scholarly journals Composition of Three Essential Oils, and their Mammalian Cell Toxicity and Antimycobacterial Activity against Drug Resistant-Tuberculosis and Nontuberculous Mycobacteria Strains

2011 ◽  
Vol 6 (11) ◽  
pp. 1934578X1100601 ◽  
Author(s):  
Juan Bueno ◽  
Patricia Escobar ◽  
Jairo René Martínez ◽  
Sandra Milena Leal ◽  
Elena E. Stashenko
Keyword(s):  
Essential Oils ◽  
Mammalian Cells ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Cell Toxicity ◽  
Epidemic Disease ◽  
Opportunistic Disease ◽  
Turnera Diffusa ◽  
Mdr Tb

Tuberculosis (TB) is the most ancient epidemic disease in the world and a serious opportunistic disease in HIV/AIDS patients. The increase in multidrug resistant Mycobacterium tuberculosis (MDR-TB, XDR-TB) demands the search for novel antimycobacterial drugs. Essential oils (EOs) have been widely used in medicine and some EOs and their major components have been shown to be active against M. tuberculosis. The aim of this work was to evaluate the antimycobacterial and cell toxicity activities of three EOs derived from Salvia aratocensis, Turnera diffusa and Lippia americana, aromatics plants collected in Colombia. The EOs were isolated by hydrodistillation and analyzed by GC/MS techniques. The EOs were tested against 15 Mycobacterium spp using a colorimetric macrodilution method and against mammalian Vero and THP-1 cells by MTT. The activity was expressed as minimal concentration in μg/mL that inhibits growth, and the concentration that is cytotoxic for 50 or 90% of the cells (CC50 and CC90). The major components were epi-α-cadinol (20.1%) and 1,10-di- epi-cubenol (14.2%) for Salvia aratocensis; drima-7,9(11)-diene (22.9%) and viridiflorene (6.6%) for Turnera diffusa; and germacrene D (15.4%) and trans-β- caryophyllene (11.3%) for Lippia americana. The most active EO was obtained from S. aratocensis, with MIC values below 125 μg mL−1 for M. tuberculosis Beijing genotype strains, and 200 to 500 μg mL−1 for nontuberculous mycobacterial strains. The EOs were either partially or non toxic to Vero and THP-1 mammalian cells with CC50 values from 30 to >100 μg mL−1, and a CC90 >100 μg mL−1. The EOs obtained from the three aromatic Colombian plants are an important source of potential compounds against TB. Future studies using the major EO components are recommended.

scholarly journals In Vitro Antimycobacterial Activity of Pakistani Beri Honey Using BACTEC MGIT 960

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Abdul Hannan ◽  
Saira Munir ◽  
Muhammad Usman Arshad ◽  
Nabila Bashir
Keyword(s):  
Growth Control ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Bacterial Disease ◽  
First Line ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Growth Controls

Background. Tuberculosis (TB) is a chronic bacterial disease. Mycobacterium tuberculosis, being the leading member of the MTB complex, is the main cause of tuberculosis worldwide. Tuberculosis is managed with combination of drugs: streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. Over the recent past years resistance against first line antituberculous drugs has emerged rapidly throughout the world resulting in MDR strains. The new threat in the management of MDR-TB is the development of resistance against second line drugs: aminoglycosides, polypeptides, fluoroquinolones, and thioamides. Multidrug resistant (MDR) and extensively drug resistant TB (XDR) strains have become a major concern to control TB particularly in the developing countries. The need of the hour is to look for new modalities having antimycobacterial activity. Honey has been well known for its antibacterial activity. We intended to explore its antimycobacterial activity against MDR-TB. Objective. The objective of this study was to determine whether Pakistani Beri honey has any antimycobacterial activity. Method. The study was conducted in the Department of Microbiology, University of Health Sciences, Lahore. Clinical isolates (n=21) of MDR-MTB were evaluated for their susceptibility to Beri honey. The isolates were provided, courtesy of Pakistan Medical Research Council. These isolates were identified by MTBc ID test (Becton & Dickinson) and further tested for their antimycobacterial activity using Beri honey. The honey was tested at the following concentrations (v/v): 1%, 2%, 3%, 4%, and 5% in MGIT 960. Growth controls were also inoculated with each isolate (growth control has no concentration of honey, only containing growth of isolate). Results. MDR-TB isolates (n=21) were tested; 3 (14%) isolates were susceptible at 1% v/v honey, while at 2% v/v of honey 18 (86%) isolates were found to be susceptible. All the 21 isolates (n=21) were susceptible at 3% v/v of honey. Conclusion. The present study clearly demonstrates that Pakistani Beri honey possesses significant antimycobacterial activity in vitro. The antimycobacterial activity of Pakistani Beri honey may, therefore, be exploited in an appropriate mouse model.

