scholarly journals The Synergistic Effects of the Glutathione Precursor, NAC and First-Line Antibiotics in the Granulomatous Response Against Mycobacterium tuberculosis

2018 ◽  
Vol 9 ◽  
Author(s):  
Garrett Teskey ◽  
Ruoqiong Cao ◽  
Hicret Islamoglu ◽  
Albert Medina ◽  
Chaya Prasad ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Synergistic Effects ◽  
First Line ◽  
Granulomatous Response

scholarly journals Characterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of Tuberculosis

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Ruoqiong Cao ◽  
Garrett Teskey ◽  
Hicret Islamoglu ◽  
Rachel Abrahem ◽  
Shalok Munjal ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Synergistic Effects ◽  
Etiological Agent ◽  
Immunomodulatory Effects ◽  
First Line ◽  
Precursor Molecule ◽  
Content Type ◽  
Acetyl Cysteine ◽  
Antioxidant Molecule

ABSTRACT Mycobacterium tuberculosis is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, and the rate of resistance of M. tuberculosis to antibiotics is ever increasing. We tested the synergistic effects of N-acetyl cysteine (NAC; the precursor molecule for the synthesis of glutathione [GSH]) and individual first-line antibiotics typically given for the treatment of TB, such as isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA), to improve the ability of macrophages to control intracellular M. tuberculosis infection. GSH, a pleiotropic antioxidant molecule, has previously been shown to display both antimycobacterial and immune-enhancing effects. Our results indicate that there was not only an increase in beneficial immunomodulatory effects but also a greater reduction in the intracellular viability of M. tuberculosis when macrophages were treated with the combination of antibiotics (INH, RIF, EMB, or PZA) and NAC.

scholarly journals Tuberculous Meningitis: The Microbiological Laboratory Diagnosis and Its Drug Sensitivity Patterns

2019 ◽  
Vol 3 (2) ◽  
pp. 35
Author(s):  
Titiek Sulistyowati ◽  
Deby Kusumaningrum ◽  
Eko Budi Koendhori ◽  
Ni Made Mertaniasih
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculous Meningitis ◽  
Drug Sensitivity ◽  
Mycobacterium Tuberculosis Complex ◽  
Laboratory Diagnosis ◽  
Clinical Microbiology Laboratory ◽  
Tuberculosis Complex ◽  
First Line ◽  
Sensitivity Pattern ◽  
Microbiological Laboratory

Background: Tuberculosis continues one of the major challenges to global health. Mycobacterium tuberculosis complex can affect any organ other than the lung parenchyma, include central nervous system. The mortality rate of tuberculous meningitis (TBM) are high worldwide with up to half of survivors suffering irreversible sequelae. Diagnosis of TBM is difficult due to paucibacillary, various clinical manifestation, and invasive procedure to appropriate specimens. Objective: The objectiveis to study the positivity rate of microbiological laboratory diagnosis and its drug sensitivity patterns of TBM patients in Dr. Soetomo Hospital Surabaya during October 2015 until September 2016. Methods: Specimens were cerebrospinal fluids. Identification and drug anti TB sensitivity test were done by BACTEC MGIT 960 system in Clinical Microbiology Laboratory Dr. Soetomo Hospital Surabaya. Result: Most patients with TBM were women (54.29%). Based on age groups, most dominant was adult population (65.71%). Proportion percentage of positive M. tuberculosis complex among 180 specimens were 19.44%. First line anti TB drug sensitivity pattern of 35 isolates were 1 monoresistant, 1 poly-resistant, no multiple drug resistant (MDR), and 33 pan-susceptible. Conclusion: Positivity rate of Mycobacterium tuberculosis complex laboratory diagnosis from TBM suspect patients were low. There was no MDR TB in this study, but mono-resistant and poly-resistant. Microbiological diagnosis was important to give information of active disease and drug sensitivity pattern. Resistance to first line anti TB drugs is alarming to properly manage TBM patients.

scholarly journals Resistance Patterns of Mycobacterium tuberculosis to First-Line Anti-TB Drugs in Kaduna State, North-Western Nigeria

2020 ◽  
Vol 5 (1) ◽  
pp. 72-76
Author(s):  
M. S Aliyu ◽  
◽  
I. Garba ◽  
M. B. Tijjani ◽  
M. H. I. Doko ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
First Line ◽  
Resistance Patterns ◽  
North Western

Spoligotyping and Drug Sensitivity of Mycobacterium tuberculosis isolated from Pulmonary Tuberculosis Patients in the Arsi Zone of South Eastern Ethiopia

2019 ◽  
Author(s):  
Belete Haile Nega ◽  
Ketema Tafess ◽  
Aboma Zewude ◽  
Bazezew Yenew ◽  
Gilman SIU ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Sensitivity ◽  
Scientific Information ◽  
Rpob Gene ◽  
Drug Susceptibility ◽  
Strain Identification ◽  
First Line ◽  
Eastern Ethiopia ◽  
Arsi Zone ◽  
Mycobacterium Africanum

