A comparison of Rv0559c and Rv0560c expression in drug-resistant Mycobacterium tuberculosis in response to first-line antituberculosis drugs

The significant increase in the detection of drug-resistant strains of Mycobacterium tuberculosis caused an urgent need for the discovery new antituberculosis drugs. Development of bioinformatics and computational sciences enabled the progress of new strategies leading to design, discovery and identification of a series of interesting drug candidates. In this short review, we would like to present recently discovered compounds targeting important mycobacterial proteins: DNA topoisomerases and the transcriptional repressor of EthA monooxygenase – EthR.

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Lipoprotein Processing Is Essential for Resistance of Mycobacterium tuberculosis to Malachite Green

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00647-09 ◽

2009 ◽

Vol 53 (9) ◽

pp. 3799-3802 ◽

Cited By ~ 17

Author(s):

Niaz Banaei ◽

Eleanor Z. Kincaid ◽

S.-Y. Grace Lin ◽

Edward Desmond ◽

William R. Jacobs ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Malachite Green ◽

Cell Envelope ◽

Sodium Dodecyl ◽

Signal Peptidase ◽

Wild Type ◽

First Line ◽

Green Is ◽

Antituberculosis Drugs ◽

Forming Efficiency

ABSTRACT Malachite green, a synthetic antimicrobial dye, has been used for over 50 years in mycobacterial culture medium to inhibit the growth of contaminants. The molecular basis of mycobacterial resistance to malachite green is unknown, although the presence of malachite green-reducing enzymes in the cell envelope has been suggested. The objective of this study was to investigate the role of lipoproteins in resistance of Mycobacterium tuberculosis to malachite green. The replication of an M. tuberculosis lipoprotein signal peptidase II (lspA) mutant (ΔlspA::lspA mut) on Middlebrook agar with and without 1 mg/liter malachite green was investigated. The lspA mutant was also compared with wild-type M. tuberculosis in the decolorization rate of malachite green and sensitivity to sodium dodecyl sulfate (SDS) detergent and first-line antituberculosis drugs. The lspA mutant has a 104-fold reduction in CFU-forming efficiency on Middlebrook agar with malachite green. Malachite green is decolorized faster in the presence of the lspA mutant than wild-type bacteria. The lspA mutant is hypersensitive to SDS detergent and shows increased sensitivity to first-line antituberculosis drugs. In summary, lipoprotein processing by LspA is essential for resistance of M. tuberculosis to malachite green. A cell wall permeability defect is likely responsible for the hypersensitivity of lspA mutant to malachite green.

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Peer Review #1 of "Rapid screening mutations of first-line-drug-resistant genes in Mycobacterium tuberculosis strains by allele-specific real-time quantitative PCR (v0.2)"

10.7287/peerj.6696v0.2/reviews/1 ◽

2019 ◽

Keyword(s):

Mycobacterium Tuberculosis ◽

Peer Review ◽

Quantitative Pcr ◽

Rapid Screening ◽

Drug Resistant ◽

First Line ◽

Real Time Quantitative Pcr ◽

Resistant Genes ◽

Allele Specific ◽

Line Drug

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Modelling the Transitional Dynamics of Mycobacterium Tuberculosis Strain

Journal of Medical and Biomedical Sciences ◽

10.4314/jmbs.v5i2.3 ◽

2016 ◽

Vol 5 (2) ◽

pp. 13-23

Author(s):

A. Alhassan ◽

K.S. Nokoe

Keyword(s):

