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Toxins (Basel). 2018 Apr 16;10(4). pii: E157. doi: 10.3390/toxins10040157.

Alpha-Toxin Contributes to Biofilm Formation among Staphylococcus aureus Wound Isolates.

Author information

1
Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. manderson10@mmm.com.
2
Heath Care Business Group, 3M, St. Paul, MN 55144, USA. manderson10@mmm.com.
3
Department of Pediatric Infectious Diseases, Medical School, University of Minnesota, Minneapolis, MN 55455, USA. scha1123@umn.edu.
4
Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. bresh006@umn.edu.
5
Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. wang1530@umn.edu.
6
Veterans Affairs Medical Center, Minneapolis, MN 55417, USA. johns007@umn.edu.
7
Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN 55455, USA. johns007@umn.edu.
8
Department of Infectious Disease, MedImmune, Gaithersburg, MD 20878, USA. tkaczykc@medimmune.com.
9
Department of Infectious Disease, MedImmune, Gaithersburg, MD 20878, USA. sellmanb@medimmune.com.
10
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55455, USA. jisun.haan@state.mn.us.
11
Infectious Disease Laboratory, Minnesota Department of Health, St. Paul, MN 55164, USA. jisun.haan@state.mn.us.
12
Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. mpeter68@uwyo.edu.
13
School of Pharmacy, The University of Wyoming, Laramie, WY 82071, USA. mpeter68@uwyo.edu.

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:

Staphylococcus aureus; bacterial toxin; biofilm; toxin; wound

Conflict of interest statement

Michele J. Anderson, Emily Schaaf, Laura M. Breshears, Heidi W. Wallis, James R. Johnson, Jisun Sun, and Marnie L. Peterson do not have a commercial or other association that poses a conflict of interest. Christine Tkaczyk and Bret R. Sellman are employees of MedImmune, manufacturer of the monoclonal anti-AT neutralizing antibody MEDI4893* and the purified WT AT and AT H35L mutant.

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