Patrice Courvalin

..The data provided are mainly, if not exclusively, taken from the work carried out in the laboratory, although there are numerous other examples in the literature...

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..Importantly, it has been recently acquired by Staphylococcus aureus. We shall review the genetics which accounts for this successful dissemination and discuss the possible origins of the resistance genes...

..The 2 phenomena are not mutually exclusive and can be associated in the emergence and more efficient spread of resistance. This review discusses the predictable future of the relationship between antimicrobial drugs and bacteria...

..The diversity, regulation, evolution, and recent dissemination of methicillin-resistant Staphylococcus aureus are then discussed...

..This article reviews the experiments to be performed and the criteria for assessment of safety of antibiotic resistant probiotics...

..In this review, we will consider the predictable future of the relationship between bacteria and antibiotics...

..In this review, the pharmacokinetic-pharmacodynamic (PK-PD) parameters that are intended to lower resistance dissemination are considered exclusively...

..Sequence determination of the flanking regions of the vanG cluster in donor and transconjugants revealed the same 4 bp direct repeats and 22 bp imperfect inverted repeats that delineated the large element...

..The transporter conferred resistance to the hydrophilic quinolones norfloxacin and ciprofloxacin...

..Teicoplanin-resistant mutants were detected as fluorescent bacteria in rabbits treated with teicoplanin. Thus, the reporter system monitored expression of a glycopeptide-resistance gene in vivo at a single-cell level...

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..Vancomycin, but not teicoplanin, was an inducer, which explains teicoplanin susceptibility of VanB-type enterococci...

..These observations indicate that cell wall inhibitors of the beta-lactam and glycopeptide classes exert strong and mutual antagonistic effects on resistance to each other against VanA-type methicillin-resistant S. aureus...

..aureus PA-VRSA is thus likely due to instability of the genetic element, plasmid or transposon, carrying the vanA operon associated with a longer lag phase before growth resumes after induction by vancomycin...

..Ddl drug targeting could therefore be an effective strategy against vancomycin-resistant S. aureus...

..Synthesis of peptidoglycan precursors ending in d-Ala-d-lactate was responsible for oxacillin susceptibility of VRSA-11A and VRSA-11B despite the presence of a wild-type mecA gene in both strains...

..Transcription analysis of the vanE operons suggested that the five genes were cotranscribed from an initiation site located 25 bp upstream from the ATG start codon of vanE...

..The vanE, vanXYE, and vanTE genes conferred inducible low-level resistance to vancomycin after cloning in E. faecalis JH2-2, probably following cross talk with a two-component regulatory system of the host...

..We suggest that the heptanucleotide direct repeat in vanSB may favour the appearance of high level constitutively expressed vancomycin resistance through a 'slippage' type of genetic rearrangement in VanB-type strains...

..The chemical structure of these molecules suggests that amphiphilic compounds are the preferred substrates. The AdeABC and AdeIJK efflux systems contributed in a more than additive fashion to tigecycline resistance...

..Since peptidoglycan precursors ending in D-Ala-D-Lac are not processed by PBP 2', the strain was fully susceptible to oxacillin, despite the production of a wild-type PBP 2'...

..However, since expression of the resistance genes is constitutive, growth of E. faecium BM4339 was not dependent on the presence of glycopeptides in the culture medium...

..16 microM) and exhibited low susceptibility to NaCl (IC50 of >2 M). OXA-63 is the first DBL described for the anaerobic spirochete B. pilosicoli...

..Instead, a mutation in the transcription terminator of the regulatory genes resulted in transcriptional readthrough of the resistance genes from the P(RB) promoter in the absence of vancomycin...

..Altogether, the results are compatible with the notion that van operons in soil Paenibacillus strains and in enterococci have evolved from a common ancestor...

..Our findings are in agreement with the observation that regulation of expression is common in horizontally acquired resistance and represents an efficient evolutionary pathway for resistance determinants to become selectively neutral...

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..Taken together, these data suggest that alteration of DNA supercoiling following a mutation in GyrB was responsible for lack of expression of the vanE operon and thus for vancomycin susceptibility in BM4405-1...

..It therefore appears that posttranscriptional modification of 16S rRNA can confer high-level broad-range resistance to aminoglycosides in gram-negative human pathogens...

