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dc.contributor.authorAhator, Stephen Dela
dc.contributor.authorWenzl, Karoline
dc.contributor.authorHegstad, Kristin
dc.contributor.authorLentz, Christian Stephan
dc.contributor.authorJohannessen, Mona Susan
dc.date.accessioned2024-09-10T08:58:57Z
dc.date.available2024-09-10T08:58:57Z
dc.date.issued2024-03-12
dc.description.abstractn the Staphylococcus aureus genome, a set of highly conserved two-component systems (TCSs) composed of histidine kinases (HKs) and their cognate response regulators (RRs) sense and respond to environmental stimuli, which drive the adaptation of the bacteria. This study investigates the complex interplay between TCSs in S. aureus USA300, a predominant methicillin-resistant S. aureus strain, revealing shared and unique virulence regulatory pathways and genetic variations mediating signal specificity within TCSs. Using TCS-related mutants from the Nebraska Transposon Mutant Library, we analyzed the effects of inactivated TCS HKs and RRs on the production of various virulence factors, in vitro infection abilities, and adhesion assays. We found that the TCSs’ influence on virulence determinants was not associated with their phylogenetic relationship, indicating divergent functional evolution. Using the co-crystallized structure of the DesK-DesR from Bacillus subtilis and the modeled structures of the four NarL TCSs in S. aureus, we identified interacting residues, revealing specificity determinants and conservation within the same TCS, even from different strain backgrounds. The interacting residues were highly conserved within strains but varied between species due to selection pressures and the coevolution of cognate pairs. This study unveils the complex interplay and divergent functional evolution of TCSs, highlighting their potential for future experimental exploration of phosphotransfer between cognate and non-cognate recombinant HK and RRs.en_US
dc.identifier.citationAhator, Wenzl, Hegstad, Lentz, Johannessen. Comprehensive virulence profiling and evolutionary analysis of specificity determinants in Staphylococcus aureus two-component systems. mSystems. 2024;9(4)en_US
dc.identifier.cristinIDFRIDAID 2266616
dc.identifier.doi10.1128/msystems.00130-24
dc.identifier.issn2379-5077
dc.identifier.urihttps://hdl.handle.net/10037/34644
dc.language.isoengen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.journalmSystems
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleComprehensive virulence profiling and evolutionary analysis of specificity determinants in Staphylococcus aureus two-component systemsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)