Host-derived protease promotes aggregation of Staphylococcus aureus by cleaving the surface protein SasG

2024
journal article
article
dc.abstract.enStaphylococcus aureus is one of the leading causes of hospital-acquired infections, many of which begin following attachment and accumulation on indwelling medical devices or diseased tissue. These infections are often linked to the establishment of biofilms, but another often overlooked key characteristic allowing S. aureus to establish persistent infection is the formation of planktonic aggregates. Such aggregates are physiologically similar to biofilms and protect pathogens from innate immune clearance and increase antibiotic tolerance. The cell-wall-associated protein SasG has been implicated in biofilm formation via mechanisms of intercellular aggregation but the mechanism in the context of disease is largely unknown. We have previously shown that the expression of cell-wall-anchored proteins involved in biofilm formation is controlled by the ArlRS-MgrA regulatory cascade. In this work, we demonstrate that the ArlRS two-component system controls aggregation, by repressing the expression of sasG by activation of the global regulator MgrA. We also demonstrate that SasG must be proteolytically processed by a non-staphylococcal protease to induce aggregation and that strains expressing functional full-length sasG aggregate significantly upon proteolysis by a mucosal-derived host protease found in human saliva. We used fractionation and N-terminal sequencing to demonstrate that human trypsin within saliva cleaves within the A domain of SasG to expose the B domain and induce aggregation. Finally, we demonstrated that SasG is involved in virulence during mouse lung infection. Together, our data point to SasG, its processing by host proteases, and SasG-driven aggregation as important elements of S. aureus adaptation to the host environment.pl
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologiipl
dc.contributor.authorCrosby, Heidi A.
dc.contributor.authorKeim, Klara
dc.contributor.authorKwieciński, Jakub - 103976
dc.contributor.authorLangouët-Astrié, Christophe J.
dc.contributor.authorOshima, Kaori
dc.contributor.authorLaRivière, Wells B.
dc.contributor.authorSchmidt, Eric P.
dc.contributor.authorHorswill, Alexander R.
dc.date.accessioned2024-04-24T09:38:18Z
dc.date.available2024-04-24T09:38:18Z
dc.date.issued2024pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.additionalBibliogr. Jakub Kwieciński podpisany: Jakub M. Kwieciński
dc.description.number4
dc.description.versionostateczna wersja wydawcy
dc.description.volume15
dc.identifier.articleide03483-23pl
dc.identifier.doi10.1128/mbio.03483-23pl
dc.identifier.eissn2150-7511pl
dc.identifier.issn2161-2129pl
dc.identifier.urihttps://ruj.uj.edu.pl/handle/item/331431
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.typeotwarte czasopismo
dc.subject.enStaphylococcus aureuspl
dc.subject.enMRSApl
dc.subject.enSasGpl
dc.subject.enlung infectionpl
dc.subject.enaggregationpl
dc.subtypeArticlepl
dc.titleHost-derived protease promotes aggregation of Staphylococcus aureus by cleaving the surface protein SasG
dc.title.journalmBiopl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Staphylococcus aureus is one of the leading causes of hospital-acquired infections, many of which begin following attachment and accumulation on indwelling medical devices or diseased tissue. These infections are often linked to the establishment of biofilms, but another often overlooked key characteristic allowing S. aureus to establish persistent infection is the formation of planktonic aggregates. Such aggregates are physiologically similar to biofilms and protect pathogens from innate immune clearance and increase antibiotic tolerance. The cell-wall-associated protein SasG has been implicated in biofilm formation via mechanisms of intercellular aggregation but the mechanism in the context of disease is largely unknown. We have previously shown that the expression of cell-wall-anchored proteins involved in biofilm formation is controlled by the ArlRS-MgrA regulatory cascade. In this work, we demonstrate that the ArlRS two-component system controls aggregation, by repressing the expression of sasG by activation of the global regulator MgrA. We also demonstrate that SasG must be proteolytically processed by a non-staphylococcal protease to induce aggregation and that strains expressing functional full-length sasG aggregate significantly upon proteolysis by a mucosal-derived host protease found in human saliva. We used fractionation and N-terminal sequencing to demonstrate that human trypsin within saliva cleaves within the A domain of SasG to expose the B domain and induce aggregation. Finally, we demonstrated that SasG is involved in virulence during mouse lung infection. Together, our data point to SasG, its processing by host proteases, and SasG-driven aggregation as important elements of S. aureus adaptation to the host environment.
dc.affiliationpl
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologii
dc.contributor.author
Crosby, Heidi A.
dc.contributor.author
Keim, Klara
dc.contributor.author
Kwieciński, Jakub - 103976
dc.contributor.author
Langouët-Astrié, Christophe J.
dc.contributor.author
Oshima, Kaori
dc.contributor.author
LaRivière, Wells B.
dc.contributor.author
Schmidt, Eric P.
dc.contributor.author
Horswill, Alexander R.
dc.date.accessioned
2024-04-24T09:38:18Z
dc.date.available
2024-04-24T09:38:18Z
dc.date.issuedpl
2024
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.additional
Bibliogr. Jakub Kwieciński podpisany: Jakub M. Kwieciński
dc.description.number
4
dc.description.version
ostateczna wersja wydawcy
dc.description.volume
15
dc.identifier.articleidpl
e03483-23
dc.identifier.doipl
10.1128/mbio.03483-23
dc.identifier.eissnpl
2150-7511
dc.identifier.issnpl
2161-2129
dc.identifier.uri
https://ruj.uj.edu.pl/handle/item/331431
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
otwarte czasopismo
dc.subject.enpl
Staphylococcus aureus
dc.subject.enpl
MRSA
dc.subject.enpl
SasG
dc.subject.enpl
lung infection
dc.subject.enpl
aggregation
dc.subtypepl
Article
dc.title
Host-derived protease promotes aggregation of Staphylococcus aureus by cleaving the surface protein SasG
dc.title.journalpl
mBio
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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