Mycobacterium tuberculosis strains isolated from Van region four different sensitivity detection method antimycobacterial agents

Mycobacterium tuberculosis (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb’s cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4′-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction. Thus, loss-of-function mutants of PptH displayed antimicrobial resistance. Our PptT-inhibitor cocrystal structure may aid further development of antimycobacterial agents against this long-sought target. The opposing reactions of PptT and PptH uncover a regulatory pathway in CoA physiology.

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Detection of Mycobacterium tuberculosis based on H37Rv binding peptides using surface functionalized magnetic microspheres coupled with quantum dots – a nano detection method for Mycobacterium tuberculosis

International Journal of Nanomedicine ◽

10.2147/ijn.s71700 ◽

2014 ◽

pp. 77 ◽

Cited By ~ 61

Author(s):

Hua Yang ◽

Lianhua Qin ◽

Yilong Wang ◽

Bingbo Zhang ◽

Zhonghua Liu ◽

...

Keyword(s):

Quantum Dots ◽

Mycobacterium Tuberculosis ◽

Detection Method ◽

Magnetic Microspheres ◽

Binding Peptides

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Postantibiotic Effects of Antituberculosis Agents Alone and in Combination

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.12.3631-3634.2001 ◽

2001 ◽

Vol 45 (12) ◽

pp. 3631-3634 ◽

Cited By ~ 18

Author(s):

Chiu-Yeung Chan ◽

Carrie Au-Yeang ◽

Wing-Wai Yew ◽

Mamie Hui ◽

Augustine F. B. Cheng

Keyword(s):

Mycobacterium Tuberculosis ◽

Culture System ◽

Scientific Basis ◽

Viable Count ◽

First Line ◽

Count Method ◽

Antimycobacterial Agents ◽

Antituberculosis Chemotherapy

ABSTRACT The postantibiotic effects (PAEs) of seven antimycobacterial agents, tested at their respective peak concentrations in serum alone and in different combinations, against Mycobacterium tuberculosis ATCC 27294 were studied with a radiometric culture system in parallel with the viable count method. Rifampin gave the longest PAE (67.8 h) among the drugs used alone, and combinations of first-line drugs generally gave PAEs longer than 120 h. The data obtained might help provide a better understanding of the scientific basis of intermittently administered antituberculosis chemotherapy.

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Susceptibility of Mycobacterium tuberculosis to first-line antimycobacterial agents in a Brazilian hospital: assessing the utility of the tetrazolium (MTT) microplate assay

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02762010000500010 ◽

2010 ◽

Vol 105 (5) ◽

pp. 661-664 ◽

Cited By ~ 1

Author(s):

Michela De Luca Ferrari ◽

Maria Alice da Silva Telles ◽

Lucilaine Ferrazoli ◽

Carlos Emílio Levy ◽

Maria Cecília Barison Villares ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Microplate Assay ◽

First Line ◽

Antimycobacterial Agents

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SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF PIPERIDINE AND MORPHOLINE 1, 8 NAPHTHYRIDINE ANALOGUES

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.13503 ◽

2016 ◽

Vol 8 (12) ◽

pp. 252 ◽

Cited By ~ 2

Author(s):

Muwaffag Badawneh ◽

Jalal Aljamal

Keyword(s):

Mycobacterium Tuberculosis ◽

Inhibitory Concentration ◽

Antitubercular Activity ◽

Antimycobacterial Activity ◽

Significant Activity ◽

Reference Drug ◽

Novel Drugs ◽

Elemental Analyses ◽

Antimycobacterial Agents

Objective: The search for new, potentially useful antimycobacterial agents. In continuation with our previous screening for the discovery of novel drugs for tuberculosis, a new series of 1,8-naphthyridines derivatives were synthesized and evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis H37Rv.Methods: Several 4-morpholinomethyl-1.8-naphthyridine derivatives have been synthesized in excellent yields. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimycobacterial activity. The growth was monitored radiometrically in 7H12 broth with the BACTEC 460 TB system. The minimum inhibitory concentration (MIC) was determined for compounds that demonstrated ≥ 90% growth inhibition in the primary screening.Results: The obtained data suggested that all compounds showed significant activity against Mycobacterium tuberculosis H37Rv compared to the standard reference drug. Analogues (6-11) having heterocyclic groups in position 7 were the most potent of those we tested.Conclusion: These findings clearly identify the 1,8-naphthyridine analogue (10) with a 6-amino-2-(4'-methoxy benzylamine-4-morpholinomethyl-7-morpholino-substituent as promising anti-tubercular agents possessing significant activity against Mycobacterium tuberculosis H37Rv

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Study on N-(pyridin-4-Yl) Salicylamides as Antimycobacterial Agents

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.634-638.1371 ◽

2013 ◽

Vol 634-638 ◽

pp. 1371-1375

Author(s):

