Identification of a S. aureus virulence factor by activity-based protein profiling (ABPP)

Nature Chemical Biology
Christian S LentzMatthew Bogyo

Abstract

Serine hydrolases play diverse roles in regulating host-pathogen interactions in a number of organisms, yet few have been characterized in the human pathogen Staphylococcus aureus. Here we describe a chemical proteomic screen that identified ten previously uncharacterized S. aureus serine hydrolases that mostly lack human homologs. We termed these enzymes fluorophosphonate-binding hydrolases (FphA-J). One hydrolase, FphB, can process short fatty acid esters, exhibits increased activity in response to host cell factors, is located predominantly on the bacterial cell surface in a subset of cells, and is concentrated in the division septum. Genetic disruption of fphB confirmed that the enzyme is dispensable for bacterial growth in culture but crucial for establishing infection in distinct sites in vivo. A selective small molecule inhibitor of FphB effectively reduced infectivity in vivo, suggesting that it may be a viable therapeutic target for the treatment or management of Staphylococcus infections.

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Datasets Mentioned

BETA
PXD009210
FPR3757
CP000255.1

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
PCR
Affinity Purification

Software Mentioned

Gen5
MemBrain
GraphPad Prism
TmPred
Image Studio Lite
Signal
Phobius
GraphPad
BD CSampler
BLASTp

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