The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions. / Baldry, Mara; Kitir, Betül; Frøkiær, Hanne; Christensen, Simon B.; Taverne, Nico; Meijerink, Marjolein; Franzyk, Henrik; Olsen, Christian Adam; Wells, Jerry M.; Ingmer, Hanne.

In: P L o S One, Vol. 11, No. 1, e0145618, 2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Baldry, M, Kitir, B, Frøkiær, H, Christensen, SB, Taverne, N, Meijerink, M, Franzyk, H, Olsen, CA, Wells, JM & Ingmer, H 2016, 'The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions' P L o S One, vol. 11, no. 1, e0145618. https://doi.org/10.1371/journal.pone.0145618

APA

Baldry, M., Kitir, B., Frøkiær, H., Christensen, S. B., Taverne, N., Meijerink, M., ... Ingmer, H. (2016). The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions. P L o S One, 11(1), [e0145618]. https://doi.org/10.1371/journal.pone.0145618

Vancouver

Baldry M, Kitir B, Frøkiær H, Christensen SB, Taverne N, Meijerink M et al. The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions. P L o S One. 2016;11(1). e0145618. https://doi.org/10.1371/journal.pone.0145618

Author

Baldry, Mara ; Kitir, Betül ; Frøkiær, Hanne ; Christensen, Simon B. ; Taverne, Nico ; Meijerink, Marjolein ; Franzyk, Henrik ; Olsen, Christian Adam ; Wells, Jerry M. ; Ingmer, Hanne. / The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions. In: P L o S One. 2016 ; Vol. 11, No. 1.

Bibtex

@article{b7ce00f349c8489e80ec7b8557ca855c,
title = "The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions",
abstract = "Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization.",
author = "Mara Baldry and Bet{\"u}l Kitir and Hanne Fr{\o}ki{\ae}r and Christensen, {Simon B.} and Nico Taverne and Marjolein Meijerink and Henrik Franzyk and Olsen, {Christian Adam} and Wells, {Jerry M.} and Hanne Ingmer",
year = "2016",
doi = "10.1371/journal.pone.0145618",
language = "English",
volume = "11",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

RIS

TY - JOUR

T1 - The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions

AU - Baldry, Mara

AU - Kitir, Betül

AU - Frøkiær, Hanne

AU - Christensen, Simon B.

AU - Taverne, Nico

AU - Meijerink, Marjolein

AU - Franzyk, Henrik

AU - Olsen, Christian Adam

AU - Wells, Jerry M.

AU - Ingmer, Hanne

PY - 2016

Y1 - 2016

N2 - Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization.

AB - Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization.

U2 - 10.1371/journal.pone.0145618

DO - 10.1371/journal.pone.0145618

M3 - Journal article

VL - 11

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 1

M1 - e0145618

ER -

ID: 164242672