Antimikrobna aktivnost halkona i in vitro uticaj na fiziološko-biohemijske karakteristike i ekspresiju faktora virulencije meticilin-rezistentnih sojeva Staphylococcus aureus
Antimicrobial activity of chalcones and in vitro effect on physiological and biochemical characteristics and expression of virulence factors of methicillin - resistant Staphylococcus aureus
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Uvod: Meticilin-rezistentan S. aureus (MRSA) je jedan od glavnih izazivača
intrahospitalnih infekcija sa čestim letalnim ishodom i infekcija kod mladih i zdravih
ljudi koji dolaze iz vanbolničke sredine. Brz razvoj rezistencije stafilokoka na nove
antimikrobne agense i interhumano širenje rezistentnih sojeva su glavni terapijski
problemi današnjice. Iz tog razloga je neophodno razviti nove agense koji bi imali
primenu u prevenciji ili lečenju stafilokoknih infekcija. Halkoni spadaju u grupu
flavonoida, jedinjenja koja se mogu izolovati iz prirodnih izvora kao što su biljke, voće
i povrće ili se dobiti metodama klasične i kombinatorne sinteze. Hemijska struktura
halkona se sastoji od dva aril prstena koja su povezana α,β-nezasićenim ketonom.
Dosadašnja istraživanja su pokazala da različiti halkoni ispoljavaju širok spektar
bioloških aktivnosti, kao što su antibakterijska, antivirusna, antigljivična, antiangiogena,
antitumorska, antiproliferativna i antiinflamatorna aktivnost.
Ciljevi is...traživanja: Osnovni cilj istraživanja je bilo ispitivanje osetljivosti genotipski i
fenotipski heterogenih MRSA sojeva na tri sintetisana halkona: Bis-(2-hydroxyphenyl)-
propenona (u daljem tekstu O-OH), 3-(3-Hydroxy-phenyl)-1-(2-hydroxyphenyl)-
propenona (u daljem tekstu M-OH) i 3-(4-Hydroxy-phenyl)-1-(2-hydroxyphenyl)-
propenona (u daljem tekstu P-OH) i ispitivanje in vitro uticaja halkona na
biohemijsko-fiziološke osobine MRSA sojeva, ekspresiju faktora virulencije
(produkciju glikokaliksa, produkciju biofilma i vezivanje za humani fibronektin) i
produkciju stafilokoknih hemolizina. Takoñe je izvršeno i ispitivanje efekta
kombinovane primene halkona i antibiotika sa različitim mehanizmima delovanja na
rast izolovanih MRSA sojeva.
Materijal i metode: Izolovani sojevi S. aureus su identifikovani kao MRSA pomoću
konvencionalnih metoda, komercijalnim automatizovanim sistemom (VITEK 2 ID
karticama) i molekularnim metodama (PCR metod - detekcija nuc i mecA gena).
Genotipizacija izolovanih MRSA sojeva je izvršena različitim PCR protokolima na
osnovu čega su MRSA sojevi klasifikovani u različite SCCmec tipove, agr tipove, spa
tipove i grupisani u spa klonske komplekse...
Introduction: Staphylococcus aureus is potentially pathogenic bacterium that causes a
broad spectrum of diseases, ranging from minor infections of the skin and soft tissue in
the community, to severe nosocomial infections like endocarditis, bacteremia and
sepsis. Multiresistance of methicillin-resistant S.aureus (MRSA) is one of the most
serious therapeutical problems nowadays, and requires urgent development of new
antibacterial compounds. Chalcones belong to a group of naturally occurring flavonoids
with chemical structure made of two aryl rings linked by a α,β-unsaturated ketone.
Although these compounds are usually isolated from various plant species, they can also
be obtained by the methods of classical and combinatorial synthesis. Chalcones are
compounds with potent biological activities, amongst which are antibacterial, antiviral,
antifungal, antiproliferative and antiinflammatory.
The aim of the study: The goal of this study was to evaluate the antibacterial effect of
three new...ly-synthesized chalcones: 1,3- Bis-(2-hydroxy-phenyl)-propenone (further
referred as O-OH), 3-(3-hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone (further
referred as M-OH) and 3-(4-hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone (further
referred as P-OH) against genetically diverse clinical isolates of MRSA, and the effect
on physiological and biochemical characteristics and expression of virulence factors
(production of glycocalyx, biofilm and adherence to human fibronectin) and production
of α-hemolysin of these bacteria. One of the aims of this study was also to investigate
the synergism of chalcones with various β-lactam and non- β-lactam antibiotics.
Methods:
Clinical isolates of S. aureus were identified as MRSA with classical methods,
commercial automated microbiological identification system (VITEK 2 ID test cards)
and molecular methods (PCR method for detection of nuc and mecA gene). Genotyping
of MRSA was performed with adequate PCR protocols for the detection of SCCmec
type, agr type, Panton-Valentin leucocidin (PVL) gene and spa type. Different spa
types were clustered into spa clonal complexes (CC)...
Faculty:
Универзитет у Београду, Фармацеутски факултетDate:
05-06-2014Projects:
- Antibiotic resistant bacterial pathogens in Serbia: phenotypic and genotypic characterization (RS-175039)