Covalent-fragment screening identifies selective inhibitors of multiple Staphylococcus aureus serine hydrolases important for growth and biofilm formation
2024

Identifying Selective Inhibitors for Staphylococcus aureus Enzymes

Sample size: 1600 publication 10 minutes Evidence: high

Author Information

Author(s): Matthew Bogyo, Tulsi Upadhyay, Emily Woods, Stephen Ahator, Kjersti Julin, Franco Faucher, Marijn Hollander, Nichole Pedowitz, Daniel Abegg, Isabella Hammond, Ifeanyichukwu Eke, Sijie Wang, Shiyu Chen, John Bennett, Jeyun Jo, Christian Lentz, Alex Adibekian, Matthias Fellner

Primary Institution: Stanford University

Hypothesis

Can a high-throughput screening approach identify selective inhibitors for Staphylococcus aureus serine hydrolases?

Conclusion

The study successfully identified selective inhibitors for three serine hydrolases in Staphylococcus aureus, which could be potential therapeutic targets.

Supporting Evidence

  • Selective inhibitors of FphH impaired bacterial growth and biofilm formation.
  • High-throughput screening identified 371 active hits across three enzymes.
  • X-ray crystallography validated the binding mode of several inhibitors.

Takeaway

Researchers found special medicines that can stop bad bacteria from growing and forming protective layers, which helps in treating infections.

Methodology

The study used a high-throughput screening of a library of 1,600 covalent electrophiles against three serine hydrolases in Staphylococcus aureus.

Limitations

The study may not account for all potential interactions and effects in a living organism.

Digital Object Identifier (DOI)

10.21203/rs.3.rs-5494070

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