A5081061481- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Cancer therapeutics and mechanisms
- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Pneumonia and Respiratory Infections
- Pneumocystis jirovecii pneumonia detection and treatment
- Diagnosis and treatment of tuberculosis
- Biochemical and Molecular Research
- Infectious Diseases and Tuberculosis
- Evolution and Genetic Dynamics
- HIV/AIDS drug development and treatment
- Immunodeficiency and Autoimmune Disorders
- Innovative Microfluidic and Catalytic Techniques Innovation
- Infectious Diseases and Mycology
- Cystic Fibrosis Research Advances
- Antimicrobial Resistance in Staphylococcus
- Cytomegalovirus and herpesvirus research
- Bioactive Compounds and Antitumor Agents
- Biosensors and Analytical Detection
- Bacillus and Francisella bacterial research
- Phytochemistry and Bioactivity Studies
- vaccines and immunoinformatics approaches
- ATP Synthase and ATPases Research
- Drug Transport and Resistance Mechanisms
Public Health Agency of Sweden
2015-2024
Swedish Institute
2003-2014
Karolinska Institutet
2006
Thirty-four pyrazinamide-resistant and 37 pyrazinamide-susceptible Mycobacterium tuberculosis complex strains were analyzed for pncA gene mutations. None of the sensitive had any mutations, apart from silent whereas all but one resistant strain showed By using sequencing as a means early resistance detection, inconsistency phenotypic pyrazinamide assays can be circumvented.
Pyrazinamide (PZA) is a prodrug that converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations offers potential for rapid detection pyrazinamide resistance (PZA(r)). However, genetic variants are highly variable and scattered over full length pncA, complicating development molecular test. We performed large multicenter study assessing sequence variations 1,950 clinical isolates, including 1,142...
ScopeSeveral methods are used worldwide for antibiotic susceptibility testing (AST) the Mycobacterium tuberculosis complex (MTBC). The variability in results obtained with these hampers setting epidemiological cut-off (ECOFF) values and clinical breakpoints according to EUCAST guidelines. Methods determination of minimal inhibitory concentrations (MICs) need be standardized MTBC isolates old new agents. Our objective was establish a reference method MIC MTBC.MethodsThe antimycobacterial...
Abstract Objectives To develop a robust phenotypic antimicrobial susceptibility testing (AST) method with correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug. Methods The Becton Dickinson Mycobacterial Growth Indicator Tube™ (MGIT) system was used at six laboratories to determine MICs of phylogenetically diverse collection 356 Mycobacterium tuberculosis complex (MTBC) strains establish epidemiological cut-off value pretomanid. were correlated WGS...
For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distributions of wild-type isolates have not been systematically evaluated despite their importance for establishing antimicrobial susceptibility testing (AST) breakpoints. We gathered MIC drugs used against the Mycobacterium avium complex (MAC) and abscessus (MAB) obtained by commercial broth microdilution (SLOMYCOI RAPMYCOI) from 12 laboratories. Epidemiological cut-off values (ECOFFs) tentative ECOFFs (TECOFFs)...
ObjectivesThe aim of this study was to establish wild-type MIC distributions first-line drugs for Mycobacterium tuberculosis, as well explore the usefulness such when setting clinical breakpoints.
ABSTRACT Tuberculosis patients may harbor both drug-susceptible and -resistant bacteria, i.e., heteroresistance. We used mixtures of rifampin-resistant -susceptible Mycobacterium tuberculosis strains to simulate heteroresistance in patient samples. Molecular tests can be for earlier discovery multidrug resistance (MDR), but the sensitivity detect is unknown. Conventional phenotypic drug susceptibility testing was most sensitive, whereas two line probe assays sequencing were unable clinically...
ABSTRACT The Mycobacterium tuberculosis Beijing genotype has drawn attention because it is often strongly associated with multidrug-resistant (MDR-TB). A possible reason that the strains may have an enhanced capacity to develop drug resistance. In this study, we used Luria-Delbrück fluctuation test investigate whether of and non-Beijing genotypes exhibit differences in acquisition M . reference strain H37Rv 12 fully drug-susceptible clinical isolates, 6 which were genotype, examined. To...
The aim of this study was to clarify the conflicting data regarding cross-resistance and drug-resistance mechanisms for cyclic peptide capreomycin aminoglycosides amikacin kanamycin by comparing genotypes phenotypes clinical isolates in vitro selected mutants Mycobacterium tuberculosis. genes rrs tlyA promoter region eis 152 M. tuberculosis (including 55 resistant) 44 capreomycin-, amikacin- kanamycin-resistant were sequenced. In addition, MICs capreomycin, on Middlebrook 7H10 determined....
