Targeting N-acetylglucosaminidase in Staphylococcus aureus with iminosugar inhibitors

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

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.

• Language: English
• Keywords: autolysin E, glycoside hydrolase, iminosugars, surface plasmon resonance, enzyme inhibition
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 12 str.
• Numbering: Vol. 13, iss. 8, art. 751
• PID: 20.500.12556/RUL-160064
• UDC: 615.015.8
• ISSN on article: 2079-6382
• DOI: 10.3390/antibiotics13080751
• COBISS.SI-ID: 204113923
• Publication date in RUL: 14.08.2024

Record is a part of a journal

• Title: Antibiotics
• Shortened title: Antibiotics
• Publisher: MDPI
• ISSN: 2079-6382
• COBISS.SI-ID: 522975769

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: avtolizin E, glikozid hidrolaza, iminosladkorji, površinska plazmonska resonanca, zaviranje encimov, bakterijska rezistenca

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0017
• Name: Modeliranje kemijskih procesov in lastnosti spojin

• Funder: Other - Other funder or multiple funders
• Project number: 39008
• Name: Young researchers fund