scholarly journals Aktivitas Anti-Mycobacterium tuberculosis Kombinasi (-)-Epigallocatechin-Gallate (EGCG) dan Obat Antituberkulosis Lini Pertama

2020 ◽  
pp. 59-66
Author(s):  
Anggita Mirzautika ◽  
Isnaeni Isnaeni ◽  
Djoko Agus Purwanto
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Epigallocatechin Gallate ◽  
Multidrug Resistant ◽  
Dilution Method ◽  
First Line ◽  
Resistant Tuberculosis ◽  
Potentiation Effect ◽  
Before And After ◽  
Tuberculosis Activity

Tuberculosis is a global health problem, and there is even an increase in cases of multidrug-resistant tuberculosis in the world. Therefore, research is needed that can find new anti-tuberculosis drugs (OAT) that are more effective for tuberculosis treatment. In this study, the effect of (-)-epigallocatechin-gallate (EGCG) of tea leaves (Camellia sinensis) combined with the first-line OAT will be observed, in order to find out whether EGCG has anti-tuberculosis activity and can increase the potential of first-line OAT in-vitro. The anti-tuberculosis activity of EGCG was determined by broth dilution method using Middlebrook 7H9 media at concentration of 50, 100, 150, dan 200 ppm, then the potential of first-line OAT before and after combined with the EGCG was observed. The results showed that the activity of EGCG at concentration 50 ppm and 100 ppm could inhibit the Mycobacterium tuberculosis growth by 80%, at concentration 150 ppm by 90%, and at concentration 200 ppm by 100%. First-line OAT activity before combined with EGCG was ≥ 90% at 5 ppm rifampicin, 0.5 ppm isoniazid, 50 ppm pyrazinamide, and 5 ppm ethambutol. Whereas after combined with EGCG, the potential of each drug increased, marked by anti-tuberculosis activity achieved ≥ 90% at lower concentrations, i.e. rifampicin 0.5 ppm, isoniazid 0.25 ppm, pyrazinamide 20 ppm, and ethambutol 2 ppm. These results indicated that the potential of each first-line OAT increases after being combined with EGCG, and EGCG has potentiation effect when combined with those drugs. In conclusion, EGCG can increase the first-line OAT activity

The Potential of Ganoderma Lucidum as Antimicrobial Agent for Multidrug- Resistant Mycobacterium Tuberculosis

2018 ◽  
Vol 16 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Meira Erawati ◽  
Megah Andriany ◽  
Niken Safitri Dyan Kusumaningrum
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Agent ◽  
Ganoderma Lucidum ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background: The problem of bacterial resistance of Mycobacterium tuberculosis should be solved by seeking for alternative substances that potentially inhibit the growth or kill the bacteria. Ganoderma lucidum is one type of fungus which is potential to be an antimicrobial agent. This study aimed to determine the potential of G. lucidum on inhibiting the growth of multidrug-resistant bacteria of M. tuberculosis in vitro. Methods: This study used a solid dilution method to test the extract of G. lucidum as an antibacterial agent. Results and Conclusion: Results showed that all strains of multidrug-resistant tuberculosis (MDR-Tb) gave similar responses to G. lucidum extract at various concentrations. The bacteria did not grow on the medium containing G. lucidum extract at the smallest concentration of 12.5%, as well as concentrations of 25% and 50%. Ganoderma lucidum can be used as one of the alternatives for MDR-Tb drugs in the future.

scholarly journals Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis

2015 ◽  
Vol 59 (9) ◽  
pp. 5844-5846 ◽  
Author(s):  
Sam Ogwang ◽  
Caryn E. Good ◽  
Brenda Okware ◽  
Mary Nsereko ◽  
Michael R. Jacobs ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Pulmonary Tb ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Sub Saharan

ABSTRACTAdditional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to havein vitroactivity againstMycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40Mycobacterium tuberculosisisolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.

