Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus

Mara Baldry, Anita Nielsen, Martin S. Bojer, Yu Zhao, Cathrine Friberg, Dan Ifrah, Nina Glasser Heede, Thomas Ostenfeld Larsen, Hanne Frøkiær, Dorte Frees, Lixin Zhang, Huanqin Dai, Hanne Ingmer

    Research output: Contribution to journalJournal articleResearchpeer-review

    298 Downloads (Pure)


    Staphylococcus aureus is a serious human pathogen and antibiotic resistant, community-associated strains, such as the methicillin resistant S. aureus (MRSA) strain USA300, continue to spread. To avoid resistance, anti-virulence therapy has been proposed where toxicity is targeted rather than viability. Previously we have shown that norlichexanthone, a small non-reduced tricyclic polyketide produced by fungi and lichens, reduces expression of hla encoding α-hemolysin as well as the regulatory RNAIII of the agr quorum sensing system in S. aureus 8325-4. The aim of the present study was to further characterise the mode of action of norlichexanthone and its effect on biofilm formation. We find that norlichexanthone reduces expression of both hla and RNAIII also in strain USA300. Structurally, norlichexanthone resembles ω-hydroxyemodin that recently was shown to bind the agr two component response regulator, AgrA, which controls expression of RNAIII and the phenol soluble modulins responsible for human neutrophil killing. We show that norlichexanthone reduces S. aureus toxicity towards human neutrophils and interferes directly with AgrA binding to its DNA target. In contrast to ω-hydroxyemodin however, norlichexanthone reduces staphylococcal biofilm formation. Transcriptomic analysis revealed that genes regulated by the SaeRS two-component system are repressed by norlichexanthone when compared to untreated cells, an effect that was mitigated in strain Newman carrying a partially constitutive SaeRS system. Our data show that norlichexanthone treatment reduces expression of key virulence factors in CA-MRSA strain USA300 via AgrA binding and represses biofilm formation.
    Original languageEnglish
    Article numbere0168305
    JournalP L o S One
    Issue number12
    Number of pages16
    Publication statusPublished - 2016


    Dive into the research topics of 'Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus'. Together they form a unique fingerprint.

    Cite this