A5015932171- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Infectious Diseases and Mycology
- Diagnosis and treatment of tuberculosis
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Infectious Diseases and Tuberculosis
- Bacteriophages and microbial interactions
- Bacterial Identification and Susceptibility Testing
- Pharmacological Effects of Natural Compounds
- Enzyme Structure and Function
- Cancer Genomics and Diagnostics
- Heat shock proteins research
- Cytokine Signaling Pathways and Interactions
- ATP Synthase and ATPases Research
- Genomics and Phylogenetic Studies
Sciensano (Belgium)
2019-2023
Institut Scientifique de Santé Publique
2010-2017
Institut Pasteur
2000-2005
Antibiotic resistance is one of the biggest threats to human health globally. Alarmingly, multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis have now spread worldwide. Some key antituberculosis antibiotics are prodrugs, for which mechanisms mainly driven by mutations in bacterial enzymatic pathway required their bioactivation. We developed drug-like molecules that activate a cryptic alternative bioactivation ethionamide M. tuberculosis, circumventing classic...
ABSTRACT Species identification and drug susceptibility testing (DST) of mycobacteria are important yet complex processes traditionally reserved for reference laboratories. Recent technical improvements in matrix-assisted laser desorption ionization–time flight mass spectrometry (MALDI-TOF MS) has started to facilitate routine mycobacterial identifications clinical In this paper, we investigate the possibility performing phenotypic MALDI-based DST mycobacteriology using recently described...
Accumulating evidence suggests that the bactericidal activity of some antibiotics may not be directly initiated by target inhibition. The isoniazid (INH), a key first-line antituberculosis drug currently known to inhibit mycolic acid synthesis, becomes extremely poor under stress conditions, such as hypoxia and starvation. This inhibition fully explain drug. Here, we report INH rapidly increased Mycobacterium bovis BCG cellular ATP levels enhanced oxygen consumption. INH-triggered increase...
Mycobacterium tuberculosis is wrapped in complex waxes, impermeable to most antibiotics. Comparing bovis BCG and M. mutants that lack phthiocerol dimycocerosates (PDIM) and/or phenolic glycolipids with wild-type strains, we observed glycopeptides strongly inhibited PDIM-deprived mycobacteria. Vancomycin together a drug targeting lipid synthesis multidrug-resistant (MDR) extensively drug-resistant (XDR) clinical isolates. Our study puts the pipeline of potential antituberculosis (TB) agents...
The Xpert® MTB/RIF assay detects the presence of Mycobacterium tuberculosis and its resistance to rifampicin (RMP) directly in sputum samples. Discrepant results were observed a case smear-positive pulmonary that was Xpert-resistant but phenotypically susceptible RMP. Complementary investigations (repeat Xpert, Genotype®MTBDRplus sequencing rpoB gene) revealed silent mutation gene, leading conclusion false-positive Xpert result. As misinterpretation may lead inappropriate treatment,...
The sensitivity of Mycobacterium tuberculosis , the pathogen that causes (TB), to antibiotic prodrugs is dependent on efficacy activation process transforms into their active antibacterial moieties. Various oxidases M. have potential activate prodrug ethionamide. Here, we used medicinal chemistry coupled with a phenotypic assay select N-acylated 4-phenylpiperidine compound series. lead compound, SMARt751, interacted transcriptional regulator VirS which regulates mymA operon encoding...
The use of whole-genome sequencing (WGS) for routine typing bacterial isolates has increased substantially in recent years. For Mycobacterium tuberculosis (MTB), particular, WGS the benefit drastically reducing time required to generate results compared most conventional phenotypic methods. Consequently, a multitude solutions analyzing MTB data have been developed, but their successful integration clinical and national reference laboratories is hindered by requirement validation, which...
The tuberculosis (TB) incidence rate in Brussels-Capital Region is 3-fold higher than Belgium as a whole. Eight years after the realization of initial prospective population-based molecular epidemiology investigations this Region, similar study over period 2010-2013 was conducted. TB strains isolated from 945 patients were submitted to genotyping by standardized 24-locus-MIRU-VNTR typing and spoligotyping. phylogenetic analysis showed that LAM (16.7%) Haarlem (15.7%) branches are two most...
Pathogenic mycobacteria possess two homologous chaperones encoded by cpn60.1 and cpn60.2. Cpn60.2 is essential for survival, providing the basic chaperone function, while Cpn60.1 not. In present study, we show that inactivation of Mycobacterium bovis BCG (Mb3451c) gene does not significantly affect bacterial growth in 7H9 broth, but this knockout mutant (Δcpn60.1) forms smaller colonies on solid 7H11 medium than parental complemented strains. When growing Sauton medium, Δcpn60.1 exhibits a...
