Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide

Tamsin R. Sheen; Courtney K. Cavaco; Celia M. Ebrahimi; Marilyn L. Thoman; Sam D. Sanderson; Edward L. Morgan; Kelly S. Doran

doi:10.1016/j.vaccine.2011.10.054

Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide

Tamsin R. Sheen, Courtney K. Cavaco, Celia M. Ebrahimi, Marilyn L. Thoman, Sam D. Sanderson, Edward L. Morgan, Kelly S. Doran

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a serious health concern worldwide that requires new therapeutic approaches that extend beyond the development and use of new antibiotics. In this study, a conformationally biased, response-selective agonist of human C5a, known as EP67, was used to induce host innate immunity as a therapeutic method of reducing CA-MRSA infections. Using a murine model of dermonecrosis we show that EP67 treatment effectively limits CA-MRSA infection by promoting cytokine synthesis and neutrophil influx. In contrast, EP67 was ineffective in reducing lesion formation in C5a receptor (CD88^-/-) knockout mice, indicating that EP67 activates host innate immunity by engagement of CD88 bearing cells. These results suggest that EP67 may serve as a novel immunotherapeutic for prevention and treatment of CA-MRSA dermal infection.

Original language	English (US)
Pages (from-to)	9-13
Number of pages	5
Journal	Vaccine
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.vaccine.2011.10.054
State	Published - Dec 9 2011
Externally published	Yes

Keywords

C5a agonist
CA-MRSA
EP67
Innate immunity
PMN
Staphylococcus aureus

ASJC Scopus subject areas

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2011.10.054

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title = "Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide",

abstract = "The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a serious health concern worldwide that requires new therapeutic approaches that extend beyond the development and use of new antibiotics. In this study, a conformationally biased, response-selective agonist of human C5a, known as EP67, was used to induce host innate immunity as a therapeutic method of reducing CA-MRSA infections. Using a murine model of dermonecrosis we show that EP67 treatment effectively limits CA-MRSA infection by promoting cytokine synthesis and neutrophil influx. In contrast, EP67 was ineffective in reducing lesion formation in C5a receptor (CD88-/-) knockout mice, indicating that EP67 activates host innate immunity by engagement of CD88 bearing cells. These results suggest that EP67 may serve as a novel immunotherapeutic for prevention and treatment of CA-MRSA dermal infection.",

keywords = "C5a agonist, CA-MRSA, EP67, Innate immunity, PMN, Staphylococcus aureus",

author = "Sheen, {Tamsin R.} and Cavaco, {Courtney K.} and Ebrahimi, {Celia M.} and Thoman, {Marilyn L.} and Sanderson, {Sam D.} and Morgan, {Edward L.} and Doran, {Kelly S.}",

note = "Funding Information: We thank Victor Nizet for providing the USA300 strain and Joy Phillips for helpful discussions. Histopathologic analysis was performed at the UCSD Core Facility, director Nissi Varki. This work was supported in part by Grant R01GM095884 to J.P., R01AG02877 to M.L.T., the Presidential Research Grant from San Diego State University to E.L.M. and grants from the San Diego State Research Foundation and the California State University Program for Education and Research in Biotechnology (CSUPERB) to K.S.D.",

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doi = "10.1016/j.vaccine.2011.10.054",

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AU - Thoman, Marilyn L.

AU - Sanderson, Sam D.

AU - Morgan, Edward L.

AU - Doran, Kelly S.

N1 - Funding Information: We thank Victor Nizet for providing the USA300 strain and Joy Phillips for helpful discussions. Histopathologic analysis was performed at the UCSD Core Facility, director Nissi Varki. This work was supported in part by Grant R01GM095884 to J.P., R01AG02877 to M.L.T., the Presidential Research Grant from San Diego State University to E.L.M. and grants from the San Diego State Research Foundation and the California State University Program for Education and Research in Biotechnology (CSUPERB) to K.S.D.

PY - 2011/12/9

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N2 - The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a serious health concern worldwide that requires new therapeutic approaches that extend beyond the development and use of new antibiotics. In this study, a conformationally biased, response-selective agonist of human C5a, known as EP67, was used to induce host innate immunity as a therapeutic method of reducing CA-MRSA infections. Using a murine model of dermonecrosis we show that EP67 treatment effectively limits CA-MRSA infection by promoting cytokine synthesis and neutrophil influx. In contrast, EP67 was ineffective in reducing lesion formation in C5a receptor (CD88-/-) knockout mice, indicating that EP67 activates host innate immunity by engagement of CD88 bearing cells. These results suggest that EP67 may serve as a novel immunotherapeutic for prevention and treatment of CA-MRSA dermal infection.

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Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide

Abstract

Keywords

ASJC Scopus subject areas

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