberculosis agents and some second-line agents has been observed Drug-resistant tuberculosis, Edited by C-Y. Chiang NUMBER 1 IN THE SERIES [A version in French of this article is available from the Editorial Offi ce in Paris and from the Union website www.theunion.org] Mechanisms of drug resistance in Mycobacterium tuberculosis Y. Zhang,* W. W. Yew†Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease.In recent years, even more serious forms of drug resistance have been reported In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed. Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to ac

Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular. Drug-resistant tuberculosis (DR-TB), including multi- and extensively drug-resistant TB, is posing a significant challenge to effective treatment and TB control worldwide. New progress has been made in our understanding of the mechanisms of resistance to anti-tuberculosis drugs. This review provides an update on the major advances in drug. Request PDF | Mechanisms of drug resistance in Mycobacterium tuberculosis | Tuberculosis is a worldwide health problem posing increasing threat with the spread of HIV infection and drug resistant. Cole ST (1994) Drug resistance mechanisms employed by Mycobacterium tuberculosis. Trends Microbiol 2: 412-415 Google Scholar. Cole ST, Smith DR (1994) Toward mapping and sequencing the genome of Mycobacterium tuberculosis. In: Bloom BR (ed) Tuberculosis: pathogenesis, protection, and control Molecular mechanisms of drug resistance have been elucidated for the major first- and second-line drugs rifampicin, isoniazid, pyrazinamide, ethambutol, the aminoglycosides and the fluoroquinolones. The relationship between drug resistance in M. tuberculosis strains and their virulence/transmissibility needs to be further investigated

(PDF) Drug Resistance Mechanisms in Mycobacterium tuberculosi

[PDF] Mechanisms of drug resistance in Mycobacterium

  1. Download Free PDF. Download Free PDF. Open Access Targeting Drug Resistance Mechanisms in Mycobacterium tuberculosis Thanh Pham, Tung Nguyen and Liem Nguyen* Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA An Ancient Disease Returns One of.
  2. molecular mechanisms of drug resistance in M. tuberculosis. The outbreak of MDR-TB in New York City in the late 1980s and early 1990's has drawn much media attention. The first molecular study of drug resistance mechanisms in M. tuberculosis was that by Zhang and colleagues in 1992 on the mechanism of isoniazid resistance in M. tuberculosis (2)
  3. gly high, with ∼10.4 million incident cases and ∼1.5 million deaths reported by the WHO in 2015. 1, Mycobacterium tuberculosis (MTB) strains displaying in vitro resistance to isoniazid and rifampicin accounted for ∼480 000 incident cases and 250 000 deaths in 2015. 1.
  4. Drug-resistant tuberculosis (DR-TB), including multiand extensively drug-resistant TB, is posing a significant challenge to effective treatment and TB control worldwide. New progress has been made in our understanding of the mechanisms of resistance to anti-tuberculosis drugs. This review provides an update on the major advances in drug.
  5. (PDF pdf icon - 37k) Multidrug-Resistant Tuberculosis (MDR TB) What is tuberculosis (TB)? Tuberculosis (TB) is a disease caused by bacteria that are spread from person to person through the air. TB usually affects the lungs, but it can also affect other parts of the body, such as the brain, the kidneys, or the spine
  6. Understanding resistance mechanisms is vital for the safe and effective treatment of patients, as well as for long-term antibiotic stewardship. The early and comprehensive elucidation of resistance mechanisms to drugs for tuberculosis during drug development is in the common interest of patients, clinicians, academics, and pharmaceutical companies
  7. For some drugs, the mechanisms of action have not been fully identified. About the Illustrations. The photo of Mycobacterium tuberculosis is from the Centers for Disease Control and Prevention, CDC/Dr. Ray Butler, Janice Carr. This illustration is in the public domain

Molecular mechanisms of drug resistance in Mycobacterium

In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed. Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to act on the same targets in M. tuberculosis as they do in E. coli In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed. Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to act on the same targets in M. tuberculosis as they do in E. coli. Resistance to these agents. The primary mechanism of acquisition of drug resistance in Mycobacterium tuberculosis (Mtb) is spontaneous mutations in specific drug target genes acquired during DNA replication or mismatch repair failure . However alternate mechanisms also play a role in acquisition of drug resistance [6, 13]. Several intrinsic mechanisms including low cell.