..5 microM). The bla(CAD-1) gene is likely to have been acquired by BM4489 and BM4490 as part of a mobile genetic element, since it was not found in the susceptible type strain CIP 101029 and was adjacent to a gene for a resolvase...

..The structural gene was part of a class 1 integron borne by self-transferable plasmid pIP847. GES-type beta-lactamases have not been reported previously in A. baumannii...

..These results suggest that detection of VanD type resistance is of major importance because it abolishes in vivo glycopeptide activity and allows the emergence of mutants highly resistant to glycopeptides...

..which grouped into two phylotypes and all carrying the bla(RAHN) gene. Thus, both organic and conventional fruits and vegetables may constitute significant sources of resistant bacteria and of resistance genes...

..Based on sequence differences, the vanD gene clusters could be assigned to two subtypes: vanD-1 and vanD-4...

..This activity is not required for glycopeptide resistance in BM4339, since this strain cannot synthesize D-alanyl-D-alanine...

..The adeN gene was detected in all of the 30 A. baumannii strains tested and in Acinetobacter calcoaceticus, Acinetobacter nosocomialis, and Acinetobacter pittii...

..This specific and sensitive technique allows detection of glycopeptide-resistant strains, in particular methicillin-resistant S. aureus, that may escape phenotype-based automated rapid methods...

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..These mutations led to constitutive expression of the pump and, thus, to antibiotic resistance. These data indicate that the AdeABC pump is cryptic in wild A. baumannii due to stringent control by the AdeRS two-component system...

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..After induction of VmR, En. faecalis V583 synthesized the cell wall precursor, UDP-N-acetylmuramyl-tetrapeptide-D-lactate, indicating that the mechanism of glycopeptide resistance in strains with the VanA and VanB phenotype is similar...

..This genomic environment suggests a role in the catabolism of a specific sugar for AAC(6')-Iy in Salmonella...

..The products of two upstream open reading frames encoding a putative two-component regulatory system might be involved in the regulation of expression of the adeABC gene cluster...

..The microarray is potentially useful for detection of resistance in A. baumannii and should allow detection of new efflux systems associated with antibiotic resistance...

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..The association of multiple molecular and environmental factors has been implicated in the regional emergence of VRSA in Michigan...

..faecalis V583. The DNA fragment hybridized to VmR strains of En. faecium and En. faecalis, but not to their susceptible derivatives...

..These data strongly suggest that ParC is the primary target for fluoroquinolones in S. pneumoniae and that BM4205-R3 is resistant to higher levels of the drugs following the acquisition of two mutations, including one in gyrA...

..The deduced RmtF protein had 25 to 46% identity with members of the N7 G1405 family of aminoglycoside resistance 16S rRNA methyltransferases...

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..Acquisition of Tn6061 and chromosomal inversions are further examples of intricate mechanisms that contribute to the genome plasticity of P. aeruginosa...

..We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information...

..Molecular typing of the strains with a similar resistance phenotype to broad-spectrum cephalosporins indicated polyclonal spread. ISEcp1 was presumably responsible for dissemination of the bla(CTX-M-like) gene...

..The presence of an integron can account for the various assortments of aminoglycoside resistance genes found associated with blaTEM-3...

..Transglycosylase inhibition was probably the stimulus for the heterologous kinase, as moenomycin was also an inducer...

..The mph(C) gene, as reported for mph(B), also conferred resistance to spiramycin. The mph(A) gene was unique in conferring resistance to azithromycin. The four investigated genes conferred resistance to telithromycin...

..This new insertion belonged to the IS605 family and was composed of two open reading frames encoding putative transposases of two unrelated insertion sequence elements, IS200 and IS1341...

..These observations should incite to exert caution when interpreting data on the DNA transfer from bacteria to mammallian cells when the genes of interest are under the control of the PCMV or PRSV promoter...

..Mutations in adeL were found in the three adeFGH-overexpressing mutants, suggesting that they were responsible for overexpression of AdeFGH...

..Thus, the potential for the dissemination of VRSA clinical isolates should not be underestimated...

..1, c = 177.2 A, and contained two molecules in the asymmetric unit. A complete data set has been collected to 2.35 A resolution from a single crystal under cryogenic conditions using synchrotron radiation...

..The element appeared to be widespread and was detected in strains producing TEM-6 or other TEM variants...

..Resistance was due to production of a new TEM-type beta-lactamase, designated TEM-103/IRT-28, characterized by the Arg(275)Leu substitution and encoded by the ca. 62-kb pIP845 conjugative plasmid of the IncI1 incompatibility group...

