A5055089481- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Infectious Diseases and Tuberculosis
- Bacterial biofilms and quorum sensing
- Diagnosis and treatment of tuberculosis
- Antibiotics Pharmacokinetics and Efficacy
- Cancer therapeutics and mechanisms
- Enzyme Structure and Function
- Pneumocystis jirovecii pneumonia detection and treatment
- Pneumonia and Respiratory Infections
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Infectious Diseases and Mycology
- Bacterial Identification and Susceptibility Testing
- Antimicrobial Resistance in Staphylococcus
- Plant Pathogenic Bacteria Studies
- Microbial Natural Products and Biosynthesis
- Infections and bacterial resistance
- Antibiotic Use and Resistance
- Biochemical and Molecular Research
- Pharmaceutical and Antibiotic Environmental Impacts
- Enzyme Production and Characterization
- Infective Endocarditis Diagnosis and Management
- RNA and protein synthesis mechanisms
Sorbonne Université
2013-2022
Assistance Publique – Hôpitaux de Paris
2013-2022
Centre d'Immunologie et des Maladies Infectieuses
2014-2022
Inserm
2010-2022
Pitié-Salpêtrière Hospital
2012-2022
CNR de la Résistance aux Antibiotiques
2005-2021
Centre National de la Recherche Scientifique
1988-2019
Université Paris Cité
1988-2018
Hôpital Charles-Foix
2016-2018
Laboratoire National de Référence
2002-2018
ABSTRACT The GenoType MTBDR sl test rapidly detects resistance to ethambutol, fluoroquinolones, and second-line aminoglycosides (amikacin kanamycin) cyclic peptide (capreomycin) in Mycobacterium tuberculosis . A set of 41 multidrug-resistant (MDR) M. strains, 8 extensively drug-resistant (XDR) 3 non-MDR strains were tested by the DNA sequencing resistance-determining regions gyrA gyrB (fluoroquinolones [FQ]), rpsL (streptomycin), rrs tlyA (aminoglycosides and/or peptide), embB (ethambutol)....
Serratia marcescens S6 produces a pI 9.7 carbapenem-hydrolyzing beta-lactamase that is probably encoded by the chromosome (Y. Yang, P. Wu, and D. M. Livermore, Antimicrob. Agents Chemother. 34:755-758, 1990). A total of 11.3 kb genomic DNA from this strain was cloned into plasmid pACYC184 in Escherichia coli. After further subclonings, gene (blaSme-1) sequenced (EMBL accession number Z28968). The corresponded to an 882-bp open reading frame which 294-amino-acid polypeptide. This preceded -10...
Infections due to strains of Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii resistant third-generation cephalosporins have been observed recently in France the Federal Republic Germany. This resistance phenotype is production new plasmid-mediated, broad-substrate-range β-lactamases designated TEM-3 TEM7. DNA-DNA hybridization analysis with a probe specific for TEM-1 indicated that corresponding genes blaT-3 blaT-7 were variants structural TEM-type β-lactamases. In present...
Pyrazinamidase (PncA) activates the first-line antituberculous drug pyrazinamide into pyrazinoic acid. The crystal structure of Mycobacterium tuberculosis PncA protein has been determined, showing significant differences in substrate binding cavity when compared to pyrazinamidases from Pyrococcus horikoshii and Acinetobacter baumanii. In M. tuberculosis, this region was found hold a Fe(2+) ion coordinated by one aspartate three histidines, them corresponding His57 which is replaced Asp...
The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak multidrug-resistant patients from Horn Africa and Sudan.On April 29 May 30, 2016, Swiss German National Mycobacterial Reference Laboratories independently triggered investigation after four were diagnosed with tuberculosis. In this molecular epidemiological study, we prospectively defined cases 24-locus mycobacterial interspersed...
ABSTRACT TMC207 is a new antituberculous drug belonging to the diarylquinoline class which very efficiently inhibits ATP synthase of mycobacteria such as Mycobacterium tuberculosis , one most important pathogens in world. In order map amino acid residues involved binding drug, we have selected vitro TMC207-resistant mutants from M. and diverse atypical mycobacteria. Six distinct mutations, Asp28→Gly, Asp28→Ala, Leu59→Val, Glu61→Asp, Ala63→Pro, Ile66→Met, been identified subunit c forming C...
The atpE gene encoding the subunit c of ATP synthase Mycobacterium tuberculosis, target new diarylquinoline drug R207910, has been sequenced from in vitro mutants resistant to drug. previously reported mutation A63P and a mutation, I66M, were found. genetic diversity 13 mycobacterial species was also investigated, revealing that region involved resistance R207910 is conserved, except xenopi which highly conserved residue Ala63 replaced by Met, modification may be associated with natural M. R207910.
We assessed the performance of Genotype MTBDR line probe assay that offers simultaneous identification Mycobacterium tuberculosis and its resistance to rifampin (RIF) isoniazid (INH) by detecting most commonly found mutations in rpoB katG genes. One hundred thirteen M. isolates were tested. The nucleotide sequences inhA genes mabA-inhA promoter region also determined. detected 100% 67% (n = 64) strains resistant RIF INH, respectively. Among latter, 62 carried a Ser315Thr mutation katG, 59...
The nucleotide sequence of the tetracycline resistance gene encoded by self-transferable plasmid pIP1433 in Campylobacter coli BM2509 has been determined. gene, tetO, was located an open reading frame 1917 bp corresponding to a protein with calculated Mr 72 290. transcriptional and translational signals have identified. tetO exhibits 76% identity tetM from Streptococcus deduced amino acid sequences are 77% homologous. substitutions scattered throughout indicating that two genes diverged...
