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  • 1
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A Staphylococcus epidermidis plasmid conferring inducible resistance to 14-membered ring macrolides and type B streptogramins has been analysed and the DNA sequence of the gene responsible for resistance determined. A single open reading frame of 1.464kbp, preceded by a complex control region containing a promoter and two ribosomal binding sites, was identified. The deduced sequence of the 488-amino-acid protein (MsrA) revealed the presence of two ATP-binding motifs homologous to those of a family of transport-related proteins from Gram-negative bacteria and eukaryotic cells, including the P-glycoprotein responsible for multidrug resistance. In MsrA, but not these other proteins, the two potential ATP-binding domains are separated by a Q-linker of exceptional length. Q-linkers comprise a class of flexible inter-domain fusion junctions that are typically rich in glutamine and other hydrophilic amino acids and have a characteristic spacing of hydrophobic amino acids, as found in the MsrA sequence. Unlike the other transport-related proteins, which act in concert with one or more hydrophobic membrane proteins, MsrA appears to function independently when cloned in a heterologous host (Staphylococcus aureus RN4220). MsrA might, therefore, interact with and confer antibiotic specificity upon other transmembrane efflux complexes of staphylococcal cells. The active efflux of [14C]-erythromycin from cells of S. aureus RN4220 containing msrA has been demonstrated.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Twenty-five previously untreated acne patients were monitored throughout a 6-month course of therapy with either tetracycline or minocycline for changes in the numbers of staphylococci, propionibacteria and yeasts of the genus Malessezia on the skin surface. Antibiotic resistant staphylococci and propionibacteria were also counted. Minocycline (50 mg b.d.) produced a 10-fold greater reduction in propionibacterial numbers compared to tetracycline (500 mg b.d.) after 12 (P 〈 0.02, t-test) and 24 weeks (P 〈 0.05) of therapy. As treatment progressed, propionibacteria were replaced by yeasts, numbers of which were significantly increased by week 12 (P 〈 0.02) in tetracycline-treated patients and by week 24 (P 〈 0.01) in minocycline-treated patients. This suggests that yeasts have no role in the pathogenesis of acne but may compete with propionibacteria for the same niche. Overgrowth of antibiotic resistant staphylococci prevented any decrease in staphylococcal numbers in tetracycline-treated patients, but minocycline produced a significant and sustained reduction in staphylococcal numbers after 1 week of therapy (P 〈 0.001). An increase in the number of multiply resistant (〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:00070963:BJD233:ges" location="ges.gif"/〉 3 resistances) staphylococci occurred in 67% of tetracycline-treated and 33% of minocycline-treated patients by the end of the treatment period. There was no evidence of propionibacterial resistance in either treatment group. This study shows that minocycline has much greater antibacterial activity in vivo against both staphylococci and propionibacteria and produces less staphylococcal antibiotic resistance than tetracycline.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract A gene (ertX) encoding a putative ABC transporter was cloned from the erythromycin producer Saccharopolyspora erythraea, using PCR. The primers were based on regions of homology from ABC transporters which confer resistance to macrolide antibiotics. While ertX encodes a protein with a strong degree of similarity to other macrolide ABC transporters from streptomycetes and staphylococci, it did not confer resistance to erythromycin, tylosin, spiramycin, oleandomycin, josamcin, chalcomycin or midecamycin when subcloned into sensitive streptomycete hosts. Southern blot analysis suggested that ertX did not constitute part of the erythromycin gene cluster as identified to date.
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  • 5
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a 〉 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P 〈 0.001, Wilcoxon's matched pairs) and also significantly reduced the number of erythromycin-resistant propionibacteria (P 〈 0.05). In contrast, erythromycin alone reduced the total propionibacterial count by 〈 1.5 log10 c.f.u./cm2 after 6 weeks (P 〈 0.05) and did not affect the number of erythromycin-resistant strains. The combined formulation was significantly more effective at reducing total propionibacterial numbers at 6 (P 〈 0.01, Mann-Whitney) and 12 weeks (P 〈 0.05) than erythromycin alone, although, after 12 weeks, the anti-propionibacterial efficacy of both preparations was less marked. Five patients on combination therapy, and five treated with erythromycin alone, acquired erythromycin-resistant strains de novo at week 6 or week 12. In an open study in 21 acne patients, who each carried 〉 103 c.f.u. erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by 〉 2.5 log10 and the number of erythromycin-resistant strains by a similar amount (P 〈 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P 〈 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo antipropionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant propionibacterial strains pretreatment.
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