Mechanism of Drug Resistance in Mycobacterium Tuberculosis

Abraham, Ayanwale O; Nasiru, Adabara U; AbdulAzeez, Adeniyi K; Seun, Oyewole O; Ogonna, David W

doi:10.34297/ajbsr.2020.07.001181

Cited by 11 publications

(7 citation statements)

References 55 publications

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“…2. Механизм действия R заключается в связывании с ß-субъединицей РНК-полимеразы, участвующей в удлинении матричной РНК, а мутации в rpoB приводят к развитию резистентности МБТ к этому препарату [4].…”

Section: материалы и методыunclassified

Prevalence and Patterns of Gene Mutations Associated with <i>M. tuberculosis</i> Resistance to Isoniazid and Rifampicin in Patients with Different Clinical Manifestations of Tuberculosis

Салина

Morozova

2023

Tuberk. bolezni lëgk.

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The objective: to study prevalence and patterns of mutations in the katG, inhA, ahpC, rpoB genes associated with Mycobacterium tuberculosis (MTB) resistance to isoniazid (H) and rifampicin (R) in patients with various clinical manifestations of pulmonary tuberculosis (TB).Subjects and Methods. 441 sputum samples collected in tuberculosis patients were tested using biological microchips. Tests were carried out in Group 1 - patients with confirmed bacterial excretion (n = 256) and in Group 2 (n = 185) - patients without bacterial excretion. The same patients were enrolled in Group 3 - patients with acute progressing tuberculosis (n = 52) and Group 4 (n = 99) - patients with localized tuberculosis.Results. In Group 1, DNA of Mycobacterium tuberculosis was found in 79.3% of patients, in Group 2 - in 57.8%. Among all samples, mutations in the genes encoding resistance to isoniazid were detected in 15.5%, resistance to rifampicin - in 58.1%. Resistance to isoniazid was more often caused by mutations in the katG gene (49%) versus the inhA (29%) and ahpC (4.2%) genes. We found 13 most common types of mutations in the rpoB gene associated with resistance to rifampicin. The dominant mutations in both groups were Seu531->Leu mutations - 19.7% in Group 1 and 24.3% in Group 2. In Group 1, mutations in the katG gene (53.7%) were observed more often than mutations in the inhA gene (27.7%). In Group 3, mutations in the katG gene were registered in 30.8%, in the inhA gene - in 25%. There were no statistically significant differences in patterns of mutations in the katG, inhA, ahpC, rpoB genes between Groups 1, 2 and 3, 4. Thus, patients without bacterial excretion and patients with localized tuberculosis are a hidden dangerous reservoir of tuberculous mycobacteria with multiple drug resistance to rifampicin and drug resistance to isoniazid.

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Section: материалы и методыunclassified

Prevalence and Patterns of Gene Mutations Associated with <i>M. tuberculosis</i> Resistance to Isoniazid and Rifampicin in Patients with Different Clinical Manifestations of Tuberculosis

Салина

Morozova

2023

Tuberk. bolezni lëgk.

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“…The currently recommended treatment for drug‐susceptible M. tuberculosis is a 6–9-month-long regimen with a combination of four first‐line drugs: isoniazid, rifampicin, ethambutol, and pyrazinamide (Honeyborne et al 2019 ). The epidemic occurred due to inadequate treatment regimens, which often lead to drug‐resistant strains that represent a major threat to global public health (Abraham et al 2020 ). In 2015, a 90% reduction in TB deaths and 80% in TB incidence was predicted by the WHO in its 2030 goals (WHO 2017 ).…”

