Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus. / Baldry, Mara; Nielsen, Anita; Bojer, Martin S.; Zhao, Yu; Friberg, Cathrine; Ifrah, Dan; Heede, Nina Glasser; Larsen, Thomas O.; Frokiaer, Hanne; Frees, Dorte; Zhang, Lixin; Dai, Huanqin; Ingmer, Hanne.
I: PLOS ONE, Bind 11, Nr. 12, e0168305, 22.12.2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus
AU - Baldry, Mara
AU - Nielsen, Anita
AU - Bojer, Martin S.
AU - Zhao, Yu
AU - Friberg, Cathrine
AU - Ifrah, Dan
AU - Heede, Nina Glasser
AU - Larsen, Thomas O.
AU - Frokiaer, Hanne
AU - Frees, Dorte
AU - Zhang, Lixin
AU - Dai, Huanqin
AU - Ingmer, Hanne
PY - 2016/12/22
Y1 - 2016/12/22
N2 - 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
AB - 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
U2 - 10.1371/journal.pone.0168305
DO - 10.1371/journal.pone.0168305
M3 - Journal article
C2 - 28005941
VL - 11
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 12
M1 - e0168305
ER -
ID: 173589130