Sara Plesnik

Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

Ivan Barilar, Simone Battaglia, Emanuele Borroni, Angela Pires Brandão et autres

The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, …

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Two-stage tuberculosis diagnostics: combining centrifugal microfluidics to detect TB infection and Inh and Rif resistance at the point of care with subsequent antibiotic resistance profiling by targeted NGS

Judith Schlanderer, Harald Hoffmann, Jan Lüddecke, Andrey Golubov et autres

, a diagnostic sensitivity of 96%, and a diagnostic specificity of 100% for MTBC detection. Coupled tNGS successfully provided resistance profiles, demonstrated for samples from 17 patients. To the best of our knowledge, the presented combination of PoC qPCR with tNGS allows …

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Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Lindsay Sonnenkalb, Joshua James Carter, Andrea Spitaleri, Zamin Iqbal et autres

BACKGROUND: Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we …

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High fluoroquinolone resistance proportions among multidrug-resistant tuberculosis driven by dominant L2 Mycobacterium tuberculosis clones in the Mumbai Metropolitan Region

Viola Dreyer, Ayan Mandal, Prachi Dev, Matthias Merker et autres

BACKGROUND: Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains are a serious health problem in India, also contributing to one-fourth of the global MDR tuberculosis (TB) burden. About 36% of the MDR MTBC strains are reported fluoroquinolone (FQ) resistant leading to high pre-extensively …

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Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

Iris Finci, Audrey Albertini, Matthias Merker, Sönke Andres et autres

BACKGROUND: Whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex has become an important tool in diagnosis and management of drug-resistant tuberculosis. However, data correlating resistance genotype with quantitative phenotypic antimicrobial susceptibility testing (AST) are scarce. METHODS: In a prospective multicentre observational study, 900 …

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The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis

Paolo Miotto, Claudio Umberto Köser, Philip William Fowler, Zamin Iqbal et autres

Background Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC).We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug …

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Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis

Philip William Fowler, Ivan Barilar, Simone Battaglia, Emanuele Borroni et autres

Abstract Drug susceptibility testing of M. tuberculosis is rooted in a binary susceptible/resistant paradigm. Whilst there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate it is n ecessary to measure the epidemiological …

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Rapid Tuberculosis Diagnostics Including Molecular First- and Second-Line Resistance Testing Based on a Novel Microfluidic DNA Extraction Cartridge

Markus Beutler, Ana R. Homann, Marina Mihalic, Sara Plesnik et autres

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Clinical Evaluation of BD MAX MDR-TB Assay for Direct Detection of Mycobacterium tuberculosis Complex and Resistance Markers

Sabine Hofmann-Thiel, Sara Plesnik, Marina Mihalic, Marion Heiß-Neumann et autres

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GenomegaMap: Within-Species Genome-Wide dN/dS Estimation from over 10,000 Genomes

Daniel J. Wilson, Derrick W. Crook, Tim Peto, A Sarah Walker et autres

The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large …

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A pre-clinical validation plan to evaluate analytical sensitivities of molecular diagnostics such as BD MAX MDR-TB, Xpert MTB/Rif Ultra and FluoroType MTB

Markus Beutler, Sara Plesnik, Marina Mihalic, Laura Olbrich et autres

Rapid diagnosis of tuberculosis (TB) and antibiotic resistances are imperative to initiate effective treatment and to stop transmission of the disease. A new generation of more sensitive, automated molecular TB diagnostic tests has been recently launched giving microbiologists more choice between several …

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DeepAMR for predicting co-occurrent resistance of Mycobacterium tuberculosis

Yang Yang, A Sarah Walker, Daniel J. Wilson, Tim Peto et autres

MOTIVATION: Resistance co-occurrence within first-line anti-tuberculosis (TB) drugs is a common phenomenon. Existing methods based on genetic data analysis of Mycobacterium tuberculosis (MTB) have been able to predict resistance of MTB to individual drugs, but have not considered the resistance co-occurrence and …

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