Two clinical strains of Escherichia coli (2138) and Enterobacter cloacae (7506) isolated from the same patient in France showing resistance to extended-spectrum cephalosporins low susceptibility imipenem were investigated. Both harbored plasmid-contained bla(TEM-1) bla(KPC-2) genes. bla(KLUC-2), encoding a mutant chromosomal beta-lactamase Kluyvera cryocrescens, was also identified at plasmid location E. 7506, suggesting ISEcp1-assisted escape bla(KLUC) chromosome. Determination KPC-2...
The low-affinity penicillin-binding protein (PBP) 5 is the main β-lactam target and responsible for resistance to this class of antibiotics in Enterococcus faecium. PBP variants 15 clinical isolates (including 8 resistant vancomycin) with different levels were analyzed. Most highly β-lactam-resistant produced small quantities low affinity. This was associated particular amino acid substitutions: an Ala or Ile Thr-499, a Glu Val-629, Pro Ser-667. A change Met-485 Thr (adjacent conserved SDN...
A new set of mutations, including transposition the insertion sequence IS6110, was identified in pncA gene from 19 pyrazinamide-resistant Mycobacterium tuberculosis strains. Alignment PncA protein M. with homologous proteins different bacterial species revealed three highly conserved regions which may play an important role processing pyrazinamide.
ABSTRACT Ethionamide (ETH) needs to be activated by the mono-oxygenase EthA, which is regulated EthR, in order active against Mycobacterium tuberculosis . The drug targets enzyme InhA, involved cell wall biosynthesis. Resistance ETH has been reported result from various mechanisms, including mutations altering EthA/EthR, InhA and its promoter, NADH dehydrogenase encoded ndh , MshA enzyme, mycothiol We searched for such 87 clinical isolates: 47 ETH-resistant (ETH r ) isolates, 24...
The MmpS family (mycobacterial membrane protein small) includes over 100 small proteins specific to the genus Mycobacterium that have not yet been studied experimentally. genes encoding are often associated with mmpL genes, which homologous RND (resistance nodulation cell division) of Gram-negative bacteria encode functioning as multidrug efflux system. We showed by molecular genetics and biochemical analysis MmpS4 in smegmatis is required for production export large amounts surface...
ABSTRACT Modification of codon 306 in embB is regarded as the main mechanism leading to ethambutol (ETB) resistance clinical isolates Mycobacterium tuberculosis . However, numerous mutations elsewhere embCAB locus and embR , a putative transcriptional activator this locus, have been reported be involved ETB resistance. Here, we investigated diversity nucleotide variations observed M. complex from France. These regions were sequenced 71 ETB-resistant (ETB-R) 60 ETB-susceptible (ETB-S) known...
Non-tuberculous mycobacteria (NTM) are emerging pathogens causing difficult-to-treat infections. We tested a new assay (GenoType NTM-DR) that detects natural and acquired resistance mechanisms to macrolides aminoglycosides in frequently isolated NTM species.Performance was assessed on 102 isolates including reference strains [16 Mycobacterium avium , 10 intracellulare 8 chimaera 15 chelonae 53 abscessus (including subsp. isolates, 18 with t28 erm(41) c28, 13 bolletii 12 massiliense...
Mycobacterium africanum consists of Lineages L5 and L6 the tuberculosis complex (MTBC) causes human in specific regions Western Africa, but is generally not transmitted other parts world. Since M. evolutionarily closely placed between globally dispersed animal-adapted MTBC-members, these lineages provide valuable insight into evolution. Here, we have collected 15 strains isolated France over 4 decades. Illumina sequencing phylogenomic analysis revealed a previously underappreciated diversity...
Multidrug resistant (MDR) strains of Mycobacterium tuberculosis represent an obstacle to eradicating (TB) due the low treatment success rate MDR TB. Among them, B0/W148 clone has recently evolved from M. Beijing lineage 2 and widely disseminated in Russia Europe. To get more insights into genetic factors underlying evolutionary addition environmental patient-related features, we focused on two mutations specific this that are found transcriptional regulators WhiB6 KdpDE investigated a H37Rv...
A strain of Mycobacterium tuberculosis resistant to ofloxacin was selected in a patient with long history multidrug-resistant eventually treated by combined other second-line drugs. mutation the gyrA gene hypothesized bethe mechanism acquired resistance this strain. Chromosomal DNA strains MTBl, isolated before treatment and susceptible (MIC, 1 µg /mL), MTB2, during 32 /mL),was amplified polymerase chain reaction (PCR) using two oligonucleotide primers highly homologous sequences flanking...
Molecular detection of rifampin resistance (rpoB analysis) in Mycobacterium leprae was determined for 49 patients who experienced relapse multibacillary leprosy and 34 untreated patients. ofloxacin (gyrA the 12 had received ofloxacin. Results molecular tests were compared with reference susceptibility test mouse footpad. Overall, efficiency detection—that is, positive DNA amplification—was 95%, whereas that vivo 55% (P > .001). fully concordant when both available—that 35 rifampin-sensitive...
We have determined the nucleotide sequence of blaT-3 gene plasmid pCF04 which confers resistance to penicillins and most cephalosporins by mediating production TEM-3 β-lactamase. The deduced amino acid differed in two positions from that TEM-2 penicillinase: Lys (TEM-3) for Glu (TEM-2) at position 102, Ser Gly 236 unprocessed protein. Examination location modified acids tertiary structure class A β-lactamases suggested they both are part substrate binding site. Analysis, vitro recombination,...