scholarly journals Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis

2015 ◽  
Vol 59 (8) ◽  
pp. 4457-4463 ◽  
Author(s):  
Benoit Lechartier ◽  
Stewart T. Cole
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Load ◽  
Multidrug Resistant ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Drug Resistant Strains ◽  
Transfer Chain

ABSTRACTClofazimine (CZM) is an antileprosy drug that was recently repurposed for treatment of multidrug-resistant tuberculosis. InMycobacterium tuberculosis, CZM appears to act as a prodrug, which is reduced by NADH dehydrogenase (NDH-2), to release reactive oxygen species upon reoxidation by O2. CZM presumably competes with menaquinone (MK-4), a key cofactor in the mycobacterial electron transfer chain, for its reduction by NDH-2. We studied the effect of MK-4 supplementation on the activity of CZM againstM. tuberculosisand found direct competition between CZM and MK-4 for the cidal effect of CZM, against nonreplicating and actively growing bacteria, as MK-4 supplementation blocked the drug's activity against nonreplicating bacteria. We demonstrated that CZM, like bedaquiline, is synergisticin vitrowith benzothiazinones such as 2-piperazino-benzothiazinone 169 (PBTZ169), and this synergy also occurs against nonreplicating bacteria. The synergy between CZM and PBTZ169 was lost in an MK-4-rich medium, indicating that MK-4 is the probable link between their activities. The efficacy of the dual combination of CZM and PBTZ169 was testedin vivo, where a great reduction in bacterial load was obtained in a murine model of chronic tuberculosis. Taken together, these data confirm the potential of CZM in association with PBTZ169 as the basis for a new regimen against drug-resistant strains ofM. tuberculosis.

scholarly journals In VitroandIn VivoActivities of the Nitroimidazole TBA-354 against Mycobacterium tuberculosis

2014 ◽  
Vol 59 (1) ◽  
pp. 136-144 ◽  
Author(s):  
A. M. Upton ◽  
S. Cho ◽  
T. J. Yang ◽  
Y. Kim ◽  
Y. Wang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pharmacokinetic Profile ◽  
Multidrug Resistant ◽  
Phase Iii ◽  
Drug Resistant ◽  
Next Generation ◽  
Content Type ◽  
Resistant Tuberculosis

ABSTRACTNitroimidazoles are a promising new class of antitubercular agents. The nitroimidazo-oxazole delamanid (OPC-67683, Deltyba) is in phase III trials for the treatment of multidrug-resistant tuberculosis, while the nitroimidazo-oxazine PA-824 is entering phase III for drug-sensitive and drug-resistant tuberculosis. TBA-354 (SN31354[(S)-2-nitro-6-((6-(4-trifluoromethoxy)phenyl)pyridine-3-yl)methoxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine]) is a pyridine-containing biaryl compound with exceptional efficacy against chronic murine tuberculosis and favorable bioavailability in preliminary rodent studies. It was selected as a potential next-generation antituberculosis nitroimidazole following an extensive medicinal chemistry effort. Here, we further evaluate the pharmacokinetic properties and activity of TBA-354 againstMycobacterium tuberculosis. TBA-354 is narrow spectrum and bactericidalin vitroagainst replicating and nonreplicatingMycobacterium tuberculosis, with potency similar to that of delamanid and greater than that of PA-824. The addition of serum protein or albumin does not significantly alter this activity. TBA-354 maintains activity againstMycobacterium tuberculosisH37Rv isogenic monoresistant strains and clinical drug-sensitive and drug-resistant isolates. Spontaneous resistant mutants appear at a frequency of 3 × 10−7.In vitrostudies andin vivostudies in mice confirm that TBA-354 has high bioavailability and a long elimination half-life.In vitrostudies suggest a low risk of drug-drug interactions. Low-dose aerosol infection models of acute and chronic murine tuberculosis reveal time- and dose-dependentin vivobactericidal activity that is at least as potent as that of delamanid and more potent than that of PA-824. Its superior potency and pharmacokinetic profile that predicts suitability for once-daily oral dosing suggest that TBA-354 be studied further for its potential as a next-generation nitroimidazole.