Mycobacterium Tuberculosis ◽

Markov Chain Model ◽

Acquired Resistance ◽

World Health ◽

Chain Model ◽

Drug Resistant ◽

Transitional Dynamics ◽

Biomedical Sciences ◽

First Line ◽

Discrete State

The World Health Organization’s targets of eliminating Tuberculosis (TB) by 2050 is challenged by the emergence and spread of drug resistance TB. However, the traditional mechanism of resistance is that of acquired resistance, whereby the mycobacterium Tuberculosis (MTB) strain develops mutations under selective pressure of insufficient drug therapy. These mutations have the tendency of changing the drug target protein, restricting the bacteria to the anti-TB agent. We propose a discrete state markov chain model with three disease states: Drug Susceptible (DS), Multi Drug Resistant (MDR) and Extra Drug Resistant (XDR) to further study the transitional dynamics of the MTB strain. The study made use of a retrospective data on resistant pattern to first line and second line anti TB drugs. The structural properties of the model established life expectancies of DS and MDR strains as well as the probability of first resistance of the DS strain. Key estimates were assessed by the bootstrapping procedure which converged in estimates to the actual data. If the experiment were repeated infinitely many times, in 95 out of 100, the interval 2.782 x 10-7 to 0.018 will contain the true probability of first mutation of the DS strain. A key contribution of this study is the revealing therapeutic cycle of the treatment regime of the TB disease based on the TB progression data which saw the period after the 20th cycle of the treatment being prominent in some key strain dynamics. These findings may also help explain further the pharmacodynamic properties of the "first line" anti-Tuberculosis drugs for enhance TB treatment. Journal of Medical and Biomedical Sciences (2016) 5(2), 13-23

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Definition of drug resistance of Mycobacterium tuberculosis to antituberculosis drugs in patients with multidrugresistant tuberculosis and TB with extremely drug resistant depending on the case of the disease.

Medicni perspektivi (Medical perspectives) ◽

10.26641/2307-0404.2014.4.35801 ◽

2014 ◽

Vol 19 (4) ◽

pp. 84-89

Author(s):

D. G. Kryzhanovsky ◽

N. A. Marchenko ◽

V. A. Freivald

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Drug Resistant ◽

Antituberculosis Drugs ◽

Definition Of

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Susceptibilities of Mycobacterium tuberculosis Complex Isolates to First-line Antituberculosis Drugs at Dokuz Eylül University Hospital

Türk Mikrobiyoloji Cemiyeti Dergisi ◽

10.5222/tmcd.2021.36449 ◽

2021 ◽

Author(s):

Nazlı Arslan ◽

Müge Hacer Özkarataş ◽

Nuran Esen ◽

Aydan Özkütük

Keyword(s):

Mycobacterium Tuberculosis ◽

Mycobacterium Tuberculosis Complex ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

University Hospital ◽

Surveillance Program ◽

Tuberculosis Complex ◽

First Line ◽

Antituberculosis Drugs ◽

Number Of Patients

Objective: Tuberculosis retains its importance as the only infectious disease in the world that affects 10 million people and causes 1.5 million deaths per se. The major obstacle in the elimination and control of tuberculosis is the emergence and spread of resistant tuberculosis cases. It was aimed to determine the current Mycobacterium tuberculosis complex and its susceptibility to antituberculosis drugs at Dokuz Eylül University Hospital. Method: In our study, the results of all samples sent between January 2013 and November 2019 were examined retrospectively for the presence of M. tuberculosis complex and drug susceptibility results. The samples were cultured in Löwenstein Jensen media and BACTEC MGIT 960 system. Drug susceptibility testing was performed with the BACTEC MGIT 960 SIRE kit in accordance with the recommendations of the manufacturer. Results: In a total of 473 (2.2%) of 21620 specimens M. tuberculosis complex was reproduced. The samples were classified as pulmonary (n:300; 63.4%) and extrapulmonary (n:173; 36.6%), samples. When repeated samples of the same patient, were excluded, positive culture test results were determined in a total of 365 patients. Susceptibility to all primary antituberculosis drugs was shown in 275 of 321 (85.7%) patients, while total rates of resistance to streptomycin, isoniazid, rifampicin and ethambutol were found in respective number of patients as follows: (n:24 (7.5%), 22 (6.8%), (n:7; 2.2%) and (n:2; 0.6%). The rate of MDR was 0.6% in 2 patients. Conclusion: In our hospital, streptomycin is the first-line antituberculosis drug with the highest resistance rate. All susceptibility rates were seen lower than the data reported in Turkey Tuberculosis Control Report and other studies of Turkey. Implementing drug surveillance program plays an important role for maintaining these low rates and for the management of tuberculosis.

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