scholarly journals The Use of Functional Genomics in Conjunction with Metabolomics forMycobacterium tuberculosisResearch

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Conrad C. Swanepoel ◽  
Du Toit Loots
Keyword(s):  
Infectious Disease ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Systems Biology ◽  
Functional Genomics ◽  
The Past ◽  
Holistic Understanding ◽  
Transcriptomics Data ◽  
Genomic Studies ◽  
Complex Genome

Tuberculosis (TB), caused byMycobacterium tuberculosis, is a fatal infectious disease, resulting in 1.4 million deaths globally per annum. Over the past three decades, genomic studies have been conducted in an attempt to elucidate the functionality of the genome of the pathogen. However, many aspects of this complex genome remain largely unexplored, as approaches like genomics, proteomics, and transcriptomics have failed to characterize them successfully. In turn, metabolomics, which is relatively new to the “omics” revolution, has shown great potential for investigating biological systems or their modifications. Furthermore, when these data are interpreted in combination with previously acquired genomics, proteomics and transcriptomics data, using what is termed a systems biology approach, a more holistic understanding of these systems can be achieved. In this review we discuss how metabolomics has contributed so far to characterizing TB, with emphasis on the resulting improved elucidation ofM. tuberculosisin terms of (1) metabolism, (2) growth and replication, (3) pathogenicity, and (4) drug resistance, from the perspective of systems biology.

Drug Resistance of Mycobacterium Tuberculosis in Karachi, Pakistan

1993 ◽  
Vol 23 (1) ◽  
pp. 13-14 ◽  
Author(s):  
Javaid Khan ◽  
Najmul Islam ◽  
Nadya Ajanee ◽  
Wasim Jafri
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Previous Treatment ◽  
Tuberculosis Treatment ◽  
Primary Resistance ◽  
Secondary Resistance ◽  
The Past ◽  
History Of ◽  
And Control

We determined the primary and secondary resistance of isolates of M. tuberculosis to the standard anti-tuberculous drugs in Karachi (Pakistan). Primary resistance to one or more anti-tuberculous drugs was found in 17% of 123 isolates of M. tuberculosis (obtained from patients with no history of previous treatment for tuberculosis). Secondary resistance was found in 36% of 33 isolates (obtained from individuals who had received anti-tuberculous treatment in the past). The drug to which organisms were most commonly resistant was isoniazid (11% primary resistance, 30% secondary resistance). Fifteen per cent of isolates obtained from previously-studied patients showed secondary resistance to rifampicin. We discuss the importance of these findings for tuberculosis treatment and control.

scholarly journals The Inhibition of Folylpolyglutamate Synthetase (folC) in the Prevention of Drug Resistance inMycobacterium tuberculosisby Traditional Chinese Medicine

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Tzu-Chieh Hung ◽  
Kuen-Bao Chen ◽  
Wen-Yuan Lee ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Infectious Disease ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Structural Variation ◽  
Structural Variations ◽  
Ligand Interaction ◽  
Folylpolyglutamate Synthetase ◽  
Protein Ligand Interaction

Tuberculosis (TB) is an infectious disease caused by many strains of mycobacteria, but commonlyMycobacterium tuberculosis. As a possible method of reducing the drug resistance ofM. tuberculosis, this research investigates the inhibition of Folylpolyglutamate synthetase, a protein transcript from the resistance association gene folC. After molecular docking to screen the traditional Chinese medicine (TCM) database, the candidate TCM compounds, with Folylpolyglutamate synthetase, were selected by molecular dynamics. The 10,000 ps simulation in association with RMSD analysis and total energy and structural variation defined the protein-ligand interaction. The selected TCM compounds Saussureamine C, methyl 3-O-feruloylquinate, and Labiatic acid have been found to inhibit the activity of bacteria and viruses and to regulate immunity. We also suggest the possible pathway in protein for each ligand. Compared with the control, similar interactions and structural variations indicate that these compounds might have an effect on Folylpolyglutamate synthetase. Finally, we suggest Saussureamine C is the best candidate compound as the complex has a high score, maintains its structural composition, and has a larger variation value than the control, thus inhibiting the drug resistance ability ofMycobacterium tuberculosis.

scholarly journals The Combination of Sulfamethoxazole, Trimethoprim, and Isoniazid or Rifampin Is Bactericidal and Prevents the Emergence of Drug Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 56 (10) ◽  
pp. 5142-5148 ◽  
Author(s):  
Catherine Vilchèze ◽  
William R. Jacobs
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Drug Resistant ◽  
Content Type ◽  
The Past ◽  
Tb Treatment