Antibiotics | Special Issue : Mechanisms of Antibiotic

Mycobacterium tuberculosis (MTB) is commonly used as a model to study pathogenicity and multiple drug resistance in bacteria. These MTB characteristics are highly dependent on the evolution and. Multidrug-resistant TB (MDR-TB), caused by a strain of Mycobacterium tuberculosis resistant to at least rifampicin and isoniazid, and extensively drug-resistant TB (XDR-TB), caused by strains of M. tuberculosis that, in addition to being MDR, are also resistant to any fluoroquinolone and to at least one of the three injectable drugs kanamycin.

Mechanisms of drug resistance in Mycobacterium

Mycobacterium tuberculosis —the bacterium responsible for causing tuberculosis—is known for its ability to live inside macrophages, which are immune system cells that kill harmful bacteria. Over the last few decades, the continuous spread of M. tuberculosis drug resistance to extensively used therapeutics has become a significant clinical. drug-resistant M. tuberculosis,haveprovidedamore complete account of the genomic features that cause treat-ment resistance, enabling the identification of novel resist-ance mechanisms for existing drugs, and the determination of the mechanisms of action of newly discovered drugs. Identifying resistance determinants in laboratory-derived mutant South Africa, with a Tuberculosis (TB) incidence of 948/100 000 per annum and 15 914 Multi Drug Resistant (MDR) cases reported in 2007, was declared by the WHO as one of the countries with the highest burden of TB (16). MDR-TB is defined as Mycobacterium tuberculosis (M. tuberculosis) strain the spread of extensively drug-resistant tuberculosis (XDR-TB).2 Since the inclu-sion of MDR-TB management in the new and comprehensive Stop TB Strategy (17, 18), a new and fundamental role of the Global Project has been to assist 1 MDR-TB: Mycobacterium tuberculosis with resistance to isoniazid and rifampicin

Introduction This fifth edition of the Guidelines for surveillance of drug resistance in tuberculosis is an updated version of earlier editions published in 1994 (1), 1997 (2), 2003 (3) and 2009 (4). The document takes into account recent advancements in laborator Tuberculosis (TB) is a formidable infectious disease that remains a major cause of death worldwide today. Escalating application of genomic techniques has expedited the identification of increasing number of mutations associated with drug resistance in Mycobacterium tuberculosis. Unfortunately the prevalence of bacillary resistance becomes alarming in many parts of the world, with the daunting.

Mechanisms of Drug Resistance in Mycobacterium tuberculosi

Majority of the problems in treating Tuberculosis (TB) is the appearance of drug resistant TB strains, including strains with multiple drug resistance (MDR) and more recently, strains with extensive drug resistance (XDR). From the various MDR mechanisms, main focus is on efflux pumps as they contribute to MDR of Mycobacterium tuberculosis (MTB. Resistance to anti-tuberculous (anti-TB) drugs is attributed mainly to specific mutations in target genes; however, a proportion of drug-resistant MTB isolates do not have mutations in these genes, which suggests the involvement of other mechanisms, such as the low permeability of the mycobacterial cell wall, enzymatic modification and/or.

Identification of New Drug Targets and Resistance

Abstract. Tuberculosis (TB) is a leading chronic bacterial infection caused by Mycobacterium tuberculosis (M. tuberculosis) and an increasing public health threat.The current therapeutic management of M. tuberculosis is insufficient due to the prolonged course of treatment, side effects of drugs, and unorganized therapy, and these aspects can lead to therapeutic failure and development of drug. Successful treatment of tuberculosis (TB) can be hampered by Mycobacterium tuberculosis populations that are temporarily able to survive antibiotic pressure in the absence of drug resistance-conferring mutations, a phenomenon termed drug tolerance. We summarize findings on M. tuberculosis tolerance published in the past 20 years. Key M. tuberculosis responses to drug pressure are reduced.

