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B. Berger-bächi - One of the best experts on this subject based on the ideXlab platform.

  • A novel DNA-binding protein modulating Methicillin Resistance in staphylococcus aureus
    BMC microbiology, 2009
    Co-Authors: Miriam Ender, B. Berger-bächi, Nadine Mccallum
    Abstract:

    Methicillin Resistance in Staphylococcus aureus is conferred by the mecA-encoded penicillin-binding protein PBP2a. Additional genomic factors are also known to influence Resistance levels in strain specific ways, although little is known about their contribution to Resistance phenotypes in clinical isolates. Here we searched for novel proteins binding to the mec operator, in an attempt to identify new factor(s) controlling Methicillin Resistance phenotypes. Analysis of proteins binding to a DNA fragment containing the mec operator region identified a novel, putative helix-turn-helix DNA-binding protein, SA1665. Nonpolar deletion of SA1665, in heterogeneously Methicillin resistant S. aureus (MRSA) of different genetic backgrounds, increased Methicillin Resistance levels in a strain dependent manner. This phenotype could be fully complemented by reintroducing SA1665 in trans. Northern and Western blot analyses, however, revealed that SA1665 had no visible influence on mecA transcription or amounts of PBP2a produced. SA1665 is a new chromosomal factor which influences Methicillin Resistance in MRSA. Although SA1665 bound to the mecA promoter region, it had no apparent influence on mecA transcription or translation, suggesting that this predicted DNA-binding protein modulates Resistance indirectly, most likely through the control of other genomic factors which contribute to Resistance.

  • Factors influencing Methicillin Resistance in staphylococci.
    Archives of microbiology, 2002
    Co-Authors: B. Berger-bächi, Susanne Rohrer
    Abstract:

    Methicillin Resistance in staphylococci is due to an acquired penicillin-binding protein, PBP2' (PBP2a). This additional PBP, encoded by mecA, confers an intrinsic Resistance to all beta-lactams and their derivatives. Resistance levels in Methicillin-resistant Staphylococcus aureus (MRSA) depend on efficient PBP2' production and are modulated by chromosomal factors. Depending on the genetic background of the strain that acquired mecA, Resistance levels range from phenotypically susceptible to highly resistant. Characteristic for most MRSA is the heterogeneous expression of Resistance, which is due to the segregation of a more highly resistant subpopulation upon challenge with Methicillin. Maximal expression of Resistance by PBP2' requires the efficient and correct synthesis of the peptidoglycan precursor. Genes involved in cell-wall precursor formation and turnover, regulation, transport, and signal transduction may determine the level of Resistance that is expressed. At this stage, however, there is no information available on the functionality or efficacy of such factors in clinical isolates in relation to Methicillin Resistance levels.

  • Genetic basis of Methicillin Resistance in Staphylococcus aureus
    Cellular and Molecular Life Sciences, 1999
    Co-Authors: B. Berger-bächi
    Abstract:

    Methicillin Resistance in staphylococci is due to the acquisition of the mecA gene encoding a new penicillin-binding protein (PBP2′, PBP2a) that has a lower affinity to Methicillin than the endogenous PBPs. PBP2′ is involved in the assembly of the cell wall peptidoglycan in the presence of high concentrations of β-lactams that otherwise inhibit the endogenous PBPs. The production of PBP2′ is under dual control by its own mecR1-mecI- and the penicillinase blaR1-blaI-encoded regulatory elements. Resistance to high levels of Methicillin depends, in addition to PBP2′, on chromosomally encoded factors that are involved in the synthesis and degradation of the peptidoglycan. Any mutations that reduce peptidoglycan precursor formation or change the chemical composition of the muropeptide precursor result in lowered Resistance.

  • Role of fem factors in Methicillin Resistance
    Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 1998
    Co-Authors: B. Berger-bächi, Martin Tschierske
    Abstract:

    Methicillin Resistance in Staphylococcus aureus is primarily due to the acquisition of an additional penicillin-binding protein, PBP2' (also known as PBP2a), that confers Resistance to virtually all beta-lactam antibiotics. This foreign PBP2' has strict requirements on peptidoglycan precursor formation and composition in order to function optimally. The level of Methicillin Resistance is governed by genomic factors which are involved in cell wall metabolism and/or are constituents of the cytoplasmic membrane. The formation of the pentaglycine interpeptide bridge of peptidoglycan plays a key function and depends on at least three factors, FemX, FemA and FemB.

