Natural and Synthetic Sortase A Substrates Are Processed by Via Different Pathways

Overview

Journal Bioconjug Chem

Publisher American Chemical Society

Specialty Biochemistry

Date 2022 Mar 23

PMID 35319881

Authors

Silvie Hansenova Manaskova

Kamran Nazmi

Wim Vant Hof

Alex van Belkum

Wendy E Kaman

Nathaniel I Martin

Enno C I Veerman

Floris J Bikker

Affiliations

Soon will be listed here.

Abstract

Endogenous sortase A (SrtA) covalently incorporates cell wall anchored proteins equipped with a SrtA recognition motif (LPXTG) via a lipid II-dependent pathway into the staphylococcal peptidoglycan layer. Previously, we found that the endogenous SrtA is able to recognize and process a variety of exogenously added synthetic SrtA substrates, including K(FITC)LPMTG-amide and K(FITC)-K-vancomycin-LPMTG-amide. These synthetic substrates are covalently incorporated into the bacterial peptidoglycan (PG) of with varying efficiencies. In this study, we examined if native and synthetic substrates are processed by SrtA via the same pathway. Therefore, the effect of the lipid II inhibiting antibiotic bacitracin on the incorporation of native and synthetic SrtA substrates was assessed. Treatment of with bacitracin resulted in a decreased incorporation of protein A in the bacterial cell wall, whereas incorporation of exogenous synthetic substrates was increased. These results suggest that natural and exogenous synthetic substrates are processed by via different pathways.

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