a word about treating drug-resistant tuberculosis Hard data are often lacking to assist clinicians in the management of drug-resistant TB. Many of the drugs used to treat drug-resistant TB are not Food and Drug Administration (FDA)-licensed for these indications. Ex-amples include amikacin, all of the fluoroquinolones, and rifabutin multidrug drug-resistant tuberculosis, Mycobacterium tuberculosis, tuberculosis. Correspondence Tulika Prasad, Room #14, AIRF, Jawaharlal their mode of action and drug resistance mechanisms in Mtb. The knowledge is likely to facilitate better under-standing of drug resistance for effective TB therapy an This chapter reviews the discovery of drug resistance determinants in Mycobacterium tuberculosis and also provides an overview of all the mechanisms currently known for all the tuberculosis (TB) drugs. It discusses the mechanisms of drug resistance and drug action in M. tuberculosis and it is useful to start with some important general considerations The treatment of tuberculosis is extremely long. One of the reasons why Mycobacterium tuberculosis elimination from the organism takes so long is that in particular environmental conditions it can become tolerant to drugs and/or develop persisters able to survive killing even from very high drug concentrations. Tolerance develops in response to a harsh environment exposure encountered by. Tuberculosis (TB), caused by Mycobacterium tuber- culosis, is a major global public health issue.South - east Asia contributes notably (44%) to global TB cases. Thailand is in the top 30 countries for drug-resistant (DR) TB incidence (1).DR TB, including rifampin

β-Lactams are one of the most useful classes of antibiotics against many common bacterial pathogens. One exception is Mycobacterium tuberculosis. However, with increasing incidence of multidrug. Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is the deadliest infectious disease and the associated global threat has worsened with the emergence of drug resistance, in particular multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Although the World Health Organization (WHO) End-TB Strategy advocates for universal access to antimicrobial susceptibility.

(PDF) Targeting Drug Resistance Mechanisms in

  1. Identification of New Drug Targets and Resistance Mechanisms in Mycobacterium tuberculosis . View/ Open. 3781026.pdf (852.3Kb) K. C. Murphy, et al. 2013. Identification of New Drug Targets and Resistance Mechanisms in Mycobacterium tuberculosis. targets is vital for the advancement of drug discovery against Mycobacterium.
  2. g.
  3. Objective: This study analyzed drug resistance and mutations profiles in Mycobacterium tuber-culosis isolates in a surveillance site in Huairou District, Beijing, China. Methods: The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs
  4. Isoniazid (INH) is one of the most active compounds used to treat tuberculosis (TB) worldwide. In addition, INH has been used as a prophylactic drug for individuals with latent Mycobacterium tuberculosis (MTB) infection to prevent reactivation of disease. Importantly, the definition of multidrug resistance (MDR) in TB is based on the resistance of MTB strains to INH and rifampicin (RIF)

Evolution of drug resistance in Mycobacterium tuberculosis

  1. Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is.
  2. BackgroundIn South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic.MethodsIn an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium.
  3. In order to shorten the course of treatment and its effectiveness, it is essential to gain an in-depth insight into the drug resistance mechanisms of Mycobacterium tuberculosis (M. tuberculosis). In this study, we evaluated the contribution of 26 drug efflux pumps plus target gene mutations to the drug resistance levels in multi-drug resistant (MDR)/pre-extensively drug-resistant (pre-XDR.
  4. Abstract. Tuberculosis (TB) remains one of the leading public health problems worldwide. Declared as a global emergency in 1993 by the WHO, its control is hampered by the emergence of multidrug resistance (MDR), defined as resistance to at least rifampicin and isoniazid, two key drugs in the treatment of the disease

Overview of drug resistant Mycobacterium tuberculosis strain types in Africa Molecular epidemiological data. The molecular mechanisms of drug resistance as well as the evolution of drug resistant strains in Africa have been studied using a variety of genotyping tools [10,11,12,13].This has provided some insight into the transmission dynamics of drug resistant TB Background: The burden of drug resistant tuberculosis in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains. MDR-TB is defined as resistance to isoniazid and rifampicin, while XDR-TB is defined as MDR-TB with added resistance to any of th Current knowledge on the mechanisms of Mtb drug resistance is presented in the subsequent section (Palomino and Martin 2014; Dookie et al. 2018). Drug resistance mechanisms in Mycobacterium. Drug resistance is a major impediment to TB treatment and poses a challenge to global public health and therapeutics