  • Impact of sar and agr on Methicillin Resistance in Staphylococcus aureus.
    FEMS microbiology letters, 1996
    Co-Authors: S.piriz Duran, F H Kayser, B. Berger-bächi
    Abstract:

    The global regulators agr and sar control expression of cell wall and extracellular proteins. Inactivation of either sar and/or agr in a typical heterogeneously Methicillin-resistant Staphylococcus aureus resulted in a small but reproducible decrease in the number of cells in the subpopulation expressing high Methicillin Resistance. The amount of low affinity penicillin-binding protein PBP2′, the prerequisite for Methicillin Resistance, was apparently not affected, however, a reduction in PBP1 and PBP3 production was observed, suggesting that these resident PBPs of the cells might be involved somehow together with PBP2′ in high level Methicillin Resistance.

J. Etienne - One of the best experts on this subject based on the ideXlab platform.

  • Methicillin Resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia--results of a prospective observational study.
    Clinical Microbiology and Infection, 2013
    Co-Authors: N. Sicot, N. Khanafer, V. Meyssonnier, O. Dumitrescu, A. Tristan, M. Bes, G. Lina, F. Vandenesch, P. Vanhems, J. Etienne
    Abstract:

    Staphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton-Valentine leucocidin (PVL). NP was initially described for Methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with Methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of Methicillin Resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to Methicillin Resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of Methicillin Resistance. By Cox regression analysis, Methicillin Resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that Methicillin Resistance is not associated with the severity of staphylococcal necrotizing pneumonia.

  • Methicillin Resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study
    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2012
    Co-Authors: N. Sicot, N. Khanafer, V. Meyssonnier, O. Dumitrescu, M. Bes, G. Lina, F. Vandenesch, P. Vanhems, Anne Tristan, J. Etienne
    Abstract:

    Staphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton-Valentine leucocidin (PVL). NP was initially described for Methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with Methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of Methicillin Resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to Methicillin Resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of Methicillin Resistance. By Cox regression analysis, Methicillin Resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that Methicillin Resistance is not associated with the severity of staphylococcal necrotizing pneumonia.

S.c. Sanyal - One of the best experts on this subject based on the ideXlab platform.

  • Rapid detection of Methicillin Resistance in staphylococci using a slide latex agglutination kit
    International journal of antimicrobial agents, 2000
    Co-Authors: Edet E. Udo, E.m. Mokadas, A.m. Al-haddad, Bindu Mathew, L.e. Jacob, S.c. Sanyal
    Abstract:

    The slide latex agglutination test, MRSA-Screen, was compared with the mecA polymerase chain reaction (PCR) and traditional susceptibility test methods for the detection of Methicillin Resistance in Staphylococcus aureus and coagulase-negative staphylococci. The MRSA-Screen test detected the same number of Methicillin-resistant S. aureus as the mecA PCR and the traditional susceptibility tests. It correctly identified all 21 Methicillin-susceptible S. aureus as being sensitive. It also produced the same result as the mecA PCR in identifying a Methicillin-resistant S. aureus among six isolates classified as borderline resistant by traditional susceptibility tests. The MRSA-Screen test and mecA PCR detected Methicillin Resistance in 10 and 15 of 17 Methicillin-resistant coagulase-negative staphylococci, respectively. From these results, it is concluded that the MRSA-Screen is a very accurate, reliable and rapid method of detecting Methicillin Resistance in S. aureus and is suitable for use in clinical microbiology laboratories. Further study of its use in detecting Methicillin Resistance in coagulase-negative staphylococci is required.

Alexander Tomasz - One of the best experts on this subject based on the ideXlab platform.

  • inactivation of the Methicillin Resistance gene meca in vancomycin resistant staphylococcus aureus
    Microbial Drug Resistance, 1999
    Co-Authors: Krzysztof Sieradzki, Alexander Tomasz
    Abstract:

    ABSTRACT Acquisition of high-level Resistance to vancomycin in the laboratory mutant VM50 (vancomycin MIC increased from 1.5 to 100 μg/ml) was accompanied by the appearance of a heterogeneous phenotype and a virtual loss in Methicillin Resistance: in most cells of cultures of VM50 the Methicillin MIC of the parental strain was reduced from 800 to 1.5 μg/ml with only a subpopulation (10−5) retaining Methicillin Resistance at near the parental level (MIC of 400 μg/ml). Interestingly, the vancomycin MIC of this subpopulation was less (25 μg/ml) than that of VM50 (100 μg/ml). A similar antagonism between Methicillin and vancomycin Resistance levels was observed upon introduction of an intact mecA into VM50 on a plasmid vector: Methicillin Resistance of the majority of cells increased from 1.5 to 100 μg/ml while the vancomycin MIC declined from 100 to 12/25 μg/ml. Membrane preparations from mutant VM50 showed no detectable penicillin-binding protein (PBP) 2A by the fluorographic assay. Sequencing of the mecA g...