scholarly journals Simple Assay for Detection of the Central Asia Outbreak Clade of theMycobacterium tuberculosisBeijing Genotype

2019 ◽  
Vol 57 (7) ◽  
Author(s):  
Egor Shitikov ◽  
Anna Vyazovaya ◽  
Maja Malakhova ◽  
Andrei Guliaev ◽  
Julia Bespyatykh ◽  
...  
Keyword(s):  
Soviet Union ◽  
Molecular Marker ◽  
Central Asia ◽  
Former Soviet Union ◽  
Multidrug Resistant ◽  
Rapid Screening ◽  
Beijing Genotype ◽  
Data Set ◽  
Content Type ◽  
Mdr Tb

ABSTRACTThe Central Asia outbreak (CAO) clade is a branch of theMycobacterium tuberculosisBeijing genotype that is associated with multidrug resistance, increased transmissibility, and epidemic spread in parts of the former Soviet Union. Furthermore, migration flows bring these strains far beyond their areas of origin. We aimed to find a specific molecular marker of the Beijing CAO clade and develop a simple and affordable method for its detection. Based on the bioinformatics analysis of the largeM. tuberculosiswhole-genome sequencing (WGS) data set (n = 1,398), we identified an IS6110insertion in theRv1359-Rv1360intergenic region as a specific molecular marker of the CAO clade. We further designed and optimized a multiplex PCR method to detect this insertion. The method was validatedin silicowith the recently published WGS data set from Central Asia (n = 277) and experimentally withM. tuberculosisisolates from European and Asian parts of Russia, the former Soviet Union, and East Asia (n = 319). The developed molecular assay may be recommended for rapid screening of retrospective collections and for prospective surveillance when comprehensive but expensive WGS is not available or practical. The assay may be especially useful in high multidrug-resistant tuberculosis (MDR-TB) burden countries of the former Soviet Union and in countries with respective immigrant communities.

scholarly journals Antimycobacterial Activity of the Extract and Isolated Compounds From the Stem Bark of Zanthoxylum leprieurii Guill. and Perr.

2021 ◽  
Vol 16 (8) ◽  
pp. 1934578X2110358
Author(s):  
Benson Oloya ◽  
Jane Namukobe ◽  
Matthias Heydenreich ◽  
Willy Ssengooba ◽  
Bernd Schmidt ◽  
...  
Keyword(s):  
Antimycobacterial Activity ◽  
Stem Bark ◽  
Multidrug Resistant ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
Minimum Inhibitory Concentrations ◽  
Mdr Tb ◽  
Weak Activity ◽  
First Time ◽  
Chloroform Methanol

