Drug Susceptibility of Mycobacterium tuberculosis Through the Mycolic Acid Index

Background:Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date, a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there have been some early drug discovery efforts towards developing potent and selective inhibitors.Objective:Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.Conclusion:Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.

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Comparison of Proportion and Resistance Ratio Methods for Drug Susceptibility Testing of Mycobacterium tuberculosis Isolated from Patients Attending National Tuberculosis Centre, Nepal

SAARC Journal of Tuberculosis Lung Diseases and HIV/AIDS ◽

10.3126/saarctb.v5i1.3078 ◽

2010 ◽

Vol 5 (1) ◽

pp. 13-20

Author(s):

S Acharya ◽

P Ghimire ◽

DK Khadka ◽

S Nepali

Keyword(s):

Mycobacterium Tuberculosis ◽

Fluorescence Microscopy ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Resistance Ratio ◽

National Tuberculosis ◽

Smear Negative ◽

Culture Positive ◽

Good Agreement

Background: Tuberculosis (TB) is among the most serious infectious cause of global morbidity and mortality. Emergence of Multi-drug resistant tuberculosis (MDR-TB) is posing an increased threat to TB control programs. Drug susceptibility testing (DST) of Mycobacterium tuberculosis (M. tuberculosis) isolates is important for tackling such problems. Setting: National Tuberculosis Centre (NTC), Thimi, Bhaktapur, Nepal. Objectives: Comparative evaluation of two in vitro DST methods in determining susceptibility of M. tuberculosis isolates from patients attending NTC, to front-line anti-TB drugs: (Isoniazid-INH, Rifampicin-RFP, Streptomycin-SM, and Ethambutol-EMB). Methodology: This study was conducted from Sep 2006-Jun 2007. A total of 862 sputum samples (diagnosis or follow up cases) collected from patients (type of patients or their categories was not differentiated in this study) attending NTC bacteriology lab for sputum direct smear microscopy were analyzed using fluorescence microscopy. All smear positive samples, smear negative samples requested for culture were cultured. All culture positive samples confirmed as M. tuberculosis by biochemical tests were processed for DST by both proportion (PR) and resistance ratio (RR) methods. Results: Out of 862 sputum samples analyzed, 226 (26.2%) samples were positive for Acid Fast Bacilli (AFB) by fluorescence microscopy. Among 323 samples 226 smear positive samples and 97 smear negative samples requested for culture), 221 (68.4%) were culture positive, 92 (28.5%) were culture negative and 10 (3.1%) were contaminated. Out of 221 isolates of M. tuberculosis, 57.5% were resistant to one or more drugs by the PR method and 56.6% by the RR method. Similarly, MDR isolates were 29.9% and 29% by PR and RR methods respectively. On correlation analysis using Mc Nemar Chi-square test, no significant difference between the two tests were observed (p>0.05). The results showed high agreement between both methods and agreement rates to INH, RFP, SM and EMB were 93.2%, 93.7%, 93.2% and 94.1% respectively. Similarly, the agreement rates between both methods using kappa analysis showed kappa (k) value of 0.86, 0.85, 0.86 and 0.84 for INH, RFP, SM and EMB respectively, which is believed to be good agreement between both methods (k=0.80 to 1.00: Very good agreement). Conclusion: In conclusion, this study showed that both the Proportion and Resistance ratio methods are equally good for determining drug susceptibility of M. tuberculosis. Keywords: Mycobacterium tuberculosis; Drug Susceptibility Testing; Proportion Method; Resistance Ratio Method. DOI: 10.3126/saarctb.v5i1.3078 SAARC J. Tuber. Lung Dis. HIV/AIDS 2008 Vol.5(1) 13-20

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Comparison of the Performances of Two In-House Rapid Methods for Antitubercular Drug Susceptibility Testing

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00960-08 ◽

2008 ◽

Vol 53 (2) ◽

pp. 808-810 ◽

Cited By ~ 6

Author(s):

Agustina I. de la Iglesia ◽

Emma J. Stella ◽

Héctor R. Morbidoni

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Sensitivity And Specificity ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Antitubercular Drug ◽

Rapid Methods ◽

Resistance Assessment

ABSTRACT Resistance to rifampin (rifampicin), isoniazid, and streptomycin of 69 Mycobacterium tuberculosis isolates was analyzed by an in-house method based on mycobacteriophage D29 and a colorimetric micromethod. Both methods showed sensitivity and specificity values ranging from 93% to 100%. These simple methods offer an option for drug resistance assessment of M. tuberculosis.

