- Klíčová slova
- nafithromycin,
- MeSH
- antibakteriální látky MeSH
- ketolidy * chemie terapeutické užití MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
Staphylococcus aureus is one of the most important pathogens causing chronic biofilm infections. These are becoming more difficult to treat owing to drug resistance, particularly because S. aureus biofilms limit the efficacy of antimicrobial agents, leading to high morbidity and mortality. In the present study, we screened for inhibitors of S. aureus biofilm formation using a natural product library from the Korea Chemical Bank (KCB). Screening by crystal violet-based biomass staining assay identified hit compounds. Further examination of antibiofilm properties of these compounds was conducted and led to the identification of celastrol and telithromycin. In vitro, both celastrol and telithromycin were toxic to planktonic S. aureus and also active against a clinical methicillin-resistant S. aureus (MRSA) isolate. The effect of the compounds on preformed biofilms of clinical MRSA isolates was evaluated by confocal laser scanning microscopy (CLSM), which revealed the absence of typical biofilm architecture. In addition, celastrol and telithromycin inhibited the production of extracellular protein at selected sub-MIC concentrations, which revealed the reduced extracellular polymeric substance (EPS) secretion. Celastrol exhibited greater cytotoxicity than telithromycin. These data suggest that the hit compounds, especially telithromycin, could be considered novel inhibitors of S. aureus biofilm. Although the mechanisms of the effects on S. aureus biofilms are not fully understood, our data suggest that telithromycin could be a useful adjuvant therapeutic agent for S. aureus biofilm-related infections.
- MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy účinky léků růst a vývoj MeSH
- biologické přípravky farmakologie MeSH
- genciánová violeť MeSH
- ketolidy farmakologie MeSH
- knihovny malých molekul farmakologie MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků fyziologie MeSH
- mikrobiální testy citlivosti MeSH
- plankton účinky léků růst a vývoj MeSH
- rychlé screeningové testy MeSH
- Staphylococcus aureus účinky léků fyziologie MeSH
- triterpeny farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
The ABCF family protein Msr(A) confers high resistance to macrolides but only low resistance to ketolides in staphylococci. Mutations in conserved functional regions of ClpX as well as deletion of clpX significantly increased Msr(A)-mediated resistance to the ketolide antibiotic telithromycin. ClpX is the chaperone component of the ClpXP two-component proteolytic system. Nevertheless, no changes in resistance were observed in a clpP knockout strain expressing msr(A), demonstrating that ClpX affects Msr(A) independently of ClpP.
Přirozená makrolidová antibiotika jsou postupně nahrazována semisyntetickými přípravky, které mají výhodnější vlastnosti. Při shodném antimikrobiálním působení jsou jednotlivé dávky menší, dávkovací intervaly delší, lépe je snáší i dětská populace a méně často dochází k nežádoucímu působení. Nevhodně zvolená antibiotika, nesprávné dávkování a nevhodné indikace zvyšují však riziko narůstání rezistence běžných bakteriálních patogenů. Makrolidy jsou vynikající léky pro ambulantní praxi. Aby zůstaly stále účinné, je nutné zahájit léčbu u správně indikovaných infekcí, zvolit vhodnou dávku, stanovit dávkovací intervaly i celkové trvání léčby.
Natural macrolide antibiotics are gradually replaced by semisynthetic preparations with superior properties. While having comparable antimicrobial action, the latter require lower single doses and longer dosage intervals, are better tolerated by the paediatric population, and induce adverse effects less frequently. Inappropriate selection of antibiotics, incorrect dosage, and improper indications, however, increase the risk of increasing resistance in common bacterial pathogens. Macrolides are excellent drugs for ambulatory practice. For them to remain effective, treatment needs to be initiated for properly indicated infections, correct dosage needs to be chosen, and dosage intervals as well as duration of treatment determined.
- MeSH
- antibiotická rezistence MeSH
- azithromycin aplikace a dávkování terapeutické užití MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- erythromycin aplikace a dávkování terapeutické užití MeSH
- ketolidy terapeutické užití MeSH
- klarithromycin aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- lymeská nemoc farmakoterapie MeSH
- makrolidy dějiny farmakokinetika terapeutické užití MeSH
- mladiství MeSH
- novorozenec MeSH
- roxithromycin aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
We determined the activities of new antibiotics telithromycin (ketolide) and quinupristin/dalfopristin (streptogramins) against 88 macrolide and/or lincosamide resistant coagulase-negative staphylococci (CoNS) isolates with defined resistance gene status. Telithromycin susceptibility was determined only in erythromycin-sensitive isolates (15) indicating the same mechanisms of resistance. In contrast, all erythromycin-resistant isolates (73) were either constitutively resistant to telithromycin (13 isolates with constitutive erm genes) or demonstrated telithromycin D-shaped zone (60 isolates with inducible msr(A) and/or erm). However, the level of inducible resistance conferred by msr(A) (35 isolates) was borderline even after induction by erythromycin. No quinupristin/dalfopristin resistant isolate was observed if tested by disk-diffusion method (DDM) but 18 isolates were intermediate (MIC = 1-3 mg/L) and two isolates resistant (MIC = 8 mg/L) if tested by E-test. All these isolates were resistant to streptogramin A and harbored vga(A) gene (1 isolate) or vga(A)LC gene (19 isolates). MICs for quinupristin/dalfopristin were higher for isolates with combination of streptogramin A resistance and constitutive MLSB resistance (MIC = 3-8 mg/L in 4 isolates) than for streptogramin A-resistant isolates susceptible to streptogramin B (MIC = 0.5-2 mg/L in 16 isolates). In addition to S. haemolyticus, vga(A)LC was newly identified in S. epidermidis and S. warnerii indicating its widespread occurrence in CoNS. Misidentification of low-level resistant isolates by DDM may contribute to dissemination of streptogramin A resistance.
- MeSH
- financování organizované využití MeSH
- infekce spojené se zdravotní péčí genetika imunologie MeSH
- ketolidy imunologie metabolismus MeSH
- koagulasa MeSH
- polymerázová řetězová reakce využití MeSH
- rezistence na methicilin genetika imunologie účinky léků MeSH
- Staphylococcus genetika imunologie účinky léků MeSH
- streptograminy izolace a purifikace MeSH
- virginiamycin imunologie metabolismus MeSH
