In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation

In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation
Title:
In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation
Other Titles:
International Journal of Molecular Sciences
Publication Date:
14 November 2020
Citation:
Thappeta, K.R.V.; Zhao, L.N.; Nge, C.E.; Crasta, S.; Leong, C.Y.; Ng, V.; Kanagasundaram, Y.; Fan, H.; Ng, S.B. In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation. Int. J. Mol. Sci. 2020, 21, 8601. https://doi.org/10.3390/ijms21228601
Abstract:
Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA. These compounds also significantly reduced the growth of S. aureus but possessed moderate mammalian toxicity. Furthermore, S. aureus strains treated with these compounds exhibited reduction in adherence to host fibrinogen, as well as biofilm formation. Hence, these compounds may represent an anti-infective therapy without the side effects of antibiotics.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research is supported by core funding from: Singapore Institute of Food and Biotechnology Innovation (SIFBI)
Grant Reference no. :

This research is supported by core funding from: Bioinformatics Institute (BII)
Grant Reference no. :

This research is supported by core funding from: Biomedical Research Council (BMRC) Transition Fund
Grant Reference no. : H16/99/b0/004
Description:
ISSN:
1661-6596
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