Alpha-toxin contributes to biofilm formation among Staphylococcus aureus wound isolates

Michele J. Anderson; Emily Schaaf; Laura M. Breshears; Heidi W. Wallis; James R. Johnson; Christine Tkaczyk; Bret R. Sellman; Jisun Sun; Marnie L. Peterson

doi:10.3390/toxins10040157

Alpha-toxin contributes to biofilm formation among Staphylococcus aureus wound isolates

Michele J. Anderson, Emily Schaaf, Laura M. Breshears, Heidi W. Wallis, James R. Johnson, Christine Tkaczyk, Bret R. Sellman, Jisun Sun, Marnie L. Peterson

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

16 Scopus citations

Abstract

Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production. We also investigated the effect of an anti-AT monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin-resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm defect of hla mutant SA strains. The predominant PFGE/ST combinations were USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, n = 18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, n = 20). Ex vivo AT production correlated significantly with ex vivo SA wound isolate biofilm formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo biofilm defect of non-AT producing SA strains. These findings provide evidence that AT plays a role in SA biofilm formation on epithelial surfaces and suggest that neutralization of AT may be useful in preventing and treating SA infections.

Original language	English (US)
Article number	157
Journal	Toxins
Volume	10
Issue number	4
DOIs	https://doi.org/10.3390/toxins10040157
State	Published - Apr 2018

Bibliographical note

Funding Information:
Acknowledgments: We thank David Boxrud, Minnesota Department of Health, for performing the PFGE analysis; Peter Davies, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, for his insights into the genotyping data analysis and review of the manuscript; and Charles Kistler and Patrick Finnegan, University of Wyoming, for their input and editorial assistance. This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.L.P.), and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (J.R.J.).

Funding Information:
We thank David Boxrud, Minnesota Department of Health, for performing the PFGE analysis; Peter Davies, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, for his insights into the genotyping data analysis and review of the manuscript; and Charles Kistler and Patrick Finnegan, University of Wyoming, for their input and editorial assistance. This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.L.P.), and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (J.R.J.).

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Bacterial toxin
Biofilm
Staphylococcus aureus
Toxin
Wound

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10.3390/toxins10040157

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923323

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title = "Alpha-toxin contributes to biofilm formation among Staphylococcus aureus wound isolates",

abstract = "Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production. We also investigated the effect of an anti-AT monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin-resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm defect of hla mutant SA strains. The predominant PFGE/ST combinations were USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, n = 18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, n = 20). Ex vivo AT production correlated significantly with ex vivo SA wound isolate biofilm formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo biofilm defect of non-AT producing SA strains. These findings provide evidence that AT plays a role in SA biofilm formation on epithelial surfaces and suggest that neutralization of AT may be useful in preventing and treating SA infections.",

keywords = "Bacterial toxin, Biofilm, Staphylococcus aureus, Toxin, Wound",

author = "Anderson, {Michele J.} and Emily Schaaf and Breshears, {Laura M.} and Wallis, {Heidi W.} and Johnson, {James R.} and Christine Tkaczyk and Sellman, {Bret R.} and Jisun Sun and Peterson, {Marnie L.}",

note = "Funding Information: Acknowledgments: We thank David Boxrud, Minnesota Department of Health, for performing the PFGE analysis; Peter Davies, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, for his insights into the genotyping data analysis and review of the manuscript; and Charles Kistler and Patrick Finnegan, University of Wyoming, for their input and editorial assistance. This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.L.P.), and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (J.R.J.). Funding Information: We thank David Boxrud, Minnesota Department of Health, for performing the PFGE analysis; Peter Davies, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, for his insights into the genotyping data analysis and review of the manuscript; and Charles Kistler and Patrick Finnegan, University of Wyoming, for their input and editorial assistance. This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.L.P.), and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (J.R.J.). Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2018",

month = apr,

doi = "10.3390/toxins10040157",

language = "English (US)",

volume = "10",

journal = "Toxins",

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AU - Anderson, Michele J.

AU - Schaaf, Emily

AU - Breshears, Laura M.

AU - Wallis, Heidi W.

AU - Johnson, James R.

AU - Tkaczyk, Christine

AU - Sellman, Bret R.

AU - Sun, Jisun

AU - Peterson, Marnie L.

N1 - Funding Information: Acknowledgments: We thank David Boxrud, Minnesota Department of Health, for performing the PFGE analysis; Peter Davies, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, for his insights into the genotyping data analysis and review of the manuscript; and Charles Kistler and Patrick Finnegan, University of Wyoming, for their input and editorial assistance. This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.L.P.), and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (J.R.J.). Funding Information: We thank David Boxrud, Minnesota Department of Health, for performing the PFGE analysis; Peter Davies, Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, for his insights into the genotyping data analysis and review of the manuscript; and Charles Kistler and Patrick Finnegan, University of Wyoming, for their input and editorial assistance. This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.L.P.), and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (J.R.J.). Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2018/4

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N2 - Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production. We also investigated the effect of an anti-AT monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin-resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm defect of hla mutant SA strains. The predominant PFGE/ST combinations were USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, n = 18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, n = 20). Ex vivo AT production correlated significantly with ex vivo SA wound isolate biofilm formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo biofilm defect of non-AT producing SA strains. These findings provide evidence that AT plays a role in SA biofilm formation on epithelial surfaces and suggest that neutralization of AT may be useful in preventing and treating SA infections.

AB - Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production. We also investigated the effect of an anti-AT monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin-resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm defect of hla mutant SA strains. The predominant PFGE/ST combinations were USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, n = 18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, n = 20). Ex vivo AT production correlated significantly with ex vivo SA wound isolate biofilm formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo biofilm defect of non-AT producing SA strains. These findings provide evidence that AT plays a role in SA biofilm formation on epithelial surfaces and suggest that neutralization of AT may be useful in preventing and treating SA infections.

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Alpha-toxin contributes to biofilm formation among Staphylococcus aureus wound isolates

Abstract

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Keywords

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