Zanthoxylum leprieurii Guill. and Perr. (Rutaceae) stem bark is used locally in Uganda for treating tuberculosis (TB) and cough-related infections. Lupeol (1), sesamin (2), trans-fagaramide (3), arnottianamide (4), ( S)-marmesinin (5), and hesperidin (6) were isolated from the chloroform/methanol (1:1) extract of Z. leprieurii stem bark. Their structures were elucidated using spectroscopic techniques and by comparison with literature data. Furthermore, the extract and isolated compounds were subjected to antimycobacterial activity. The extract exhibited moderate activity against the susceptible (H37Rv) TB strain, but weak activity against the multidrug resistant (MDR)-TB strain with minimum inhibitory concentrations (MICs) of 586.0 and 1172.0 μg/mL, respectively. Compound 3 (trans-fagaramide) showed significant antimycobacterial activity against the susceptible (H37Rv) TB strain (MIC 6 μg/mL), but moderate activity against the MDR-TB strain (MIC 12.2 μg/mL). Compounds 2, 5, 6, and 1 showed moderate activities against the susceptible (H37Rv) strain (MIC 12.2-98.0 μg/mL) and moderate to weak activities against the MDR-TB strain (MIC 24.4-195.0 μg/mL). This study reports for the first time the isolation of compounds 1 to 6 from the stem bark of Z leprieurii. trans-Fagaramide (3) may present a vital template in pursuit of novel and highly effective TB drugs.

scholarly journals Bedaquiline for multidrug-resistant TB in paediatric patients

2021 ◽  
Vol 25 (9) ◽  
pp. 716-724
Author(s):  
R. Moodliar ◽  
V. Aksenova ◽  
M. V. G. Frias ◽  
J. van de Logt ◽  
S. Rossenu ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Area Under The Curve ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Dose Selection ◽  
Primary Analysis ◽  
Open Label ◽  
Target Values ◽  
Mdr Tb ◽  
Age Appropriate

BACKGROUND: TMC207-C211 (NCT02354014) is a Phase 2, open-label, multicentre, single-arm study to evaluate pharmacokinetics, safety/tolerability, antimycobacterial activity and dose selection of bedaquiline (BDQ) in children (birth to <18 years) with multidrug-resistant-TB (MDR-TB).METHODS: Patients received 24 weeks’ BDQ with an anti-MDR-TB background regimen (BR), followed by 96 weeks of safety follow-up. Results of the primary analysis are presented based on data up to 24 weeks for Cohort 1 (≥12–<18 years; approved adult tablet at the adult dosage) and Cohort 2 (≥5–<12 years; age-appropriate 20 mg tablet at half the adult dosage).RESULTS: Both cohorts had 15 patients, of whom respectively 53% and 40% of Cohort 1 and Cohort 2 children had confirmed/probable pulmonary MDR-TB. Most patients completed 24 weeks´ BDQ/BR treatment (Cohort 1: 93%; Cohort 2: 67%). Geometric mean BDQ area under the curve 168h values of 119,000 ng.h/mL (Cohort 1) and 118,000 ng.h/mL (Cohort 2) at Week 12 were within 60–140% (86,200–201,000 ng.h/mL) of adult target values. Few adverse event (AE) related discontinuations or serious AEs, and no QTcF >460 ms during BDQ/BR treatment or deaths occurred. Of MGIT-evaluable patients, 6/8 (75%) Cohort 1 and 3/3 (100%) Cohort 2 culture converted.CONCLUSION: In children and adolescents aged ≥5–<18 years with MDR-TB, including pre-extensively drug-resistant-TB (pre-XDR-TB) or XDR-TB, 24 weeks of BDQ provided a comparable pharmacokinetic and safety profile to adults.

scholarly journals Targeting the trehalose utilization pathways ofMycobacterium tuberculosis

MedChemComm ◽  
2016 ◽  
Vol 7 (1) ◽  
pp. 69-85 ◽  
Author(s):  
Sandeep Thanna ◽  
Steven J. Sucheck
Keyword(s):  
World Wide ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Epidemic Disease ◽  
Ofmycobacterium Tuberculosis ◽  
Mdr Tb

Tuberculosis (TB) is an epidemic disease and the growing burden of multidrug-resistant (MDR) TB world wide underlines the need to discover new drugs to treat the disease.

scholarly journals Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Noura M. Al-Mutairi ◽  
Suhail Ahmad ◽  
Eiman M. Mokaddas
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phylogenetic Tree ◽  
Sequence Data ◽  
Regulatory Region ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Mdr Tb ◽  
Low Incidence ◽  
Local Transmission

Abstract Background Increasing incidence of multidrug-resistant Mycobacterium tuberculosis infections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~ 1% of M. tuberculosis strains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait. Methods Ninety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplus assay and/or PCR sequencing of three rpoB regions, katG codon 315 (katG315) + inhA regulatory region, pncA, three embB regions and rpsL + rrs-500–900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing of gidB and rpsA was performed for cluster isolates. Results Pansusceptible isolates contained wild-type sequences. Mutations in rpoB and katG and/or inhA were detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates in pncA, embB and rpsL + rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additional gidB and rpsA sequence data. Conclusions Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2–6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.

scholarly journals First insight into the genotype and molecular epidemiology of MDR-TB isolates from Chongqing Municipality of China using 24-loci MIRU-VNTR technique

2019 ◽  
Author(s):  
Lei Xu ◽  
Yan Hu ◽  
Tongxin Li ◽  
Chun Yang ◽  
Yonglin He ◽  
...  
Keyword(s):  
Variable Number Tandem Repeat ◽  
Melting Curve ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Beijing Genotype ◽  
Molecular Characteristics ◽  
Chongqing Municipality ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
High Discriminatory Power

Abstract Background: Multidrug-resistant tuberculosis (MDR-TB) has become a great threat to TB control around the world. In 2017, there were 889,000 new tuberculosis cases in China, and 31.1% were MDR/RR-TB (TB resistant to rifampicin). This study aims to explore the the molecular characteristics and factors associated with infection among different genotype MDR strains in Chongqing, China. Methods: All the 230 MDR-TB isolates were genotyped using 24-loci mycobacterial interspersed repetitive unite variable number tandem repeat (MIRU-VNTR) method and multiplex real-time PCR melting curve assay of Rv2952 gene and mutT2 gene. Polymorphism and clustering analysis of each locus was carried out by BioNumerics Version 5.0. Results: By genotyping, 83.0% (191/230) of the MDR-TB isolates were Beijing strains, among which 41.9% from the ancient Beijing genotype and 58.1% from the modern Beijing genotype. Based on 24-loci, the 230 MDR isolates were classified into 208 genotypes, among which 38 isolates belonged to 16 clusters. The clustering rate was 16.5%. The percentages of SM-resistant and EMB-resistant in Beijing genotype were significantly higher than those in non-Beijing genotype (P < 0.01). The Beijing genotype had a significantly high risk to be clustered than non-Beijing genotype (p < 0.01). The percentages of SM-resistant isolates in clustered group were significantly higher than non-clustered group (P < 0.01). According to 24-loci, the HGDI was 0.9988, and five loci (Qub11b, Qub26, Mtub21, MIRU26, Mtub04) have high discriminatory power (HGDI > 0.6), while 7 loci (MIRU4, MIRU23, Mtub34, MIRU20, Mtub29, MIRU2, MIRU24) showed negligible diversity (HGDI < 0.1). The percentage of clustered rate showed no difference between 24-loci and 15-loci (p = 0.19). Conclusion: Among MDR isolates in Chongqing China, Beijing genotype is more likely to be drug resistant and clustered, and SM-resistant isolates are more likely to be clustered that may related to the MDR epidemic. Although 24-loci had a high resolution of genotype, some new loci should be found to replace the poor diversity loci in 24-loci and additional analysis of specific sublineage of Beijing genotype is needed in order to better understand the relations between the molecular characteristics of strains and MDR-TB epidemic.

scholarly journals Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hui Xia ◽  
Susan van den Hof ◽  
Frank Cobelens ◽  
Yang Zhou ◽  
Bing Zhao ◽  
...  
Keyword(s):  
Hot Spot ◽  
Scale Up ◽  
Point Mutations ◽  
Previous Treatment ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
Beijing Genotype ◽  
Molecular Testing ◽  
Mdr Tb