Mycobacterium avium represents a health concern for both humans and pigs. The characterisation of its subspecies is an important step improving the understanding epidemiology control this pathogen. Ninety-two human M. strains were selected retrospective study. Subspecies determination by rpoB sequencing IS 1245 /IS 901 analysis showed that 98.9% Belgian belong to hominissuis (MAH). Some these MAH present particular profiles (absence false IS901 detection provoked presence Mav6 ). In...
Mycobacterium chimaera arouses an increasing public health concern, as this non-tuberculous mycobacterium (NTM) has recently been associated with life-threatening cardiac infections. M. and Mycobacteriumintracellulare are genetically very close but appeared to present different epidemiological clinical significance. Therefore, it become important for laboratories use adequate techniques allowing precise species identification. To date, most commercially available laboratory assays cannot...
PknD is one of the eleven eukaryotic-like serine/threonine protein kinases (STPKs) Mycobacterium tuberculosis (Mtb). In vitro phosphorylation assays with active recombinant showed that intracellular NAD+-dependent malate dehydrogenase (MDH) a substrate this kinase. MDH, an energy-supplying enzyme, catalyzes interconversion and oxaloacetate plays crucial roles in several metabolic pathways including citric acid cycle. The site was identified on threonine residues inhibited MDH activity....
Since January 2019, the Belgian National Reference Center for Mycobacteria (NRC) has switched from conventional typing to prospective whole-genome sequencing (WGS) of all submitted Mycobacterium tuberculosis complex (MTB) isolates. The ISO17025 validated procedure starts with semi-automated extraction and purification gDNA directly MGIT tubes, without preceding subculturing. All samples are then sequenced on an Illumina MiSeq sequencer analyzed using in-house developed bioinformatics...
Here, we report the development and key features of first external quality assessment (EQA) scheme for Mycobacterium tuberculosis whole-genome sequencing (WGS). The results four rounds (2017 to 2020) implementation within European reference laboratories network (ERLTB-Net-2) are presented discussed. EQA panels comprising 10 genomic DNAs were distributed ERLTB-Net 2 volunteering participate in this exercise. Since 2018, five FASTQ files added better assess dry WGS processes, 2020, three...
Heat-shock proteins (Hsps) from various origins are known to share a conserved structure and assumed be key partners in the biogenesis of proteins. Fractionation mycobacterial Hsp60, 65 kDa protein also called Cpn60, Mycobacterium bovis BCG zinc-deficient culture filtrate on phenyl-Sepharose followed by Western blotting revealed existence four Hsp60-1 Hsp60-2 forms, based their hydrophobicity behaviour. species were further purified ion-exchange chromatography partial amino acid sequences...
The gene encoding of an alcohol dehydrogenase C (ADHC) from Mycobacterium smegmatis was cloned and sequenced. protein encoded by this has 78% identity with tuberculosis bovis BCG ADHC. M. ADHC purified the kinetic parameters enzyme showed that using NADPH as electron donor it a strong preference for aliphatic aromatic aldehyde substrates. Like ADHC, is more likely to act reductase than dehydrogenase. discovery such in fast-growing, easily engineered mycobacterial species opens way...
Introduction In 2007, a new federal legislation in Belgium prohibited non-biosafety level 3 laboratories to process culture tubes suspected of containing mycobacteria. Aim To present mycobacterial surveillance/diagnosis data from the Belgian National Reference Centre for mycobacteria (NRC) 2007 2016. Methods This retrospective observational study investigated numbers analyses at NRC and false positive cultures (interpreted as referring clinical laboratories, but with no DNA detected by PCR...
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a public health issue, particularly due to multi-drug-resistant Mtb. The bacillus is wrapped in waxy envelope containing lipids acting as essential virulence factors, accounting for the natural antibiotic resistance of mycobacteria. Telacebec (previously known Q203) promising new anti-TB agent inhibiting cytochrome bc1 complex mycobacterial electron transport chain (ETC). Here, we show that telacebec-challenged M. bovis...
Mycobacterium avium is one of the most frequently isolated nontuberculous mycobacteria, responsible human and porcine infections.The species M consists four subspecies; subspecies (MAA), silvaticum (MAS), paratuberculosis (MAP) hominissuis (MAH) (Thorel others 1990, Mijs 2002, Turenne 2007).Given its pathogenicity for both beings pigs, MAH represents an increasing public health concern (Pate 2011, Iwamoto 2012, Muwonge 2014).In these mycobacteria provoke granulomatous lesions mainly in lymph...