ABSTRACTThe challenges of developing new drugs to treat tuberculosis (TB) are indicated by the relatively small number of candidates entering clinical trials in the past decade. To overcome these issues, we reexamined two FDA-approved antibacterial drugs, sulfamethoxazole (SMX) and trimethoprim (TMP), for use in TB treatment. SMX and TMP inhibit folic acid biosynthesis and are used in combination to treat infections of the respiratory, urinary, and gastrointestinal tracts. The MICs of SMX and TMP, alone and in combination, were determined for drug-susceptible, multidrug-resistant (MDR), and extensively drug-resistantMycobacterium tuberculosisstrains. While TMP alone was not effective againstM. tuberculosis, the combination of TMP and SMX was bacteriostatic againstM. tuberculosis. Surprisingly, the combination of SMX and TMP was also active against a subset of MDRM. tuberculosisstrains. Treatment ofM. tuberculosiswith TMP-SMX and a first-line anti-TB drug, either isoniazid or rifampin, was bactericidal, demonstrating that the combination of TMP and SMX with isoniazid or rifampin was not antagonistic. Moreover, the addition of SMX-TMP in combination with either isoniazid or rifampin also prevented the emergence of drug resistancein vitro. In conclusion, this study further illustrates the opportunity to reevaluate the activity of TMP-SMXin vivoto prevent the emergence of drug-resistantM. tuberculosis.

scholarly journals THE EPIDEMIOLOGICAL SITUATION AND A TREND IN THE DRUG RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS IN THE SMOLENSK REGION IN 2005-2010

2012 ◽  
Vol 17 (1) ◽  
pp. 4-9
Author(s):  
T. V. Myakisheva ◽  
M. A. Gudenkov
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multidrug Resistance ◽  
The Past ◽  
Healthcare Network ◽  
Epidemiological Situation

The tuberculosis epidemiological situation in the Smolensk Region in 2005-2010 was appraised as poor and more tense than that in Russia as a whole. Its deterioration was noted in terms of most indicators in the past 6 years. The general healthcare network facilities were found to inadequately detect patients with tuberculosis particularly with fluorographic methods. There was a change in the pattern of drug resistance in Mycobacterium tuberculosis in the region, a decrease in monoresistance, an increase in multidrug resistance, and preservation high of polyresistance.

scholarly journals Reprogramming the endogenous type III-A CRISPR-Cas system for genome editing, RNA interference and CRISPRi screening in Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Khaista Rahman ◽  
Muhammad Jamal ◽  
Xi Chen ◽  
Wei Zhou ◽  
Bin Yang ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Rna Interference ◽  
Functional Genomics ◽  
Genome Editing ◽  
Antibiotics Resistance ◽  
Screening Methods ◽  
Crispr Interference ◽  
Type Iii ◽  
Genome Wide

AbstractMycobacterium tuberculosis (M.tb) causes the current leading infectious disease. Examination of the functional genomics of M.tb and development of drugs and vaccines are hampered by the complicated and time-consuming genetic manipulation techniques for M.tb. Here, we reprogrammed M.tb endogenous type III-A CRISPR-Cas10 system for simple and efficient gene editing, RNA interference and screening via simple delivery of a plasmid harboring a mini-CRISPR array, thereby avoiding the introduction of exogenous proteins and minimizing proteotoxicity. We demonstrated that M.tb genes were efficiently and specifically knocked-in/out by this system, which was confirmed by whole-genome sequencing. This system was further employed for single and simultaneous multiple-gene RNA interference. Moreover, we successfully applied this system for genome-wide CRISPR interference screening to identify the in-vitro and intracellular growth-regulating genes. This system can be extensively used to explore the functional genomics of M.tb and facilitate the development of new anti-Mycobacterial drugs and vaccines.SummaryTuberculosis caused by Mycobacterium tuberculosis (M.tb) is the current leading infectious disease affecting more than ten million people annually. To dissect the functional genomics and understand its virulence, persistence, and antibiotics resistance, a powerful genome editing tool and high-throughput screening methods are desperately wanted. Our study developed an efficient and a robust tool for genome editing and RNA interference in M.tb using its endogenous CRISPR cas10 system. Moreover, the system has been successfully applied for genome-wide CRISPR interference screening. This tool could be employed to explore the functional genomics of M.tb and facilitate the development of anti-M.tb drugs and vaccines.

scholarly journals Drug-resistance inMycobacterium tuberculosis: where we stand

MedChemComm ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 1342-1360 ◽  
Author(s):  
Amanda Mabhula ◽  
Vinayak Singh
Keyword(s):  
Infectious Disease ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Vulnerable Populations

Tuberculosis (TB), an infectious disease caused by the bacteriumMycobacterium tuberculosis(Mtb), has burdened vulnerable populations in modern day societies for decades.

scholarly journals A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

mBio ◽  
2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Alan Aderem ◽  
Joshua N. Adkins ◽  
Charles Ansong ◽  
James Galagan ◽  
Shari Kaiser ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Systems Biology ◽  
Multidrug Resistant ◽  
First Century ◽  
Research Paradigm ◽  
Host Interactions ◽  
Disease Research ◽  
The Past ◽  
Infectious Disease Research ◽  
Waterborne Illnesses

ABSTRACT The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm.

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