Mechanism of Drug Resistance in Mycobacterium tuberculosis

Pym, Alex; Cole, Stewart T.

doi:10.1201/9781420008753.ch13

Cited by 4 publications

(8 citation statements)

References 170 publications

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“…Sequencing revealed two combined mutations of the rpoB gene region in some cases, but the combination did not change the resistance level [48]. Rifampicin resistance does not affect the viability and other prop erties of MT, although a certain decrease in virulence and a lower sensitivity to particular drugs was noted in several studies (for a review, see [10,46]). …”

Section: Rifampicin Resistancementioning

confidence: 96%

“…As for the third line drugs, the available data are still scarce. There are many original articles and several reviews in the field [5,10,44]. In addition, a summary of a TB drug resistance mutation database [45] was published recently; the database includes information on 946 resistance mutations described by September 2008; in particular, their chromosomal localization is indicated ( Table 2).…”

Section: Genetic and Molecular Mechanisms Of Mt Resistance To Antibiomentioning

confidence: 99%

“…The strains, which were most commonly resistant to isoniazid and rifampicin, were termed strains with multidrug resis tance (MDR). Since first line drugs proved ineffective in such cases, second line drugs were used and often led to additional resistance (to three to five drugs empirically, while an isolate has to be resistant to a minimum of two drugs to be qualified as MDR) (for a review, see [10,11]). …”

Section: Origin and Spreading Of Mycobacterium Tuberculosis Strains Wmentioning

confidence: 99%

“…Sensitive strains grow in the presence of 0.02-0.1 μg/ml isoniazid (on a solid medium); the range of the MIC and upper resistance levels in differ ent mutants are extremely great, from 0.2 to 50 μg/ml or even higher. Numerous studies characterized the resistance mutants (for a review, see [10,44,46]). …”

Section: Isoniazid Resistancementioning

confidence: 99%

“…Its biotarget is arabinosyltrans ferase, which is involved in biosynthesis of arabinoga lactan, an important component of the MT cell wall. Arabinosyltransferase is encoded by the emb gene, which belongs to the embCAB operon [55] (for a review, see [10,44]). Ethambutol resistance mutations arise at a frequency of 10 -5 in vitro.…”

Section: Ethambutol Resistancementioning

confidence: 99%

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Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

2012

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The review summarizes the data on the Mycobacterium tuberculosis mutations that lead to multi drug resistance (MDR) to various antibiotics. MDR strains arose over the past 30 years as a variety of antitu berculosis drugs were introduced in medicine, and they largely discount the results of chemotherapy for tuberculosis. The most dangerous of them are strains with extensive drug resistance (XDR), which are resis tant to four or five different drugs on average. The molecular mechanisms that make a strain resistant are con sidered. XDR and MDR strains result from successive and usually independent resistance mutations, which arise in various regions of the mycobacterial genome. In addition, the formation of resistant strains is affected by the phenomenon of tolerance and mycobacterial latency in infected tissues.

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Section: Rifampicin Resistancementioning

confidence: 96%

Section: Genetic and Molecular Mechanisms Of Mt Resistance To Antibiomentioning

confidence: 99%

Section: Origin and Spreading Of Mycobacterium Tuberculosis Strains Wmentioning

confidence: 99%

Section: Isoniazid Resistancementioning

confidence: 99%

Section: Ethambutol Resistancementioning

confidence: 99%

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Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

2012

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A review on anti‐tuberculosis peptides: Impact of peptide structure on anti‐tuberculosis activity

Yathursan

Wiles

Read

et al. 2019

Journal of Peptide Science

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Antibiotic resistance is a major public health problem globally. Particularly concerning amongst drug‐resistant human pathogens is Mycobacterium tuberculosis that causes the deadly infectious tuberculosis (TB) disease. Significant issues associated with current treatment options for drug‐resistant TB and the high rate of mortality from the disease makes the development of novel treatment options against this pathogen an urgent need. Antimicrobial peptides are part of innate immunity in all forms of life and could provide a potential solution against drug‐resistant TB. This review is a critical analysis of antimicrobial peptides that are reported to be active against the M tuberculosis complex exclusively. However, activity on non‐TB strains such as Mycobacterium avium and Mycobacterium intracellulare, whenever available, have been included at appropriate sections for these anti‐TB peptides. Natural and synthetic antimicrobial peptides of diverse sequences, along with their chemical structures, are presented, discussed, and correlated to their observed antimycobacterial activities. Critical analyses of the structure allied to the anti‐mycobacterial activity have allowed us to draw important conclusions and ideas for research and development on these promising molecules to realise their full potential. Even though the review is focussed on peptides, we have briefly summarised the structures and potency of the various small molecule drugs that are available and under development, for TB treatment.

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Treatment Outcomes Among Pediatric Patients With Highly Drug-Resistant Tuberculosis: The Role of New and Repurposed Second-Line Tuberculosis Drugs

Madzgharashvili

Salindri

Magee

et al. 2020

Journal of the Pediatric Infectious Diseases Society

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Background Among pediatric patients with multidrug-resistant tuberculosis (MDR-TB), limited data exist regarding treatment outcomes in the context of the new and repurposed second-line TB drugs (SLDs). We aimed to describe the treatment outcomes among pediatric MDR-TB patients receiving new and repurposed SLDs including the proportion who achieved favorable outcomes. Methods We conducted a retrospective cohort study among pediatric patients (age ≤18 years) treated for MDR-TB in the country of Georgia from 2009 to 2016. A “new and repurposed” SLD regimen was defined as a regimen that included linezolid, bedaquiline, and/or delamanid. Favorable treatment outcome was defined by treatment completion or documented microbial “cure” status at the end of treatment. We assessed the association between the use of the new and repurposed SLDs with MDR-TB treatment outcomes using bivariate analyses and log-binomial regression. Results There were 124 pediatric MDR-TB patients (median age: 13.7; interquartile range: 4.6-16.0) initiating treatment; 119 (96.0%) had a treatment outcome recorded and were included in our analyses. Eighteen (15.1%) patients received new and repurposed SLDs from 2015 or later. After adjusting for potential confounders, the proportion achieving favorable MDR-TB treatment outcomes was higher among patients treated with SLD regimens that included new and/or repurposed drugs when compared with those treated without (adjusted risk ratio: 1.17; 95% confidence interval: 0.51-2.72). Conclusions We observed a high proportion of favorable treatment outcomes among pediatric patients with MDR-TB receiving the new and repurposed SLDs. Further studies to evaluate the efficacy and children’s tolerability of the new and repurposed SLDs are still warranted.

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Mechanism of Drug Resistance in Mycobacterium tuberculosis

Cited by 4 publications

References 170 publications

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

A review on anti‐tuberculosis peptides: Impact of peptide structure on anti‐tuberculosis activity

Treatment Outcomes Among Pediatric Patients With Highly Drug-Resistant Tuberculosis: The Role of New and Repurposed Second-Line Tuberculosis Drugs

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