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Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides

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Standard

Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides. / Kubicek-Sutherland, Jessica Z.; Lofton, Hava; Vestergaard, Martin; Hjort, Karin ; Ingmer, Hanne; Anderson, Dan I.

I: Journal of Antimicrobial Chemotherapy, Bind 72, Nr. 1, 01.2017, s. 115-127.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Kubicek-Sutherland, JZ, Lofton, H, Vestergaard, M, Hjort, K, Ingmer, H & Anderson, DI 2017, 'Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides', Journal of Antimicrobial Chemotherapy, bind 72, nr. 1, s. 115-127. https://doi.org/10.1093/jac/dkw381

APA

Kubicek-Sutherland, J. Z., Lofton, H., Vestergaard, M., Hjort, K., Ingmer, H., & Anderson, D. I. (2017). Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides. Journal of Antimicrobial Chemotherapy, 72(1), 115-127. https://doi.org/10.1093/jac/dkw381

Vancouver

Kubicek-Sutherland JZ, Lofton H, Vestergaard M, Hjort K, Ingmer H, Anderson DI. Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides. Journal of Antimicrobial Chemotherapy. 2017 jan;72(1):115-127. https://doi.org/10.1093/jac/dkw381

Author

Kubicek-Sutherland, Jessica Z. ; Lofton, Hava ; Vestergaard, Martin ; Hjort, Karin ; Ingmer, Hanne ; Anderson, Dan I. / Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides. I: Journal of Antimicrobial Chemotherapy. 2017 ; Bind 72, Nr. 1. s. 115-127.

Bibtex

@article{c335ea7bd25d41dfafc08ab5096b0d0e,
title = "Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides",
abstract = "Background: The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the humaninnate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood.Objectives: We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance.Methods: Serial passage experimentswere conducted using steadily increasing concentrations of LL-37, PR-39 or wheat germ histones. WGS and proteomic analysis by MS were used to identify the molecular mechanism associatedwith increased tolerance of AMPs. AMP-resistant mutants were characterized by measuring in vitro fitness, AMP and antibiotic susceptibility, and virulence in a mouse model of sepsis.Results: AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribedantibiotics and human defence peptides.Conclusions: These findings suggest that therapeutic use of AMPs could select for virulent mutants with crossresistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated.",
author = "Kubicek-Sutherland, {Jessica Z.} and Hava Lofton and Martin Vestergaard and Karin Hjort and Hanne Ingmer and Anderson, {Dan I.}",
year = "2017",
month = "1",
doi = "10.1093/jac/dkw381",
language = "English",
volume = "72",
pages = "115--127",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides

AU - Kubicek-Sutherland, Jessica Z.

AU - Lofton, Hava

AU - Vestergaard, Martin

AU - Hjort, Karin

AU - Ingmer, Hanne

AU - Anderson, Dan I.

PY - 2017/1

Y1 - 2017/1

N2 - Background: The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the humaninnate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood.Objectives: We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance.Methods: Serial passage experimentswere conducted using steadily increasing concentrations of LL-37, PR-39 or wheat germ histones. WGS and proteomic analysis by MS were used to identify the molecular mechanism associatedwith increased tolerance of AMPs. AMP-resistant mutants were characterized by measuring in vitro fitness, AMP and antibiotic susceptibility, and virulence in a mouse model of sepsis.Results: AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribedantibiotics and human defence peptides.Conclusions: These findings suggest that therapeutic use of AMPs could select for virulent mutants with crossresistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated.

AB - Background: The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the humaninnate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood.Objectives: We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance.Methods: Serial passage experimentswere conducted using steadily increasing concentrations of LL-37, PR-39 or wheat germ histones. WGS and proteomic analysis by MS were used to identify the molecular mechanism associatedwith increased tolerance of AMPs. AMP-resistant mutants were characterized by measuring in vitro fitness, AMP and antibiotic susceptibility, and virulence in a mouse model of sepsis.Results: AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribedantibiotics and human defence peptides.Conclusions: These findings suggest that therapeutic use of AMPs could select for virulent mutants with crossresistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated.

U2 - 10.1093/jac/dkw381

DO - 10.1093/jac/dkw381

M3 - Journal article

C2 - 27650186

VL - 72

SP - 115

EP - 127

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 1

ER -

ID: 166158004