Structure–activity relationship of natural and synthetic coumarin derivatives against Mycobacterium tuberculosis

2020 ◽  
Vol 12 (17) ◽  
pp. 1533-1546 ◽  
Author(s):  
Claudia TA Pires ◽  
Regiane BL Scodro ◽  
Diógenes AG Cortez ◽  
Mislaine A Brenzan ◽  
Vera LD Siqueira ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Coumarin Derivatives ◽  
Resistant Tuberculosis ◽  
Diphenyltetrazolium Bromide ◽  
Relationship Of ◽  
Microtiter Assay ◽  
Tuberculosis Activity ◽  
Natural And Synthetic

Aim: Eight coumarin derivatives (1a–h) obtained from natural (-)-mammea A/BB (1) and 13 synthetic coumarins (2–14) had their cytotoxicity and biological activity evaluated against Mycobacterium tuberculosis H37Rv reference strain and multidrug-resistant clinical isolates. Materials & methods: Anti- M. tuberculosis activity was evaluated by resazurin microtiter assay plate, and the cytotoxicity of natural and synthetic products using J774A.1 macrophages by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Results: Compounds 1g, 5, 6, 12 and 14 were more active against M. tuberculosis H37Rv and multidrug-resistant clinical isolates with MIC values ranging from 15.6 to 62.5 μg/ml. Conclusion: These results demonstrate that the coumarin derivatives were active against multidrug-resistant clinical isolates, becoming potential candidates to be used in the treatment of resistant tuberculosis.

scholarly journals Toxin-Activating Stapled Peptides Discovered by Structural Analysis Were Identified as New Therapeutic Candidates That Trigger Antibacterial Activity against Mycobacterium tuberculosis in the Mycobacterium smegmatis Model

2021 ◽  
Vol 9 (3) ◽  
pp. 568
Author(s):  
Sung-Min Kang ◽  
Heejo Moon ◽  
Sang-Woo Han ◽  
Byeong Wook Kim ◽  
Do-Hee Kim ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Agents ◽  
Structural Information ◽  
Multidrug Resistant ◽  
Cell Permeability ◽  
Bacterial Cells ◽  
New Era ◽  
Resistant Tuberculosis ◽  
Α Helix

The structure-function relationships of toxin-antitoxin (TA) systems from Mycobacterium tuberculosis have prompted the development of novel and effective antimicrobial agents that selectively target this organism. The artificial activation of toxins by peptide inhibitors can lead to the growth arrest and eventual death of bacterial cells. Optimizing candidate peptides by hydrocarbon α-helix stapling based on structural information from the VapBC TA system and in vitro systematic validation led to V26-SP-8, a VapC26 activator of M. tuberculosis. This compound exhibited highly enhanced activity and cell permeability owing to the stabilizing helical propensity of the peptide. These characteristics will increase its efficacy against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Similar approaches utilizing structural and biochemical information for new antibiotic targets opens a new era for developing TB therapies.

scholarly journals In Vitro Activity of Tetracycline Analogs against Multidrug-resistant and Extensive drug resistance Clinical Isolates of Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Qi Ouyang ◽  
Dachuan Lin ◽  
Guofang Deng ◽  
Zhihua Wen ◽  
Houming Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Underlying Mechanism ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Ammonium Bromide ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has become a big threaten to global health . The current strategy for treatment of MDR-TB and extensive drug resistant tuberculosis (XDR-TB) is with low efficacy and high side effect. While new drug is fundamental for cure MDR-TB, repurposing the Food and Drug Administration (FDA)-approved drugs represents an alternative soluation with less cost.Methods The activity of 8 tetracycline-class antibiotics against mycobacterium tuberculosis ( M.tb ) were determined by Minimum Inhibitory Concentration (MIC) in vitro. A transposon M.smeg libraries was generated by using the Harm phage and then used to isolate the conditional growth mutants in doxycycline containing plate. 11 mutants were isolated and genomic DNAs were extracted using the cetyltrimethyl ammonium bromide (CTAB) method and analyzed by whole genome sequencing.Results We found that three of eight drugs efficiently inhibited mycobacteria growth under the peak plasma concentration in the human body. Further tests showed these three tetracycline analogs (demeclocycline, doxycycline and methacycline) had antimicrobial activity against seven clinical isolates, including MDR and XDR strains. Among them, Doxycycline had the lowest MICs in all mycobacteria strains tested in this study. By using a transposon library, we identify the insertion of transposon in two genes, porin and MshA, associate with the resistant to doxycycline.Conclusions Our findings show that tetracycline analogs such as doxycycline, has bactericidal activity against not only drug sensitive M.tb , but also clinical MDR and XDR strains, provided proof of concept to repurpose doxycycline to fight MDR-TB and XDR-TB. Further investigations are warranted to clarify the underlying mechanism and optimize the strategy in combination with other anti-TB drugs.

