Natural and Synthetic Sortase A Substrates Are Processed by Staphylococcus aureus via Different Pathways

Bioconjugate Chemistry, vol. 33, pp. 555–559

Abstract

High Resolution Image Download MS PowerPoint Slide Endogenous Staphylococcus aureus 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 S. aureus 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 S. aureus 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 S. aureus 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 S. aureus via different pathways.

Authors 8

1. Silvie Hansenová Maňásková

   Academic Center for Dentistry Amsterdam · Erasmus MC Cancer Institute · University of Amsterdam

   Affiliation as printed

   Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands

   Department of Radiotherapy, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands

2. Kamran Nazmi

   Academic Center for Dentistry Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands

3. Wim van ‘t Hof

   Academic Center for Dentistry Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands

4. Alex van Belkum
   Affiliation as printed

   BaseClear, Sylviusweg 74, 2302 BH Leiden, The Netherlands

5. Wendy Esmeralda Kaman corresponding

   Academic Center for Dentistry Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands

6. Nathaniel I. Martin Aachen Biological Chemistry Group Institute of Biology Leiden

   Leiden University

   Affiliation as printed

   Biological Chemistry Group, Institute of Biology Leiden, Leiden University Sylviusweg 72, 2302 BH Leiden, The Netherlands

7. Enno C.I. Veerman

   Academic Center for Dentistry Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands

8. Floris Jacob Bikker

   Academic Center for Dentistry Amsterdam · University of Amsterdam

   Affiliation as printed

   Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, The Netherlands