Targeting N-acetylglucosaminidase in Staphylococcus aureus with iminosugar inhibitors

Sluga, Janja (avtor), Tomašič, Tihomir (avtor), Anderluh, Marko (avtor), Hrast, Martina (avtor), Bajc, Gregor (avtor), Sevšek, Alen (avtor), Martin, Nathaniel I. (avtor), Pieters, Roland J. (avtor), Novič, Marjana (avtor), Venko, Katja (avtor)

Bacteria are capable of remarkable adaptations to their environment, including undesirable bacterial resistance to antibacterial agents. One of the most serious cases is an infection caused by multidrug-resistant Staphylococcus aureus, which has unfortunately also spread outside hospitals. Therefore, the development of new effective antibacterial agents is extremely important to solve the increasing problem of bacterial resistance. The bacteriolytic enzyme autolysin E (AtlE) is a promising new drug target as it plays a key role in the degradation of peptidoglycan in the bacterial cell wall. Consequently, disruption of function can have an immense impact on bacterial growth and survival. An in silico and in vitro evaluation of iminosugar derivatives as potent inhibitors of S. aureus (AtlE) was performed. Three promising hit compounds (1, 3 and 8) were identified as AtlE binders in the micromolar range as measured by surface plasmon resonance. The most potent compound among the SPR response curve hits was 1, with a K$_D$ of 19 μM. The K$_D$ value for compound 8 was 88 μM, while compound 3 had a K$_D$ value of 410 μM.

• Jezik: Angleški jezik
• Ključne besede: autolysin E, glycoside hydrolase, iminosugars, surface plasmon resonance, enzyme inhibition
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 12 str.
• Številčenje: Vol. 13, iss. 8, art. 751
• PID: 20.500.12556/RUL-160064
• UDK: 615.015.8
• ISSN pri članku: 2079-6382
• DOI: 10.3390/antibiotics13080751
• COBISS.SI-ID: 204113923
• Datum objave v RUL: 14.08.2024

Gradivo je del revije

• Naslov: Antibiotics
• Skrajšan naslov: Antibiotics
• Založnik: MDPI
• ISSN: 2079-6382
• COBISS.SI-ID: 522975769

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: avtolizin E, glikozid hidrolaza, iminosladkorji, površinska plazmonska resonanca, zaviranje encimov, bakterijska rezistenca

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P1-0017
• Naslov: Modeliranje kemijskih procesov in lastnosti spojin

• Financer: Drugi - Drug financer ali več financerjev
• Številka projekta: 39008
• Naslov: Young researchers fund