Zhi Jun Xin ◽

Zhong Jia ◽

Dian He ◽

Jian Ping Liang ◽

Lei Tao ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Mycobacterium Avium ◽

Substituent Effect ◽

Pyridine Ring ◽

Wide Spectrum ◽

Minimum Inhibitory Concentrations ◽

Antimycobacterial Agents

A series of N-(pyridin-4-yl) salicylamides derivatives were prepared through acylation of the corresponding acetylsalicyloyl chlorides with substituted 4-amino-pyridines. These compounds were evaluated in vitro for antimycobacterial activities against Mycobacterium tuberculosis (TB) and Mycobacterium avium (A) by the minimum inhibitory concentrations (MIC) values. Eight of the compounds exhibited lower MIC against A than isoniazide (INH). Meanwhile, four of the compounds exhibited good anti-TB activity, when they were compared with INH. Antimycobacterial activities of N-(pyridin-4-yl) salicylamides were influenced by the balance between hydrophobicity and electron-withdrawing substituent effect on the phenyl and pyridine ring. These studies show that these compounds might serve as prospective wide-spectrum antimycobacterial substances.

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Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis

Annals of Clinical Microbiology and Antimicrobials ◽

10.1186/s12941-021-00478-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mao Ye ◽

Wen Yuan ◽

Leila Molaeipour ◽

Khalil Azizian ◽

Alireza Ahmadi ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Subgroup Analysis ◽

Detection Method ◽

Meta Analysis ◽

Resistance Development ◽

Pooled Prevalence ◽

Important Trend ◽

Reliable Methods ◽

Selection Of

Abstract Background Mycobacterium tuberculosis (MTB) is responsible for tuberculosis; that continues to be a public health threat across the globe. Furthermore, increasing heteroresistance (HR)-the presence of resistant and susceptible isolates among MTB strains- has been reported from around the world. This phenomenon can lead to full resistance development and treatment failure. Methods We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until October 21, 2020). The study outcomes revealed the weighted pooled prevalence of antibiotic HR in MTB isolates with subgroup analysis by year, quality of study, and heteroresistance detection method. Results A total of 38 studies which had investigated MTB isolates were included in the meta-analysis. Geographically, the highest number of studies were reported from Asia (n = 24), followed by Africa (n = 5). Nineteen studies reported HR to isoniazid, with a weighted pooled prevalence of 5% (95% CI 0–12) among 11,761 MTB isolates. Also, there is no important trend for the subgroup analysis by the study period (2001–2014 vs 2015–2017 vs 2018–2020). HR to rifampin was reported in 17 studies, with a weighted pooled prevalence of 7% (95% CI 2–14) among 3782 MTB isolates. HR to fluoroquinolone and ethambutol were reported in 12 and 4 studies, respectively, with weighted pooled prevalence of 10% and 1% among 2153 and 1509 MTB isolates, correspondingly. Conclusion Based on our analysis, HR in MTB isolates with different frequency rate is present worldwide. Thus, the selection of appropriate and reliable methods for HR detection is crucial for TB eradication.

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Synthesis of Antimycobacterial Agents that Harness Mycothiol and Cysteine conjugate β-lyase Metabolic Pathways

10.26686/wgtn.17018843 ◽

2021 ◽

Author(s):

◽

Scott W. Riordan

Keyword(s):

Mycobacterium Tuberculosis ◽

Mycobacterium Smegmatis ◽

Antimycobacterial Activity ◽

New Drugs ◽

Bacillus Calmette Guerin ◽

Antimycobacterial Agents ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Related Compounds ◽

Synthetic Target

Mycobacterium tuberculosis kills approximately two million people each year and is second only to HIV/AIDs in terms of death from infectious disease. The most pertinent problem in regards to Mycobacterium tuberculosis today is the increasing prevalence of drug resistant strains. Thus, there is a great need for the development of new drugs with novel targets. This thesis aimed to address this problem by synthesizing a compound that could exploit the mycothiol detoxification pathway, unique to Mycobacterium, in order to cause cell death, through the release of a harmful halothioketene. The research described herein involved the successful synthesis of the desired mycothiol analogue, along with three other related compounds. The target compounds were synthesised via protection of N-acetyl glucosamine, followed by thioglycosidation with cyclohexane thiol. Subsequent deprotection and coupling to Boc protected Strichlorovinyl cysteine provided access to the synthetic target and its β-anomer, as well as their Boc protected precursors. The original synthetic target demonstrated weak antimycobacterial activity against Mycobacterium smegmatis and an encouraging sub 100 μM MIC against Mycobacterium bovis derived Bacillus Calmette–Guérin. Unexpectedly the beta anomer of the synthetic target also displayed antimycobacterial activity against Bacillus Calmette–Guérin (MIC 125 - 250 μM). All compounds proved to be active against HL60 cells (16-114 μM). Whilst further work is required to improve efficacy, the work presented here demonstrates the potential of these compounds as leads for the generation of new antimycobacterial agents.

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