Abstract Background Tuberculosis (TB) is one of the leading disease causing morbidity and mortality in different zones of Ethiopia including the Arsi Zone. However, little or no scientific information is available on the strains of Mycobacterium tuberculosis and their drug sensitivity profiles in this Zone. This study was conducted to identify the strains of M. tuberculosis and evaluate their drug sensitivity profiles. Methodology A total of 111 clinical isolates of M. tuberculosis from patients with pulmonary TB in the Arsi Zone were used for this study. The region of difference 9 (RD 9)-based polymerase chain reaction (PCR)and spoligotyping methods were used for speciation and strain identification of Mycobacterium tuberculosis respectively.The spoligotyping patterns were compared with the international SpolDB4 (SITVIT) and Run TB-Lineage used for the identification of lineages. The phenotypic drug susceptibility patterns were confirmed by BD BactecMGIT 960 SIRE test and GenoType MTBDRplus line probe assays were used for the detection the drug resistance-conferring mutations of the isolates. Result The spoligotype patterns of 83% (92/111) of the isolates were interpretable and 56 different patterns were identified. Twenty-two of these patterns were shared types while the remaining 34 were orphans. The predominant shared types were spoligotype international type (SIT) 149 and SIT53, each consisting of 12 and 11 isolates, respectively. The lineages identified were Euro-American, East-African-Indian, Mycobacterium-africanum, and Indo-Oceanic in descending order. Phenotypically, 17.2% of the 64 tested isolates were resistant to any of the four first-line drugs while 3.1% of them were multi-drug resistant (MDR). Higher (6.2%) monoresistance was observed to Streptomycin followed by Isoniazid (3.1%) while no resistance was observed either to Rifampicin or to Ethambutol. Genotypically, five (5.4%) isolates were resistant to Isoniazid and mutated at codon S315T1 of katG. On the other hand, only 1.1% of the isolates was resistant to Rifampicin and mutated at codon S531L of rpoB gene. Conclusion The proportion of orphan strains isolated in this study was high, which could suggest the presence of new strains in the Zone. Moreover, the study showed relatively high percentage of mono-resistance to any four first-line drugs warranting for the need to strengthen the control efforts.

scholarly journals A Novel Small-Molecule Inhibitor of the Mycobacterium tuberculosis Demethylmenaquinone Methyltransferase MenG Is Bactericidal to Both Growing and Nutritionally Deprived Persister Cells

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Paridhi Sukheja ◽  
Pradeep Kumar ◽  
Nisha Mittal ◽  
Shao-Gang Li ◽  
Eric Singleton ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Small Molecule ◽  
Drug Target ◽  
High Resolution Mass Spectrometry ◽  
Small Molecule Inhibitor ◽  
First Line ◽  
Respiratory Pathway ◽  
Tb Treatment ◽  
Molecule Inhibitor ◽  
Persistence Model

ABSTRACT Active tuberculosis (TB) and latent Mycobacterium tuberculosis infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating M. tuberculosis “persisters” that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent M. tuberculosis and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors. This screen identified the biphenyl amide GSK1733953A (DG70) as a likely respiration inhibitor. DG70 inhibited both clinical drug-susceptible and drug-resistant M. tuberculosis strains. Whole-genome sequencing of DG70-resistant colonies identified mutations in menG (rv0558), which is responsible for the final step in menaquinone biosynthesis and required for respiration. Overexpression of menG from wild-type and DG70-resistant isolates increased the DG70 MIC by 4× and 8× to 30×, respectively. Radiolabeling and high-resolution mass spectrometry studies confirmed that DG70 inhibited the final step in menaquinone biosynthesis. DG70 also inhibited oxygen utilization and ATP biosynthesis, which was reversed by external menaquinone supplementation. DG70 was bactericidal in actively replicating cultures and in a nutritionally deprived persistence model. DG70 was synergistic with the first-line TB drugs isoniazid, rifampin, and the respiratory inhibitor bedaquiline. The combination of DG70 and isoniazid completely sterilized cultures in the persistence model by day 10. These results suggest that MenG is a good therapeutic target and that compounds targeting MenG along with standard TB therapy have the potential to shorten TB treatment duration. IMPORTANCE This study shows that MenG, which is responsible for the last enzymatic step in menaquinone biosynthesis, may be a good drug target for improving TB treatments. We describe the first small-molecule inhibitor (DG70) of Mycobacterium tuberculosis MenG and show that DG70 has characteristics that are highly desirable for a new antitubercular agent, including bactericidality against both actively growing and nonreplicating mycobacteria and synergy with several first-line drugs that are currently used to treat TB. IMPORTANCE This study shows that MenG, which is responsible for the last enzymatic step in menaquinone biosynthesis, may be a good drug target for improving TB treatments. We describe the first small-molecule inhibitor (DG70) of Mycobacterium tuberculosis MenG and show that DG70 has characteristics that are highly desirable for a new antitubercular agent, including bactericidality against both actively growing and nonreplicating mycobacteria and synergy with several first-line drugs that are currently used to treat TB.

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