  • Molecular aspects of Methicillin Resistance in Staphylococcus aureus
    The Journal of antimicrobial chemotherapy, 1994
    Co-Authors: Hermínia De Lencastre, Boudewijn L. M. De Jonge, Peter Matthews, Alexander Tomasz
    Abstract:

    All clinical Methicillin-resistant Staphylococcus aureus (MRSA) isolates examined so far contain the mecA gene, a 2130bp stretch of DNA of non-staphylococcal origin which, together with a larger block (up to 40-60 Kb) of 'foreign' DNA, is incorporated into the staphylococcal chromosome. mecA encodes for the 78 Kd penicillin-binding protein (PBP) 2A, which has very low affinity for beta-lactam antibiotics. The sequence of the mecA gene contains structural motifs characteristic of cell wall synthetic transpeptidases. It is generally assumed that the mecA gene product (PBP 2A) acts as a surrogate enzyme which takes over the task of cell wall synthesis from the normal complement of staphylococcal PBPs, since the latter are inhibited by relatively low (e.g. Methicillin) concentrations of beta-lactam antibiotics. While direct biochemical evidence for a transpeptidase activity in PBP 2A is still missing, the essentiality of an intact mecA gene for the expression of high-level Methicillin Resistance has been clearly established by transposon inactivation experiments. On the other hand, it was already noted some time ago that an intact mecA and its gene product PBP 2A alone cannot be fully in control of the resistant phenotype, since all MRSA isolates, irrespective of their MIC values (from as low as 3 mg/L or as high as 1600 mg/L), were found to contain comparable amounts of PBP 2A. Such major disparities between cellular amounts of PBP 2A and the antibiotic MIC values suggested that a factor or factors of unknown nature ('factor X') other than the mecA gene product also played an essential role in the phenotypic expression of Resistance. The same conclusion was reached in early genetic studies in which Methicillin Resistance could be reduced by insertional inactivation of a chromosomal site (omega 2003) within the so-called femA gene--(factor essential for the expression of Methicillin Resistance) outside the mecA determinant. More recently, several additional chromosomal sites were identified outside the mecA gene in which transposon inactivation reduced the level of beta-lactam Resistance. The importance of these genes becomes clear if one realizes that it is the appropriate functioning of these determinants (in the genetic background of MRSA) rather than the quantity of PBP 2A in the cells that seems to determine the MIC value of an MRSA isolate. It is not clear at the present time how many such 'auxiliary genes' exist and exactly how these gene co-operate with the mecA gene in bringing about high-level beta-lactam Resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Jan Kluytmans - One of the best experts on this subject based on the ideXlab platform.

  • rapid slide latex agglutination test for detection of Methicillin Resistance in staphylococcus aureus
    Journal of Clinical Microbiology, 1999
    Co-Authors: Arjanne Van Griethuysen, Miranda Pouw, Nan Van Leeuwen, Max Heck, Piet Willemse, Anton Buiting, Jan Kluytmans
    Abstract:

    The MRSA screen test (Denka Seiken Co., Ltd.), a commercially available, rapid (20-min) slide latex agglutination test for the determination of Methicillin Resistance by detection of PBP 2a in Staphylococcus aureus, was compared with the oxacillin agar screen test and PCR detection of the mecA gene. A total of 563 S. aureus isolates were tested. Two hundred ninety-six of the isolates were Methicillin-susceptible isolates from cultures of blood from consecutive patients. Also, 267 Methicillin-resistant isolates that comprised 248 different phage types were tested. Methicillin Resistance was defined as the presence of the mecA gene. Of the 267 mecA gene-positive isolates, 263 were positive by the MRSA screen test (sensitivity, 98.5%), and all the mecA-gene negative strains were negative by the MRSA screen test (specificity, 100%). The oxacillin agar screen test detected Methicillin Resistance in 250 of the mecA gene-positive isolates (sensitivity, 93.6%). The sensitivity of the MRSA screen test was statistically significantly higher than the sensitivity of the oxacillin agar screen test (P < 0.05). The MRSA screen test is a highly sensitive and specific test for the detection of Methicillin Resistance. Also, it offers results within half an hour and is easy to perform, which makes this test a valuable tool in the ongoing battle against Methicillin-resistant S. aureus.