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Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

Journal of Bacteriology & Parasitology ◽

10.4172/2155-9597.1000e128 ◽

2017 ◽

Vol 09 (01) ◽

Author(s):

Suhail Ahmad

Keyword(s):

Mycobacterium Tuberculosis ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Drug Resistant ◽

First Line ◽

Proper Management ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Polyphosphate Deficiency in Mycobacterium tuberculosis Is Associated with Enhanced Drug Susceptibility and Impaired Growth in Guinea Pigs

Journal of Bacteriology ◽

10.1128/jb.00038-13 ◽

2013 ◽

Vol 195 (12) ◽

pp. 2839-2851 ◽

Cited By ~ 42

Author(s):

R. Singh ◽

M. Singh ◽

G. Arora ◽

S. Kumar ◽

P. Tiwari ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Guinea Pigs ◽

Drug Susceptibility

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Rapid and Inexpensive Drug Susceptibility Testing of Mycobacterium tuberculosis with a Nitrate Reductase Assay

Journal of Clinical Microbiology ◽

10.1128/jcm.40.2.553-555.2002 ◽

2002 ◽

Vol 40 (2) ◽

pp. 553-555 ◽

Cited By ~ 86

Author(s):

K. A. K. Angeby ◽

L. Klintz ◽

S. E. Hoffner

Keyword(s):

Mycobacterium Tuberculosis ◽

Nitrate Reductase ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Nitrate Reductase Assay

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Black Cumin (Nigella sativa) Against Mycobacterium tuberculosis Strain H37RV And MDR-TB

Elkawnie ◽

10.22373/ekw.v7i1.9335 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mashuri Masri ◽

Cut Muthiadin ◽

Masita Masita ◽

Tri Cahyanto ◽

Lianah Lianah ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Multidrug Resistance ◽

Microscopic Observation ◽

Nigella Sativa ◽

Drug Susceptibility ◽

Tuberculosis Strain ◽

Black Cumin ◽

Mdr Tb ◽

Susceptibility Assay ◽

Strain H37rv

Abstract: Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis. 10 million people suffer from TB Every year. Although TB is a preventable and treatable disease, 1.5 million people die every year due to TB. Alternative treatments continue to be pursued, and treatment with the latest TB drugs that are continuously being encouraged. Black cumin (Nigella sativa) seed contains essential oils with active compounds such as thymohydroquinone, Oleoresins, flavonoids, alkaloids, saponins, tannins, and terpenoids that act as antibacterial drugs. This study aims to determine the sensitivity of N. sativa seed extract in inhibiting the growth of M. tuberculosis strain H37RV and MDR-TB (Multidrug Resistance-TB). This research using Microscopic-Observation and Drug-Susceptibility Assay (MODS) method. Extraction of N. sativa was carried out by the maceration method using 70% methanol as a solvent. The results showed that the M. tuberculosis strain H37RV and MDR-TB were sensitive to N. sativa extract at concentrations of 5 and 10% but resistant to N. sativa extract at concentrations of 1 and 3%.Abstrak: Tuberkulosis (TB) adalah penyakit menular yang disebabkan oleh Bakteri Mycobacterium tuberculosis. Penyakit ini menimbulkan dampak kematian yang cukup mengkhawatirkan. Penyakit tersebut dapat dicegah dan diobati. Salah satu sumber pengobatannya menggunakan biji jintan hitam (Nigella sativa) yang mengandung minyak atsiri dengan senyawa aktif seperti timohidrokuinon, oleoresin, flavonoid, alkaloid, saponin, tanin, dan terpenoid yang berfungsi sebagai obat antibakteri. Penelitian ini bertujuan untuk mengetahui sensitivitas ekstrak biji N. sativa dalam menghambat pertumbuhan M. tuberculosis strain H37RV and MDR-TB (Multidrug-Resistance-TB). Penelitian ini menggunakan metode Microscopic-Observation and Drug-Susceptibility Assay (MODS). Ekstraksi N. sativa dilakukan dengan metode maserasi menggunakan pelarut metanol 70%. Hasil yang diperoleh menunjukkan bahwa bakteri M. tuberculosis strain H37RV dan TB-MDR, kedua strain tsb sensitif terhadap ekstrak N. sativa konsentrasi 5 dan 10%, tetapi resisten terhadap ekstrak N. sativa konsentrasi 1 dan 3%.

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