A Spectrum of Changes Occurs in Peptidoglycan Composition of Glycopeptide-Intermediate Clinical Staphylococcus aureus Isolates

Abstract

The mechanism of glycopeptide resistance in Staphylococcus aureus is not known with certainty. Because the target of vancomycin is the D-Ala-D-Ala terminus of the stem peptide of the peptidoglycan precursor, by subjecting muropeptides to reversed-phase high-performance liquid chromatography, we investigated peptidoglycan obtained from glycopeptide-intermediate S. aureus (GISA) isolates for changes in composition and evaluated whether any peptidoglycan structural change was a consistent feature of clinical GISA isolates. GISA isolates Mu50 and Mu3 from Japan had the large glutamate-containing monomeric peak demonstrated previously, although strain H1, a vancomycin-susceptible MRSA isolate from Japan that was clonally related to Mu3 and Mu50, and a femC mutant that we studied, did also. For the U.S. GISA isolates, strain NJ had a large monomeric peak with a retention time identical to that described for the glutamate-containing monomer in strains H1, Mu3, and Mu50. However, a much smaller corresponding peak was seen in GISA MI, and this peak was absent from both GISA PC and a recent GISA isolate obtained from an adult patient in Illinois (strain IL). These data suggest that a uniform alteration in peptidoglycan composition cannot be discerned among the GISA isolates and indicate that a single genetic or biochemical change is unlikely to account for the glycopeptide resistance phenotype in the clinical GISA isolates observed to date. Furthermore, a large monomeric glutamate-containing peak is not sufficient to confer the resistance phenotype.

Staphylococcus aureus resistente a vancomicina.

“…En ambas cepas la expresión de PBP4, una carboxipeptidasa y transpeptidasa secundaria que se requiere para el (43). Aunque las hipótesis mencionadas explican parcialmente el mecanismo de resistencia a vancomicina, se han aislado unas pocas cepas VISA que no tienen estas alteraciones en la pared celular, lo que hace pensar que la resistencia debe obedecer a mecanismos alternativos aún sin estudiar (44).…”

Study of Photosensitizer for Antibacterial Photodynamic Therapy Based on Cyclodextrin Formulation of 133-N-(N-Methylnicotinyl)bacteriopurpurinimide Methyl Ester

“…Каприн, Е.В. Филоненко Исследование фотосенсибилизатора для антибактериальной фотодинамической терапии на основе циклодекстриновой композиции метилового эфира 13 3 …”

“…Pharmacokinetics and biodistribution of PS were studies in vivo in organs and tissues of intact mice and septic wounds infected with P. аeruginosa or S. aureus. The preliminary studies have shown high efficiency of antimicrobial photodynamic therapy of septic wounds with cyclodextrin dispersion of 13 3 -N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester. Results of study of absorption and spectral and fluorescence properties of its drug formulation depending on its composition allowed to recommend the use of weight ratio 13 3 -N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester : cyclodextrin about 1:200 and addition of 0,1% Tween 80 to reduce aggregation.…”

“…The preliminary studies have shown high efficiency of antimicrobial photodynamic therapy of septic wounds with cyclodextrin dispersion of 13 3 -N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester. Results of study of absorption and spectral and fluorescence properties of its drug formulation depending on its composition allowed to recommend the use of weight ratio 13 3 -N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester : cyclodextrin about 1:200 and addition of 0,1% Tween 80 to reduce aggregation. The study showed that 13 3 -N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester was rapidly cleared from mouse blood circulation: more than 70% -for 2 h, 95% -for 1 day, more than 99% -for 6 days.…”

“…The irradiation 2 h after injection provided high efficacy of the therapy of septic wounds. Key words: antibacterial photodynamic therapy, 13 3 -N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester, bacteriochlorine derivative, absorption, fluorescence, aggregation, cyclodextrin.…”