Abstract Background Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations. Methods MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression. Results Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34–0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified. Conclusions Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability .

scholarly journals MOLECULAR EPIDEMIOLOGY OF MULTIDRUG RESISTANT TUBERCULOSIS IN MONGOLIA AND EASTERN SIBERIA: TWO INDEPENDENT DISSEMINATION PROCESSES FOR DOMINANT STRAINS

2019 ◽  
Author(s):  
S. Zhdanova ◽  
M. Badleeva ◽  
O. Ogarkov ◽  
E. Orlova
Keyword(s):  
Hiv Infection ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Eastern Siberia ◽  
Cross Border ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Wide Range ◽  
Mdr Tb ◽  
The Cross

Mongolia and Russia are among the countries with the high tuberculosis (TB) burden. The prevalence of tuberculosis, including multidrug-resistant tuberculosis (MDR), in Eastern Siberia bordering Mongolia is significantly higher than that of in the European part of Russia. In addition, unlike Mongolia, Eastern Siberia is characterized by a high prevalence of HIV infection. The cross-border spread of socially significant infections in these countries seems to be occur due to their wide-range cooperation and cultural exchange. Whereas the HIV infection has no epidemiological significance for Mongolia at the moment, tuberculosis, however, on both sides of the border has a similar prevalence. The aim was to evaluate the cross-border MDR M. tuberculosis distribution in Mongolia and Eastern Siberia by using molecular genetic data.Materials and methods: A total of 1045 M. tuberculosis strains isolated in Mongolia (291) and the three regions of Eastern Siberia (754) were studied by using the MIRU-VNTR - 24 loci genotyping. The CC2/W148 and CC1 subtype was identified by the specific deletion in the kdpD gene and SNP in the pks17 gene at position 1887060, respectively.Phylogenetic analysis of MIRU-VNTR patterns was carried out by generating UPGMA tree and maximum likelihood tree. Results. The Beijing genotype was found in 75.3% (219/291) and 69.0% (520/754) from Mongolian and East Siberian collect ion, respectively. Common minor genotypes were LAM (11.0% and 15.1%), T (10.3% and 4.5%), Haarlem (1.4% and 2.4%) found in Mongolia and Eastern Siberia, respectively. The genotype S (1.3%) and Ural (5.0%) was found solely in the Russia-derived samples. The main epidemic Beijing subtypes in each country belonged to different clonal complexes (CC): the majority of Mongolian Beijing strains displayed profiles 342-32, 3819-32, 1773-32 MLVA types and belonged to the CC4 subtype; Russian Beijing strains mainly belonged to the CC1 (43.7% - 227/520) and CC2/W148 (34.8% - 181/520) subtypes.The MDR level and distribution patterns differed significantly between Mongolia and Eastern Siberia. Modeling of Beijing strain expansion evidences about extremely subtle contribution of the M. tuberculosis cross-border transmission between Mongolia and Russia. The phylogenetic reconstruction of Beijing CC4 subtype evolution in Mongolia suggests that its distribution is primarily associated with China and other countries of the West Pacific region. Three main phylogenetic branches of CC4 subtype were traced, which probably spread throughout Mongolia in the 11-12th centuries. It may be assumed that spread of the epidemic Beijing CC4 subtype might occur in two stages: early period – emergence of ancestral CC4 variants in Mongolia or their introduction from China (they are homologous to the strains preserved in the Chinese population); later period – dissemination due to the active exchange of M. tuberculosis with countries of Southeast Asia, but not Russia.Conclusion. Using MIRU-VNTR 24 genotyping as well as classification according to specific single nucleotide polymorphisms specific to certain Beijing subtypes, it allowed to describe separate patterns of the epidemic variants spread in Mongolia and Russia. It has been demonstrated that emergence and spread of MDR-TB in Mongolia is entirely iatrogenic in nature, while the epidemic subtypes of the Beijing genotype (subtypes CC1 and CC2 / W148) contribute markedly into the MDR-TB spread in Eastern Siberia.

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