Section: The Need For New Secondary Metabolitesmentioning

confidence: 99%

Impact of novel microbial secondary metabolites on the pharma industry

Ramírez-Rendon

Passari

Ruíz-Villafán

et al. 2022

Appl Microbiol Biotechnol

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Microorganisms are remarkable producers of a wide diversity of natural products that significantly improve human health and well-being. Currently, these natural products comprise half of all the pharmaceuticals on the market. After the discovery of penicillin by Alexander Fleming 85 years ago, the search for and study of antibiotics began to gain relevance as drugs. Since then, antibiotics have played a valuable role in treating infectious diseases and have saved many human lives. New molecules with anticancer, hypocholesterolemic, and immunosuppressive activity have now been introduced to treat other relevant diseases. Smaller biotechnology companies and academic laboratories generate novel antibiotics and other secondary metabolites that big pharmaceutical companies no longer develop. The purpose of this review is to illustrate some of the recent developments and to show the potential that some modern technologies like metagenomics and genome mining offer for the discovery and development of new molecules, with different functions like therapeutic alternatives needed to overcome current severe problems, such as the SARS-CoV-2 pandemic, antibiotic resistance, and other emerging diseases. Key points • Novel alternatives for the treatment of infections caused by bacteria, fungi, and viruses. • Second wave of efforts of microbial origin against SARS-CoV-2 and related variants.• Microbial drugs used in clinical practice as hypocholesterolemic agents, immunosuppressants, and anticancer therapy. Keywords Microbial natural products • Antibiotics • Hypocholesterolemics• Anticancer drugs • Immunosuppressants • Antibiotic resistance Abbreviations FDA Food and Drug Administration NA Not applicable cSSSI Complicated skin, and skin structure infections ABSSSIs Acute bacterial skin, and skin structure infections cUTI Complicated urinary tract infections cIAI Complicated intra-abdominal infections HABP/VABP Hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia CABP Community-acquired bacterial pneumonia. Estimate of U.S. Sales for 2018 was based on data previously reported Carr and Stringer 2019 * Sergio Sánchez

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“…For example, in studies conducted by Khalilzadeh et al and Song et al, clinical isolates of M. tuberculosis showed primary resistance towards rifampicin, isoniazid, streptomycin, and ethambutol [55] , [56] . Rifampicin and isoniazid resistance is associated with mutations in the rpoB gene of the RNA polymerase and katG , inhA , ahpC , kasA genes, respectively [48] , [57] .…”

Section: Multidrug Resistancementioning

confidence: 99%

Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics

Sharma

Barman

Joshi

et al. 2022

Colloids and Surfaces B: Biointerfaces

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The decreasing effectiveness of conventional drugs due to multidrug-resistance is a major challenge for the scientific community, necessitating development of novel antimicrobial agents. In the present era of coronavirus 2 (COVID-19) pandemic, patients are being widely exposed to antimicrobial drugs and hence the problem of multidrug-resistance shall be aggravated in the days to come. Consequently, revisiting the phenomena of multidrug resistance leading to formulation of effective antimicrobial agents is the need of the hour. As a result, this review sheds light on the looming crisis of multidrug resistance in wake of the COVID-19 pandemic. It highlights the problem, significance and approaches for tackling microbial resistance with special emphasis on anti-microbial peptides as next-generation therapeutics against multidrug resistance associated diseases. Antimicrobial peptides exhibit exceptional mechanism of action enabling rapid killing of microbes at low concentration, antibiofilm activity, immunomodulatory properties along with a low tendency for resistance development providing them an edge over conventional antibiotics. The review is unique as it discusses the mode of action, pharmacodynamic properties and application of antimicrobial peptides in areas ranging from therapeutics to agriculture.

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Mechanism of Drug Resistance in Mycobacterium Tuberculosis

Cited by 11 publications

References 55 publications

Prevalence and Patterns of Gene Mutations Associated with <i>M. tuberculosis</i> Resistance to Isoniazid and Rifampicin in Patients with Different Clinical Manifestations of Tuberculosis

Prevalence and Patterns of Gene Mutations Associated with <i>M. tuberculosis</i> Resistance to Isoniazid and Rifampicin in Patients with Different Clinical Manifestations of Tuberculosis

Impact of novel microbial secondary metabolites on the pharma industry

Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics

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