scholarly journals Evaluation of <i>In-Vitro</i> Anti-Tuberculosis Activity of <i>Tetrapleura tetraptera</i> Crude and Fractions on Multidrug Resistant <i>Mycobacterium tuberculosis</i>

2020 ◽  
Vol 08 (03) ◽  
pp. 165-176
Author(s):  
Kasim Salihu Izebe ◽  
Kolo Ibrahim ◽  
Josiah Ademola Onaolapo ◽  
Peters Oladosu ◽  
Yakubu Ya’aba ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Tetrapleura Tetraptera ◽  
Tuberculosis Activity

scholarly journals In vitro activities of levofloxacin used alone and in combination with first- and second-line antituberculous drugs against Mycobacterium tuberculosis.

1996 ◽  
Vol 40 (7) ◽  
pp. 1610-1616 ◽  
Author(s):  
N Rastogi ◽  
K S Goh ◽  
A Bryskier ◽  
A Devallois
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Multidrug Resistant ◽  
Second Line ◽  
Tuberculosis Complex ◽  
Complex Type ◽  
First Line ◽  
Antituberculous Drugs ◽  
Strain H37rv

By using the radiometric BACTEC 460-TB methodology, the inhibitory and bactericidal activity of the optically active L-isomer of ofloxacin (levofloxacin) was compared with those of the D-isomer and the commercially available mixture containing equal amounts of DL-isomers (ofloxacin) against the Mycobacterium tuberculosis complex (type strain H37Rv, a panel of drug-susceptible and -resistant clinical isolates including multidrug-resistant isolates of M. tuberculosis, as well as M. africanum, M. bovis, and M. bovis BCG). Levofloxacin MICs (range 0.50 to 0.75 microgram/ml) were about 1 dilution lower than those of ofloxacin (MIC range, 0.75 to 1.00 microgram/ml) and 5 to 6 dilutions lower than those of the D-isomer (MIC range, 32 to 60 micrograms/ml). The MICs of levofloxacin, ofloxacin, and D-ofloxacin at which 90% of the strains are inhibited were 0.50, 1.00, and 64 micrograms/ml, respectively. The multidrug-resistant M. tuberculosis strains resistant to first-line drugs were as susceptible to quinolones as the wild-type drug-susceptible isolates. Levofloxacin at 0.5 microgram/ml showed bactericidal activity comparable to the activities of 1.0 microgram of ofloxacin per ml and 64 micrograms of D-ofloxacin per ml, with MBCs within the range of 0.5 to 2.0 micrograms/ml, compared with MBCs of 0.75 to 4.0 micrograms of ofloxacin per ml for M. tuberculosis, M. africanum, M. bovis BCG. Combination testing of sub-MICs of levolofoxacin with other first-line (isoniazid, rifampin, and ethambutol) and second-line (amikacin and clofazimine) antituberculous drugs was evaluated with various two-, three-, and four-drug combinations; enhanced drug activity was observed in 8 of 25, 12 of 20, and 8 of 15 tests, respectively, indicating that levofloxacin acts in synergy with other antituberculous drugs.

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