ABSTRACT Patients may harbor both drug-susceptible and -resistant bacteria, representing heteroresistance. We studied mixtures of isoniazid-resistant -susceptible Mycobacterium tuberculosis strains. Conventional drug susceptibility testing was the most sensitive method detection, whereas line probe assay sequencing were not able to detect clinically relevant 1% proportion resistant bacteria.
ABSTRACT The antigen 85 (Ag85) protein family, consisting of Ag85A, -B, and -C, is vital for Mycobacterium tuberculosis due to its role in cell envelope biogenesis. mycoloyl transferase activity these proteins generates trehalose dimycolate (TDM), an lipid essential M. virulence, wall arabinogalactan-linked mycolic acids. Inhibition enzymes through substrate analogs hinders growth mycobacteria, but a link acid synthesis has not been established. In this study, we characterized novel...
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 MTB individual drugs, but not considered the and cannot capture latent structure genomic that corresponds lineages.We used large cohort TB patients from 16 countries across six continents where whole-genome sequences for each isolate associated phenotype anti-TB were obtained...
Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains are a serious health problem in India, also contributing to one-fourth of the global MDR (TB) burden. About 36% MTBC reported fluoroquinolone (FQ) resistant leading high pre-extensively drug-resistant (pre-XDR) and XDR-TB (further resistance against bedaquiline and/or linezolid) rates. Still, factors driving MDR/pre-XDR epidemic India not well defined. In retrospective study, we analyzed 1852 consecutive obtained...
Pyrazinamide (PZA) is a potent first-line agent for the treatment of tuberculosis (TB) with activity also against significant part drug-resistant Mycobacterium strains. Since PZA active only at acid pH, testing susceptibility to difficult and insufficiently reproducible. The recommended critical concentration (MIC, 100 mg/liter) used in Bactec systems (460 MGIT 960) has not been critically evaluated wild-type MIC distributions clinical isolates tuberculosis. Using 960 system, we determined...
DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, prevalence pre-existing resistance to FQs likely restrict their clinical value. We describe novel class N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting activity. The mechanism inhibition was distinct from fluoroquinolones, shown ability inhibit growth...
ABSTRACT Pyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDR PZA-S ) tuberculosis (TB). pncA gene mutations are usually detected in clear majority (>90%) PZA-resistant strains but obviously not all. Rapid reliable PZA drug susceptibility testing (DST) critical whenever to be used regimen, least MDR TB. In this study, we selected 26 isolates reported carry wild-type gene. To confirm resistance, was repeated...
The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess deficit amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding parameters, such as dN/dS, but analyzing very large data sets poses major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation and apply it to 3,979 across 10,209 tuberculosis genomes...
The distribution and resistance levels of 189 in vitro-selected rifampin-resistant Mycobacterium tuberculosis mutants Beijing other genotypes were determined. Apart from a higher amount codon 522 point mutations large deletions, spread similar to that reported for clinical isolates was seen. Most correlated with high-level resistance; lower level, or MIC <16 mg/liter, associated mutations. Multiple detected two mutants.
ObjectivesTo describe wild-type distributions of the MIC fluoroquinolones for Mycobacterium tuberculosis in relation to current critical concentrations used drug susceptibility testing and pharmacokinetic/pharmacodynamic (PK/PD) data.
The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring need for accurate reproducible drug susceptibility testing (DST). epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type is an important but rarely used tool indicating breakpoints against Mycobacterium tuberculosis. In this study, we established MIC distributions on Middlebrook 7H10 medium amikacin, kanamycin,...
For an infecting bacterium the human body provides several potential ecological niches with both internally (e.g. host immunity) and externally antibiotic use) imposed growth restrictions that are expected to drive adaptive evolution in bacterium, including development of resistance. To determine extent pattern heterogeneity generated a bacterial population during long-term treatment, we examined monoclonal Mycobacterium tuberculosis infection resistant mutants isolated from one patient...
Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) Mycobacterium against PZA not included World Health Organization's yearly proficiency testing. There an increasing need to establish quality control DST.To evaluate performance DST and introduce assurance system for test Sweden.Panels with PZA-susceptible -resistant isolates were used three rounds all five Swedish clinical TB laboratories our reference...