Fact Sheets Drug-Resistant TB Multidrug-Resistant

Drug-resistant Mycobacterium tuberculosis complex (MTBC) strains are estimated to account for one third of all deaths due to antimicrobial resistance globally [1]. Owing to the inherently slow growth rate of MTBC, the only realistic way to diagnose the majority of drug-resistant cases is to use rapid genotypic drug-susceptibilit The treatment ofMycobacterium tuberculosis with drugs such as isoniazid often results in drug resistance, but the mechanisms leading to the resistance are not fully known. In this study, an M. Multi Drug Resistant Tuberculosis MDR-TB Dr.T.V.Rao MD 13. 14. Definition MDR-TB caused by strains of Mycobacterium Tuberculosis resistant both Rifampicin and Isoniazid with or without resistance to other drugs. Single Isoniazid or Rifampicin resistance is not MDR - TB MDR TB is a laboratory diagnosis Dr.T.V.Rao MD 14. 15 Mycobacterium tuberculosis ( Mtb ) causes the disease tuberculosis (TB), which kills more people than any other infection. The emergence of drug-resistant Mtb strains has exacerbated this already alarming epidemic. We have identified a small molecule, C10, that potentiates the activity of the frontline antibiotic isoniazid (INH) and prevents the selection for INH-resistant mutants Most β-lactam antibiotics are ineffective against Mycobacterium tuberculosis due to the microbe's innate resistance. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has prompted interest to repurpose this class of drugs. To identify the genetic determinants of innate β-lactam resistance, we carried out a synthetic lethality screen on a transposon.

Drug-resistance mechanisms and tuberculosis drugs - The Lance

Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis Mashael Al-Saeedi, Sahal Al-Hajoj Department of Infection and Immunity, Mycobacteriology Research Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Abstract: Despite the efficacy of antibiotics to protect humankind against many deadly pathogens, such as Mycobacterium. Acquired resistance of Mycobacterium tuberculosis to bedaquiline. PLoS One 9:e102135. ^ Zhang S, Chen J, Cui P, Shi W, Zhang W, Zhang Y. 2015. Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis. J Antimicrob Chemother 70:2507-2510. ^ Shepard CC, Chang YT. 1962. Effect of several anti-leprosy. The current TB regimen is long and complex, failing of which leads to relapse and/or the emergence of drug resistance. There is a critical need to understand the mechanisms of resistance development. With increasing drug pressure, Mycobacterium tuberculosis (Mtb) activates various pathways t Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs), isoniazid and rifampin.Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB ()..

Tuberculosis Drugs and Mechanisms of Action NIH

Since 2002 there has been a gradual, 1.3% per year, decrease in the incidence of tuberculosis (TB) worldwide. Though this is encouraging, this level of reduction will not meet the goal of the World Health Organization (WHO) to eliminate TB by 2050. In addition, the problem is only being compounded by the growing incidence of drug-resistant tuberculosis (Dye et al., 2013) The continued and accelerated emergence of anti-microbial resistance is a global threat and antimicrobial-resistant infections caused by Mycobacterium tuberculosis (Mtb) are particularly concerning. In 2018, approximately 484,000 people developed multidrug-resistant tuberculosis and an estimated 214,000 people died from rifampicin-resistant or multidrug-resistant tuberculosis (Geneva: World. Poudel A, Nakajima C, Fukushima Y, et al. Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolated in Nepal. Antimicrob Agents Chemother 2012; 56:2831. Taype CA, Agapito JC, Accinelli RA, et al. Genetic diversity, population structure and drug resistance of Mycobacterium tuberculosis in Peru

