scholarly journals Drug Resistance Mechanisms in Mycobacterium tuberculosis

Antibiotics ◽  
2014 ◽  
Vol 3 (3) ◽  
pp. 317-340 ◽  
Author(s):  
Juan Palomino ◽  
Anandi Martin
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Resistance Mechanisms

Deregulation of Genes Associated with Alternate Drug Resistance Mechanisms in Mycobacterium tuberculosis

2017 ◽  
Vol 75 (4) ◽  
pp. 394-400 ◽  
Author(s):  
Kalpana Sriraman ◽  
Kayzad Nilgiriwala ◽  
Dhananjaya Saranath ◽  
Anirvan Chatterjee ◽  
Nerges Mistry
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Resistance Mechanisms

scholarly journals Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains

2018 ◽  
Vol 8 ◽  
Author(s):  
H. M. Adnan Hameed ◽  
Md Mahmudul Islam ◽  
Chiranjibi Chhotaray ◽  
Changwei Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Molecular Targets ◽  
Resistance Mechanisms ◽  
Related Drug

scholarly journals Intracellular Drug Targets In Mycobacterium Tuberculosis Revealed By A Chemo-Genetic Approach

2021 ◽  
Author(s):  
Clement K.M. Tsui ◽  
Flavia Sorrentino ◽  
Narula Gagandeep ◽  
Alfonso Mendoza Losanna ◽  
Ruben Gonzalez Rio ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Resistance Mechanisms ◽  
Sequencing Analysis ◽  
Chronic Lung Diseases ◽  
Candidate Drug ◽  
A Genome ◽  
Novel Drug

Abstract Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is one of the most devastating infectious agents in the world. It causes chronic lung diseases to one third of the world’s population. Chemo-genetic characterization through in vitro evolution combined with whole genome sequencing analysis can identify novel drug targets and drug resistance genes in Mtb. We performed a genome analysis of 53 Mtb mutants resistant to 15 different hit compounds. We found nonsynonymous mutations/indels in 30 genes that may be associated with drug resistance acquisitions. Beyond confirming previously identified drug resistance mechanisms such as rpoB and lead targets reported in novel anti-tuberculosis drug screenings such as mmpL3, ethA, mbtA, we discovered several unrecognized candidate drug targets including prrB and TB18.5. The exploration of the M. tuberculosis chemical mutant genomes could help novel drug discovery and structural biology of compounds and asscoiated mechanisms of action relevant to tuberculosis treatment.

Genotypic analysis of multidrug-resistant Mycobacterium tuberculosis isolates from Monterrey, Mexico

2004 ◽  
Vol 53 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Srinivas V. Ramaswamy ◽  
Shu-Jun Dou ◽  
Adrian Rendon ◽  
Zhenhua Yang ◽  
M. Donald Cave ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Secondary Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Genotypic Analysis ◽  
Mdr Tb

Thirty-seven multidrug-resistant and 13 pan-susceptible isolates of Mycobacterium tuberculosis were analysed for the diversity of genotypes associated with known drug-resistance mechanisms. The isolates were obtained from patients attending a university tuberculosis clinic in Monterrey, Mexico. A total of 25 IS6110-RFLP patterns were obtained from the multidrug-resistant tuberculosis (MDR-TB) isolates. Approximately 65 % of the MDR-TB isolates were attributed to secondary resistance. Different drug-susceptibility patterns were seen with the clustered isolates. The percentage of isolates resistant to isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STR) was 100, 97.3, 48.7 and 67.6, respectively. The most common resistance-associated polymorphisms for the four drugs were as follows: INH, Ser315Thr (67.6 %) in katG; RIF, Ser450Leu (41.7 %) in rpoB; EMB, Met306Ile/Val/Leu (66.7 %) in embB; and STR, Lys43Arg (24 %) in rpsL. Drug-resistance-associated mutations were similar to changes occurring in isolates from other areas of the world, but unique, previously unreported, mutations in katG (n = 5), rpoB (n = 1) and rrs (n = 3) were also identified.

scholarly journals Programmable Base Editing in Mycobacterium tuberculosis Using an Engineered CRISPR RNA-Guided Cytidine Deaminase

2021 ◽  
Vol 3 ◽  
Author(s):  
Xin-Yuan Ding ◽  
Si-Shang Li ◽  
Yi-Man Geng ◽  
Mei-Yi Yan ◽  
Guo-Bao Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Molecular Mechanisms ◽  
Cytidine Deaminase ◽  
Point Mutations ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Bacterial Physiology ◽  
Base Editing

Multidrug-resistant Mycobacterium tuberculosis (Mtb) infection seriously endangers global human health, creating an urgent need for new treatment strategies. Efficient genome editing tools can facilitate identification of key genes and pathways involved in bacterial physiology, pathogenesis, and drug resistance mechanisms, and thus contribute to the development of novel treatments for drug-resistant tuberculosis. Here, we report a two-plasmid system, MtbCBE, used to inactivate genes and introduce point mutations in Mtb. In this system, the assistant plasmid pRecX-NucSE107A expresses RecX and NucSE107A to repress RecA-dependent and NucS-dependent DNA repair systems, and the base editor plasmid pCBE expresses a fusion protein combining cytidine deaminase APOBEC1, Cas9 nickase (nCas9), and uracil DNA glycosylase inhibitor (UGI). Together, the two plasmids enabled efficient G:C to A:T base pair conversion at desired sites in the Mtb genome. The successful development of a base editing system will facilitate elucidation of the molecular mechanisms underlying Mtb pathogenesis and drug resistance and provide critical inspiration for the development of base editing tools in other microbes.

Sign in / Sign up

Export Citation Format

Share Document