Princeton University Library Catalog

Biosynthesis of AIP in the Staphylococcus aureus agr System: Re-evaluating the Role of Type I Signal Peptidase SpsB

Author/​Artist:
Wang, Xinhui Connie [Browse]
Format:
Senior thesis
Language:
English
Advisor(s):
Muir, Tom [Browse]
Department:
Princeton University. Department of Chemistry [Browse]
Class year:
2014
Description:
104 pages
Summary note:
Staphylococcus aureus, a gram-positive bacterium, is a versatile pathogen capable of causing a variety of human infections due in part to its extensive repertoire of virulence factors. One pathway involved in regulating the production of virulence factors in S. aureus is the agr system, a quorum sensing system that has received much research attention due to this link to bacterial virulence and its potential as a target for novel anti-infective therapies. Activation of signaling in this pathway depends upon a small cyclic peptide autoinducer called AIP. The goal of this study was to further evaluate the role of the type I signal peptidase SpsB, and the possible role of its inactive homologue SpsA, in catalyzing the last cleavage step of AIP biosynthesis. This was accomplished through an in vitro proteoliposome reconstitution system using precursors of two groups of AIP: AIP-I and AIP-II. The results of this study confirmed that SpsB is able to cleave the endogenous AIP-I precursor, but failed to detect AIP-II production from cleavage of the Group II precursor or a plausible role for SpsA involvement. While the results of this study added to the current body of evidence in support of SpsB’s role in the biosynthesis of AIP-I, the lack of activity in Group II, however, raises the possibility that SpsB may not be the protein that is responsible for this biosynthetic step across all AIP groups.