Molecular Mechanisms of Drug Resistance in Mycobacterium

Video: Deregulation of Genes Associated with Alternate Drug

(PDF) Drug resistance in Mycobacterium tuberculosis

mechanisms and models of care. However, psychosocial support to ensure comprehensive management of the patients, strategies for infection prevention and control, and occupational health services for health care workers (HCWs) are covered. Legal issues around the management of drug-resistant tuberculosis (DR-TB) are complex and hav LPAs aim to improve the sensitivity of (Mycobacterium tuberculosis complex) MTBC detection and to simultaneously detect resistance to rifampicin (Rif) and isoniazid (H). n 2I 015, FNI D (the Foundatoi n for Innovatvi e New Diagnostci s) evaul ated the Npi ro and the GenoType MTBDR plus V2 LPAs and compared them with the GenoType MTBDR plus V1 Drug resistance in pathogenic bacteria such as Mycobacterium tuberculosis can be predicted by an application of machine learning models to next-generation sequencing data. The received wisdom is that following standard protocols for training commonly used machine learning models should produce accurate drug resistance predictions

Microorganisms | Free Full-Text | Metabolite Profiling: A

Drug resistance of mycobacterium tuberculosis (MTB), especially multidrug resistant tuberculosis (MDR-TB, defined as resistance to at least rifampin and isoniazid) has contributed to a significant health and economic burden on a global scale [1,2,3].Drug-resistant tuberculosis (DR-TB) can be transmitted (primary resistance, refers to the infection with drug-resistant MTB) or develop during the. •Increasing resistance to second-line drugs due to frequent changes in regimens (often due to toxicity), poor adherence, too few effective drugs available for regimen WHO; Guidelines for the programmatic management of drug-resistant tuberculosis: Emergency Update 2008 1 Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of multi-drug resistant tuberculosis in decades. In vitro resistance to BDQ was previously shown to be due to target-based mutations. Here we report that non-target based resistance to BDQ, and cross-resistance to clofazimine (CFZ), is due to mutations in Rv0678, a transcriptional repressor of the. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been. In order to combat the threat of drug resistant tuberculosis and to more effectively control the disease, an understanding of the mechanisms underlying drug resistance is necessary. This knowledge could be used for the development of molecular tests for rapid detection of drug resistant bacilli and future anti-tuberculosis drugs

Genome sequence analysis of multidrug-resistant

  1. encoded in the genome of M. tuberculosis, of which 19 were correlated with drug resistance. Pumps had between 10 and 16 transmembrane domains and could be categorised into nine families,includingdrug-protonantiporterfamilies1and2(DHA1andDHA2),eachstronglyasso-ciated with drug resistance [36]
  2. The bacteria that cause tuberculosis (TB) can develop resistance to the antimicrobial drugs used to cure the disease. Multidrug-resistant TB (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs. The 2 reasons why multidrug resistance continues to emerge and spread are mismanagement of TB.
  3. In vitro, Mycobacterium tuberculosis (Mtb) acquired resistance to these compounds through three discrete mechanisms: (1) a decrease in drug metabolism via loss-of-function mutations in the amidase that hydrolyses these carboxamides, (2) an increased biosynthetic rate of tryptophan precursors via loss of allosteric feedback inhibition of.
  4. Mechanisms of drug resistance in Mycobacterium tuberculosis Y.Zhang,~* W.W.Yew~+ * Department of Molecular Microbiology and Immunology,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,Maryland,USA;+ Tuberculosis and Chest Unit,Grantham Hospital,Hong Kong,Chin
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Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line drugs.Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is. Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis [Corrigendum] On page 339, an Acknowledgment section should have been included as follows: This study has been funded by King AbdulazizCity for Science and Technology, Riyadh, Saudi Arabia, under the National Science, Technology and Innovation Plan (NSTIP) (grant #11-BIO-1436-20) Lack of evidence in drug-resistant tuberculosis clinical and operational management 4 Objectives of the Guidelines 4 References 5 2 Historical background and global epidemiology of Mycobacterium tuberculosis resistance 7 Historical background of anti-tuberculosis drug resistance 7 Surveillance of anti-tuberculosis drug resistance 2 2 Abstract Background: Drug resistance tuberculosis (DR-TB) continues to be a major public health threat globally. Due to the development of many rapid molecular diagnostic tools to detect gene mutations in M.tuberculosis (Mtb), specific genes conferring resistance to different anti-TB drugs have been identified. The aim of this meta-analysis was to assess the prevalence of the gene.