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

Silvie Hansenová Maňásková; Kamran Nazmi; Wim Van't Hof; Alex Van Belkum; Wendy E. Kaman; Nathaniel I. Martin; Enno C.I. Veerman; Floris J. Bikker

doi:10.1021/acs.bioconjchem.2c00012

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

Silvie Hansenová Maňásková, Kamran Nazmi, Wim Van't Hof, Alex Van Belkum, Wendy E. Kaman^*, Nathaniel I. Martin, Enno C.I. Veerman, Floris J. Bikker

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	555-559
Number of pages	5
Journal	Bioconjugate Chemistry
Volume	33
Issue number	4
DOIs	https://doi.org/10.1021/acs.bioconjchem.2c00012
Publication status	Published - 20 Apr 2022

Bibliographical note

Funding Information:
This work was supported by ZonMW; grant title: Exploiting Staphylococcus aureus sortase for anti-infective purposes with the project number: 50-51700-98-055. The funding organization was involved in financial support for conducting the research only.

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

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title = "Natural and Synthetic Sortase A Substrates Are Processed by Staphylococcus aureus via Different Pathways",

abstract = "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.",

author = "\{Hansenov{\'a} Ma{\v n}{\'a}skov{\'a}\}, Silvie and Kamran Nazmi and \{Van't Hof\}, Wim and \{Van Belkum\}, Alex and Kaman, \{Wendy E.\} and Martin, \{Nathaniel I.\} and Veerman, \{Enno C.I.\} and Bikker, \{Floris J.\}",

note = "Funding Information: This work was supported by ZonMW; grant title: Exploiting Staphylococcus aureus sortase for anti-infective purposes with the project number: 50-51700-98-055. The funding organization was involved in financial support for conducting the research only. Publisher Copyright: {\textcopyright} 2022 American Chemical Society. All rights reserved.",

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doi = "10.1021/acs.bioconjchem.2c00012",

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AU - Hansenová Maňásková, Silvie

AU - Nazmi, Kamran

AU - Van't Hof, Wim

AU - Van Belkum, Alex

AU - Kaman, Wendy E.

AU - Martin, Nathaniel I.

AU - Veerman, Enno C.I.

AU - Bikker, Floris J.

N1 - Funding Information: This work was supported by ZonMW; grant title: Exploiting Staphylococcus aureus sortase for anti-infective purposes with the project number: 50-51700-98-055. The funding organization was involved in financial support for conducting the research only. Publisher Copyright: © 2022 American Chemical Society. All rights reserved.

PY - 2022/4/20

Y1 - 2022/4/20

N2 - 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.

AB - 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.

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DO - 10.1021/acs.bioconjchem.2c00012

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ER -

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

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