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Daniel Otzen

Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus

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Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus. / Baldry, Mara; Bojer, Martin S; Najarzadeh, Zahra et al.

In: Frontiers in Microbiology, Vol. 11, 573253, 11.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearch

Harvard

Baldry, M, Bojer, MS, Najarzadeh, Z, Vestergaard, M, Meyer, RL, Otzen, DE & Ingmer, H 2020, 'Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus', Frontiers in Microbiology, vol. 11, 573253. https://doi.org/10.3389/fmicb.2020.573253

APA

Baldry, M., Bojer, M. S., Najarzadeh, Z., Vestergaard, M., Meyer, R. L., Otzen, D. E., & Ingmer, H. (2020). Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus. Frontiers in Microbiology, 11, [573253]. https://doi.org/10.3389/fmicb.2020.573253

CBE

Baldry M, Bojer MS, Najarzadeh Z, Vestergaard M, Meyer RL, Otzen DE, Ingmer H. 2020. Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus. Frontiers in Microbiology. 11:Article 573253. https://doi.org/10.3389/fmicb.2020.573253

MLA

Vancouver

Baldry M, Bojer MS, Najarzadeh Z, Vestergaard M, Meyer RL, Otzen DE et al. Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus. Frontiers in Microbiology. 2020 Nov;11:573253. doi: 10.3389/fmicb.2020.573253

Author

Baldry, Mara ; Bojer, Martin S ; Najarzadeh, Zahra et al. / Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus. In: Frontiers in Microbiology. 2020 ; Vol. 11.

Bibtex

@article{8fd35108006e488c94e0f751f050ac74,
title = "Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus",
abstract = "Staphylococcus aureus is a human pathogen that can cause chronic and recurrent infections and is recalcitrant to antibiotic chemotherapy. This trait is partly attributed to its ability to form persister cells, which are subpopulations of cells that are tolerant to lethal concentrations of antibiotics. Recently, we showed that the phenol-soluble modulins (PSMs) expressed by S. aureus reduce persister cell formation. PSMs are a versatile group of toxins that, in addition to toxicity, form amyloid-like fibrils thought to support biofilm structures. Here, we examined individual or combined synthetic PSMα peptides and their equivalent amyloid-like fibrils on ciprofloxacin-selected S. aureus persister cells. We found that PSMα2 and the mixture of all four alpha peptides consistently were able to reduce persister frequency in all growth phases, and this activity was specifically linked to the presence of the soluble peptide as no effect was seen with fibrillated peptides. Persister reduction was particularly striking in a mutant that, due to mutations in the Krebs cycle, has enhanced ability to form persisters with PSMα4 and the combination of peptides being most effective. In biofilms, only the combination of peptides displayed persister reducing activity. Collectively, we report the individual contributions of PSMα peptides to persister cell reduction and that the combination of peptides generally was most effective. Strikingly, the fibrillated peptides lost activity and thus, if formed in bacterial cultures, they will be inactive against persister cells. Further studies will be needed to address the biological role of phenol-soluble modulins in reducing persister cells.",
author = "Mara Baldry and Bojer, {Martin S} and Zahra Najarzadeh and Martin Vestergaard and Meyer, {Rikke Louise} and Otzen, {Daniel Erik} and Hanne Ingmer",
note = "Copyright {\textcopyright} 2020 Baldry, Bojer, Najarzadeh, Vestergaard, Meyer, Otzen and Ingmer.",
year = "2020",
month = nov,
doi = "10.3389/fmicb.2020.573253",
language = "English",
volume = "11",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S.A",

}

RIS

TY - JOUR

T1 - Phenol-Soluble Modulins Modulate Persister Cell Formation in Staphylococcus aureus

AU - Baldry, Mara

AU - Bojer, Martin S

AU - Najarzadeh, Zahra

AU - Vestergaard, Martin

AU - Meyer, Rikke Louise

AU - Otzen, Daniel Erik

AU - Ingmer, Hanne

N1 - Copyright © 2020 Baldry, Bojer, Najarzadeh, Vestergaard, Meyer, Otzen and Ingmer.

PY - 2020/11

Y1 - 2020/11

N2 - Staphylococcus aureus is a human pathogen that can cause chronic and recurrent infections and is recalcitrant to antibiotic chemotherapy. This trait is partly attributed to its ability to form persister cells, which are subpopulations of cells that are tolerant to lethal concentrations of antibiotics. Recently, we showed that the phenol-soluble modulins (PSMs) expressed by S. aureus reduce persister cell formation. PSMs are a versatile group of toxins that, in addition to toxicity, form amyloid-like fibrils thought to support biofilm structures. Here, we examined individual or combined synthetic PSMα peptides and their equivalent amyloid-like fibrils on ciprofloxacin-selected S. aureus persister cells. We found that PSMα2 and the mixture of all four alpha peptides consistently were able to reduce persister frequency in all growth phases, and this activity was specifically linked to the presence of the soluble peptide as no effect was seen with fibrillated peptides. Persister reduction was particularly striking in a mutant that, due to mutations in the Krebs cycle, has enhanced ability to form persisters with PSMα4 and the combination of peptides being most effective. In biofilms, only the combination of peptides displayed persister reducing activity. Collectively, we report the individual contributions of PSMα peptides to persister cell reduction and that the combination of peptides generally was most effective. Strikingly, the fibrillated peptides lost activity and thus, if formed in bacterial cultures, they will be inactive against persister cells. Further studies will be needed to address the biological role of phenol-soluble modulins in reducing persister cells.

AB - Staphylococcus aureus is a human pathogen that can cause chronic and recurrent infections and is recalcitrant to antibiotic chemotherapy. This trait is partly attributed to its ability to form persister cells, which are subpopulations of cells that are tolerant to lethal concentrations of antibiotics. Recently, we showed that the phenol-soluble modulins (PSMs) expressed by S. aureus reduce persister cell formation. PSMs are a versatile group of toxins that, in addition to toxicity, form amyloid-like fibrils thought to support biofilm structures. Here, we examined individual or combined synthetic PSMα peptides and their equivalent amyloid-like fibrils on ciprofloxacin-selected S. aureus persister cells. We found that PSMα2 and the mixture of all four alpha peptides consistently were able to reduce persister frequency in all growth phases, and this activity was specifically linked to the presence of the soluble peptide as no effect was seen with fibrillated peptides. Persister reduction was particularly striking in a mutant that, due to mutations in the Krebs cycle, has enhanced ability to form persisters with PSMα4 and the combination of peptides being most effective. In biofilms, only the combination of peptides displayed persister reducing activity. Collectively, we report the individual contributions of PSMα peptides to persister cell reduction and that the combination of peptides generally was most effective. Strikingly, the fibrillated peptides lost activity and thus, if formed in bacterial cultures, they will be inactive against persister cells. Further studies will be needed to address the biological role of phenol-soluble modulins in reducing persister cells.

U2 - 10.3389/fmicb.2020.573253

DO - 10.3389/fmicb.2020.573253

M3 - Journal article

C2 - 33240231

VL - 11

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

M1 - 573253

ER -