..aeruginosa tested and was plasmid borne in the remaining strain. The ant(4')-IIb gene was detected by PCR in some clinical strains of P. aeruginosa from the same hospital but not in members of other bacterial genera...

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..In conclusion, the use of a high dose of vancomycin was necessary for the treatment of experimental enterococcal endocarditis due to VanE-type strains...

..Linkage between the vanB2 gene cluster and transposon Tn1549 was found in clonally unrelated VanB-type vancomycin-resistant Enterococcus spp. strains isolated in France. The transposon was chromosomally located or plasmid borne...

..have been detected and are mainly encoded by mobile genetic elements...

..The aadD2 gene was chromosomally located in all strains and was not transferable by conjugation. These data indicate that chromosomal aadD2 is specific to B. clausii...

..aureus strains and demonstrated increased colonization levels by MRSA in cystic fibrosis transmembrane conductance regulator-deficient mice and Toll-like receptor 2 (TLR2)-deficient mice but not TLR4-deficient mice...

..The sequences of the promoter regions and of the structural genes for 13 penicillinase, extended-spectrum, and inhibitor-resistant TEM-type beta-lactamases have been determined, and an updated blaTEM gene nomenclature is proposed...

..coli and streptothricin producers Streptomyces lavendulae and Streptomyces noursei. The sat4 gene was detected by hybridization in clinical and environmental isolates of Campylobacter spp...

..haemolyticus BM4610. The two enzymes are 161 amino acids long and differ by 14 amino acid substitutions...

..Thus, VanX and VanY had non-overlapping functions involving the hydrolysis of D-Ala-D-Ala and the removal of D-Ala from membrane-bound lipid intermediates respectively...

..The MICs of gentamicin against these strains of S. maltophilia were lower than those of amikacin, netilmicin, and tobramycin, indicating that production of AAC(6')-Iz contributes to aminoglycoside resistance in S. maltophilia...

..Solvent kinetic isotope effects on V/K were normal for the WT enzyme and inverse for the double mutant. We discuss a chemical mechanism and the likely rate-limiting steps for both the wild-type and mutant forms of the enzyme...

..Activation of the VanR response regulator in the absence of VanS may involve autophosphorylation of VanR with acetyl phosphate or phosphorylation by a heterologous histidine protein kinase...

..faecium BM4339, the only VanD-type strain described so far, BM4416 produced an impaired D-alanine:D-alanine ligase. Unlike for BM4339, which had a 5-bp insertion in ddl, inactivation of the gene in BM4416 was due to insertion of IS19...

..The corresponding genes were found to be adjacent as the result of a recombination event between Tn4001 and Tn5405, two transposons originating in staphylococci...

..Expression of the acquired genes occurs in both dividing and quiescent cells. The only requirement for bacteria to transfer genetic material into nonprofessional phagocytic cells and macrophages is the ability to invade the host cell...

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..Differences at the regulatory level accounted for phenotypic diversity in acquired glycopeptide resistance by production of D-lac-ending precursors...

..Sequential acquisition of mutations in parE and gyrA leads to higher levels of resistance. This confirms that topoisomerase IV is the primary target of fluoroquinolones in S. pneumoniae...

..Spectinomycin resistance in clinical isolates of Neisseria meningitidis and Neisseria gonorrhoeae was found to be due to mutations G1064C and C1192U (Escherichia coli numbering) in 16S rRNA genes, respectively...

..This new type of glycopeptide resistance phenotype was designated VanD...

..It thus appears that posttranscriptional modification of 16S rRNA confers high-level resistance to all the clinically available aminoglycosides except streptomycin in gram-negative human and animal pathogens...

..In each of these methods, vancomycin was more efficient than teicoplanin for detecting glycopeptide resistance...

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..Results of primer extension experiments indicated that ISEcp1 provides the promoter for expression of bla(CTX-M-17) and may contribute to dissemination of this gene...

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..The occurrence of this DNA rearrangement, which did not involve homologous sequences, suggests that the In40 integrase could promote recombination at secondary sites...

..pneumoniae and N. meningitidis...

..The occurrence of this motif, possibly a recombination site which would have allowed the association of units of separate functions, is compatible with a modular concept for the structure of aminoglycoside-modifying enzymes...