Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00553394" target="_blank" >RIV/61388971:_____/22:00553394 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/86652036:_____/22:00553394 RIV/61389013:_____/22:00553394
Výsledek na webu
<a href="https://www.mdpi.com/1422-0067/23/1/97" target="_blank" >https://www.mdpi.com/1422-0067/23/1/97</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms23010097" target="_blank" >10.3390/ijms23010097</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics
Popis výsledku v původním jazyce
Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin, however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Clostridium difficile. The expression of vancomycin Z (vanZ), encoded either in the vancomycin A (vanA) glycopeptide antibiotic resistance gene cluster or in the genomes of E. faecium, as well as Streptococcus pneumoniae and C. difficile, was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from E. faecium EnGen0191 was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo.
Název v anglickém jazyce
Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics
Popis výsledku anglicky
Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin, however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Clostridium difficile. The expression of vancomycin Z (vanZ), encoded either in the vancomycin A (vanA) glycopeptide antibiotic resistance gene cluster or in the genomes of E. faecium, as well as Streptococcus pneumoniae and C. difficile, was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from E. faecium EnGen0191 was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
International Journal of Molecular Sciences
ISSN
1422-0067
e-ISSN
1422-0067
Svazek periodika
23
Číslo periodika v rámci svazku
1
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
17
Strana od-do
97
Kód UT WoS článku
000751085700001
EID výsledku v databázi Scopus
2-s2.0-85121439722