scholarly journals Intragenic Distribution of IS 6110 in Clinical Mycobacterium tuberculosis Strains: Bioinformatic Evidence for Gene Disruption Leading to Underdiagnosed Antibiotic Resistance

2021 ◽  
Author(s):  
Rudy Antoine ◽  
Cyril Gaudin ◽  
Ruben C. Hartkoorn
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Gene Disruption ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Drug Resistant ◽  
Single Nucleotide ◽  
Drug Resistant Tuberculosis ◽  
Treatment Choices ◽  
Resistant Tuberculosis

To help control the spread of drug-resistant tuberculosis and to guide treatment choices, it is important that rapid and accurate molecular diagnostic tools are used. Current molecular diagnostic tools detect the most common antibiotic-resistance-conferring mutations in the form of single nucleotide changes, small deletions, or insertions.

scholarly journals Use of fluorescein diacetate (FDA) staining to detect viable Mycobacterium tuberculosis

2012 ◽  
Vol 11 (4) ◽  
pp. 322-330 ◽  
Author(s):  
Shamima Islam ◽  
Farjana Rahman ◽  
Saurab Kisore Munshi ◽  
Jewel Ahmed ◽  
S M Mostafa Kamal ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Treatment Failure ◽  
Medical Science ◽  
Multidrug Resistant ◽  
Fluorescein Diacetate ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Auramine O

Objective: Drug resistant tuberculosis has long been a common problem prevailing in developing countries including Bangladesh. Present study focused on the rapid identification of live Mycobacterium tuberculosis among treatment failure cases.Materials and Methods: Sputum samples from a total of 100 category-I and category-II treatment failure cases, assumed as multidrug resistant tuberculosis, were studied through fluorescein diacetate (FDA) staining under light emitting diode (LED) fluorescence microscope. Considering culture method as gold standard, we also compared the results of FDA staining with that of auramine O staining.Results: A total of 85% acid-fast bacilli were detected by FDA staining, 82% by auramine O staining and a total of 85% isolates were detected in Lowenstein-Jensen (LJ) culture. The sensitivity of FDA staining (96.47%) was estimated to be slightly higher than that of auramine O staining (91.76%). Moreover,76.47% cases were detected as multidrug resistant tuberculosis (MDR-TB). Conclusion: Taken together, FDA staining method has been proposed to be appropriate for the rapid diagnosis of drug resistant tuberculosis. DOI: http://dx.doi.org/10.3329/bjms.v11i4.12605 Bangladesh Journal of Medical Science Vol. 11 No. 04 Oct’12

scholarly journals Bazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing Autophagy

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Qi Ouyang ◽  
Kehong Zhang ◽  
Dachuan Lin ◽  
Carl G. Feng ◽  
Yi Cai ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
New Host ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Receptor Modulator ◽  
Resistant Tuberculosis ◽  
Negative Side Effects

ABSTRACT Tuberculosis (TB) is still the leading killer caused by Mycobacterium tuberculosis infection. There is a clear need for new treatment strategy against TB. It has been reported that tamoxifen, known as a selective estrogen receptor modulator (SERM), exhibits antimycobacterial activity and inhibits M. tuberculosis growth in macrophages. However, it remains unknown whether such antimicrobial activity is a general property of all SERMs and how it works. In this study, we identified that bazedoxifene (BZA), a newer SERM, inhibits intracellular M. tuberculosis growth in macrophages. BZA treatment increases autophagosome formation and LC3B-II protein expression in M. tuberculosis-infected macrophages. We further demonstrated that the enhancement of autophagy by BZA is dependent on increased reactive oxygen species (ROS) production and associated with phosphorylation of Akt/mTOR signaling. In summary, our data reveal a previously unappreciated antimicrobial function of BZA and suggest that future investigation focusing on the mechanism of action of SERMs in macrophages may lead to new host-directed therapies against TB. IMPORTANCE Since current strategies for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have low efficacy and highly negative side effects, research on new treatments including novel drugs is essential for curing drug-resistant tuberculosis. Host-directed therapy (HDT) has become a promising idea to modulate host cell responses to enhance protective immunity against pathogens. Bazedoxifene (BZA), which belongs to a new generation of SERMs, shows the ability to inhibit the growth of M. tuberculosis in macrophages and is associated with autophagy. Our findings reveal a previously unrecognized antibacterial function of BZA. We propose that the mechanism of SERMs action in macrophages may provide a new potential measure for host-directed therapies against TB.

scholarly journals Association between embB Codon 306 Mutations and Drug Resistance in Mycobacterium tuberculosis

2007 ◽  
Vol 51 (7) ◽  
pp. 2618-2620 ◽  
Author(s):  
Xin Shen ◽  
Guo-miao Shen ◽  
Jie Wu ◽  
Xiao-hong Gui ◽  
Xia Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Odds Ratio ◽  
Rapid Detection ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Candidate Marker ◽  
Resistant Tuberculosis

ABSTRACT embB306 mutants were detected in both ethambutol (EMB)-resistant and EMB-susceptible strains of Mycobacterium tuberculosis. Multidrug-resistant (MDR) strains had a higher proportion of embB306 mutants than non-MDR strains (odds ratio, 6.78; P < 0.001). The embB306 locus is a candidate marker for rapid detection of MDR and extremely drug resistant tuberculosis.

scholarly journals A Rapid Drug Resistance Genotyping Workflow for Mycobacterium tuberculosis, Using Targeted Isothermal Amplification and Nanopore Sequencing

2021 ◽  
Author(s):  
Harriet D. Gliddon ◽  
Dan Frampton ◽  
Vanisha Munsamy ◽  
Jude Heaney ◽  
Thomas Pataillot-Meakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Nanopore Sequencing ◽  
Drug Resistant ◽  
Resource Limited Settings ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Resource Limited ◽  
Drug Resistance Genotyping ◽  
High Level

Current methods for diagnosing drug-resistant tuberculosis are time consuming, resulting in delays in patients receiving treatment and in transmission onwards. They also require a high level of laboratory infrastructure, which is often only available at centralized facilities, resulting in further delays to diagnosis and additional barriers to deployment in resource-limited settings.

scholarly journals Mutation in an Unannotated Protein Confers Carbapenem Resistance in Mycobacterium tuberculosis

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Pankaj Kumar ◽  
Amit Kaushik ◽  
Drew T. Bell ◽  
Varsha Chauhan ◽  
Fangfang Xia ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genetic Basis ◽  
Carbapenem Resistance ◽  
Drug Resistant ◽  
Binding Affinities ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Recent Developments

ABSTRACT β-Lactams are the most widely used antibacterials. Among β-lactams, carbapenems are considered the last line of defense against recalcitrant infections. As recent developments have prompted consideration of carbapenems for treatment of drug-resistant tuberculosis, it is only a matter of time before Mycobacterium tuberculosis strains resistant to these drugs will emerge. In the present study, we investigated the genetic basis that confers such resistance. To our surprise, instead of mutations in the known β-lactam targets, a single nucleotide polymorphism in the Rv2421c-Rv2422 intergenic region was common among M. tuberculosis mutants selected with meropenem or biapenem. We present data supporting the hypothesis that this locus harbors a previously unidentified gene that encodes a protein. This protein binds to β-lactams, slowly hydrolyzes the chromogenic β-lactam nitrocefin, and is inhibited by select penicillins and carbapenems and the β-lactamase inhibitor clavulanate. The mutation results in a W62R substitution that reduces the protein's nitrocefin-hydrolyzing activity and binding affinities for carbapenems.

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