Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec;142(12):3349-3352.e5.
doi: 10.1016/j.jid.2022.05.1092. Epub 2022 Jul 6.

The Commensal Staphylococcus warneri Makes Peptide Inhibitors of MRSA Quorum Sensing that Protect Skin from Atopic or Necrotic Damage

Morgan M Severn  1 , Young-Saeng K Cho  1 , Haider S Manzer  1 , Zoie L Bunch  2 , Ali Shahbandi  2 , Daniel A Todd  2 , Nadja B Cech  2 , Alexander R Horswill  3
Affiliations

The Commensal Staphylococcus warneri Makes Peptide Inhibitors of MRSA Quorum Sensing that Protect Skin from Atopic or Necrotic Damage

Morgan M Severn et al. J Invest Dermatol. 2022 Dec.
No abstract available

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

The authors state no conflict of interest.

Figures

Figure 1.
Figure 1.. S. warneri AIPs inhibit agr quorum sensing in opportunistic staphylococcal pathogens.
(a) The MRSA agr-I P3::YFP reporter strain was incubated with increasing doses of S. warneri cell-free CM from healthy skin or ATCC (Manassas, VA) isolates. The representative S. warneri agr-II strain is highlighted in red. Significant differences to 0% CM were calculated by ordinary one-way ANOVA followed by Dunnett’s MCT. *P < 0.05, **P < 0.01, ***P < 0.005, and ****P < 0.0001. (b) MS confirmation of S. warneri AIP-I from CM. (c) MS identification of S. warneri AIP-II from CM. (d) MRSA agr-I-IV P3::YFP reporter strains incubated with increasing concentrations of synthetic S. warneri AIP-I. (e) MRSA agr-I-IV P3::YFP reporter strains incubated with increasing concentrations of synthetic S. warneri AIP-II. (f) Calculated IC50 values for synthetic AIP inhibition of MRSA quorum sensing. The 95% confidence intervals are reported in parenthesis. (g) S. epidermidis agr-I-III P3::sGFP reporters incubated with increasing concentrations of synthetic S. warneri AIP-I. (h) S. epidermidis agr-I-III P3::sGFP reporter strains incubated with increasing concentrations of synthetic S. warneri AIP-II. (i) Calculated IC50 values for synthetic AIP inhibition of S. epidermidis quorum sensing. The 95% confidence intervals are reported in parenthesis. The 24-hour fluorescence point is shown for a, d, e, g, and h. For all experiments, error bars are mean ± SD, and results are pooled from three independent experiments. IC50 was calculated with a four-parameter logistic regression curve. agr, accessory gene regulator; AIP, autoinducing peptide; Calc., calculated; CM, conditioned media; Exp., expected; IC50, half-maximal inhibitory concentration; MCT, multiple comparisons test; MRSA, methicillin-resistant Staphylococcus aureus; MS, mass-spectrometry; NS, not significant.
Figure 2.
Figure 2.. SW protects murine skin from MRSA damage.
(a) TEWL at 72 hpi with vehicle (DMSO) or 50 μg SW synthetic AIP-I (n = 10). Error bars are mean ± SD. (b) MRSA CFUs from vehicle or AIP-I treatment 72 hpi. Significant differences from MRSA alone (vehicle) were analyzed by ordinary one-way ANOVA followed by Dunnet’s MCT for TEWL or Tukey’s MCT for CFUs. ****P < 0.0001. (c) Representative images of back skin 72 hpi. (d) TWEL at 72 hpi for indicated groups (n = 15). (e) CFUs recovered from indicated groups 72 hpi (n = 15). Significant differences from MRSA alone (vehicle) were analyzed by ordinary one-way ANOVA followed by Dunnet’s MCT for TEWL or Tukey’s MCT for CFU data. ****P < 0.0001. (f) Representative images of back skin 72 hpi with indicated groups. (g) A 7-day weight change for groups administered vehicle (DMSO) or 50 μg synthetic SW AIP-II (n = 11 for vehicle, n = 10 for AIP). (h) A 7-day lesion-size change for groups administered vehicle (DMSO) or 50 μg synthetic SW AIP-II. Significant differences between groups were analyzed by multiple unpaired Student’s t-tests with FDR correction. *P < 0.05, **P < 0.005, and ***P < 0.0005. (i) Representative images at 3 dpi for indicated groups. AIP, autoinducing peptide; CFU, colony-forming unit; Comp., competition; FDR, false discovery rate; hpi, hour post infection; MCT, multiple comparisons test; MRSA, methicillin-resistant Staphylococcus aureus; ns, not significant; TEWL, transepithelial water loss; SW, Staphyloccocus warneri; UI, uninfected.
See this image and copyright information in PMC

References

    1. Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol 2018;16:143–55. - PubMed
    1. Byrd AL, Deming C, Cassidy SKB, Harrison OJ, Ng WI, Conlan S, et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci Transl Med 2017;9:eaal4651. - PMC - PubMed
    1. Cau L, Williams MR, Butcher AM, Nakatsuji T, Kavanaugh JS, Cheng JY, et al. Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis. J Allergy Clin Immunol 2021;147:955–966.e16. - PMC - PubMed
    1. Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship. Trends Microbiol 2018;26:484–97. - PubMed
    1. Gless BH, Bojer MS, Peng P, Baldry M, Ingmer H, Olsen CA. Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation. Nat Chem 2019;11:463–9. - PubMed

Publication types

Supplementary concepts