The increase in antibiotic resistance among Gram-positive bacteria underscores the urgent need to develop new antibiotics. New antibiotics should target actively growing susceptible bacteria that are resistant to clinically accepted antibiotics including bacteria that are not growing or are protected in a biofilm environment. In this paper, we compare the in vitro activities of two new semisynthetic glycopeptide antibiotics, MA79 and ERJ390, with two clinically used glycopeptide antibiotics-vancomycin and teicoplanin. The new antibiotics effectively killed not only exponentially growing cells of Staphylococcus aureus, but also cells in the stationary growth phase and biofilm.

• Publikační typ
• časopisecké články MeSH

vanZ, a member of the VanA glycopeptide resistance gene cluster, confers resistance to lipoglycopeptide antibiotics independent of cell wall precursor modification by the vanHAX genes. Orthologs of vanZ are present in the genomes of many clinically relevant bacteria, including Enterococcus faecium and Streptococcus pneumoniae; however, vanZ genes are absent in Staphylococcus aureus. Here, we show that the expression of enterococcal vanZ paralogs in S. aureus increases the minimal inhibitory concentrations of lipoglycopeptide antibiotics teicoplanin, dalbavancin, oritavancin and new teicoplanin pseudoaglycone derivatives. The reduction in the binding of fluorescently labeled teicoplanin to the cells suggests the mechanism of VanZ-mediated resistance. In addition, using a genomic vanZ gene knockout mutant of S. pneumoniae, we have shown that the ability of VanZ proteins to compromise the activity of lipoglycopeptide antibiotics by reducing their binding is a more general feature of VanZ-superfamily proteins.

• Publikační typ
• časopisecké články MeSH

Here, we describe a fluorescent assay developed to study competitive binding of the glycopeptide antibiotics to live bacteria cells. This assay demonstrated that the mechanism of action of the lipoglycopeptide antibiotics strongly depends on the hydrophobicity of the substitutes, with the best antibacterial activity of the glycopeptide antibiotics equally sharing properties of binding to D-Ala-D-Ala residues of the nascent peptidoglycan and to the membrane.

• MeSH
• antibakteriální látky metabolismus   MeSH
• barvení a značení MeSH
• buněčná stěna mikrobiologie   MeSH
• Enterococcus faecium metabolismus   MeSH
• enterokoky rezistentní vůči vankomycinu metabolismus   MeSH
• fluorescence MeSH
• glykopeptidy metabolismus   MeSH
• lipoglykopeptidy chemie   metabolismus   MeSH
• mikrobiální testy citlivosti MeSH
• peptidoglykan metabolismus   MeSH
• rhodaminy chemie   MeSH
• Staphylococcus aureus metabolismus   MeSH
• teikoplanin analogy a deriváty   chemie   metabolismus   MeSH
• vankomycin chemie   metabolismus   MeSH
• vazba proteinů fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: The aim of this study was to analyse the DNA sequences of three teicoplanin-resistant Staphylococcus epidermidis isolates collected from patients not previously treated with glycopeptide antibiotics. METHODS: The minimum inhibitory concentrations (MICs) of 12 antibiotics, including teicoplanin and vancomycin, were determined by the broth microdilution method. Genomic DNA was isolated, was sequenced by HiSeqX paired-end sequencing and was assembled into draft genome sequences using MyPro pipeline. RESULTS: Analysis of the draft genome sequences demonstrated that the teicoplanin-resistant S. epidermidis isolates belonged to multilocus sequence typing (MLST) sequence types ST5 and ST87 and encoded multiple antimicrobial resistance genes, including the methicillin resistance gene mecA. CONCLUSIONS: This report highlights the risk of dissemination of S. epidermidis strains resistant to a wide range of clinically important antibiotics.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence * MeSH
• genom bakteriální * MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• multilokusová sekvenční typizace MeSH
• sekvenování celého genomu MeSH
• stafylokokové infekce mikrobiologie   MeSH
• Staphylococcus epidermidis klasifikace   účinky léků   MeSH
• techniky typizace bakterií MeSH
• teikoplanin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We investigated the genetic basis of glycopeptide resistance in laboratory-derived strains of S. haemolyticus with emphasis on differences between vancomycin and teicoplanin. The genomes of two stable teicoplanin-resistant laboratory mutants selected on vancomycin or teicoplanin were sequenced and compared to parental S. haemolyticus strain W2/124. Only the two non-synonymous mutations, VraS Q289K and WalK V550L were identified. No other mutations or genome rearrangements were detected. Increased cell wall thickness, resistance to lysostaphin-induced lysis and adaptation of cell growth rates specifically to teicoplanin were phenotypes observed in a sequenced strain with the VraS Q289K mutation. Neither of the VraS Q289K and WalK V550L mutations was present in the genomes of 121S. haemolyticus clinical isolates. However, all but two of the teicoplanin resistant strains carried non-synonymous SNPs in vraSRTU and walKR-YycHIJ operons pointing to their importance for the glycopeptide resistance.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence genetika   MeSH
• DNA bakterií genetika   MeSH
• fenotyp MeSH
• genom bakteriální genetika   MeSH
• histidinkinasa genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• rezistence na vankomycin genetika   MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• stafylokokové infekce mikrobiologie   MeSH
• Staphylococcus haemolyticus účinky léků   genetika   izolace a purifikace   MeSH
• teikoplanin farmakologie   MeSH
• vankomycin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko MeSH

• MeSH
• bakteriální proteiny genetika   MeSH
• glykopeptidy farmakologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mikrobiální testy citlivosti MeSH
• mutace MeSH
• stafylokokové infekce mikrobiologie   MeSH
• Staphylococcus účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH