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Bacterial Infections

Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms

Mohini Bhattacharya, Evelien T. M. Berends, Xuhui Zheng, Preston J. Hill, Rita Chan, Victor J. Torres, Daniel J. Wozniak
Nancy E. Freitag, Editor
Mohini Bhattacharya
aDepartment of Microbiology, Ohio State University, Columbus, Ohio, USA
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Evelien T. M. Berends
cDepartment of Microbiology, New York University School of Medicine, New York, New York, USA
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Xuhui Zheng
cDepartment of Microbiology, New York University School of Medicine, New York, New York, USA
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Preston J. Hill
bDepartment of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA
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Rita Chan
cDepartment of Microbiology, New York University School of Medicine, New York, New York, USA
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Victor J. Torres
cDepartment of Microbiology, New York University School of Medicine, New York, New York, USA
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Daniel J. Wozniak
aDepartment of Microbiology, Ohio State University, Columbus, Ohio, USA
bDepartment of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA
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Nancy E. Freitag
University of Illinois at Chicago
Roles: Editor
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DOI: 10.1128/IAI.00372-20
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ABSTRACT

Bacterial biofilms are linked with chronic infections and have properties distinct from those of planktonic, single-celled bacteria. The virulence mechanisms associated with Staphylococcus aureus biofilms are becoming better understood. Human neutrophils are critical for the innate immune response to S. aureus infection. Here, we describe two virulence strategies that converge to promote the ability of S. aureus biofilms to evade killing by neutrophils. Specifically, we show that while neutrophils exposed to S. aureus biofilms produce extracellular traps (NETs) and phagocytose bacteria, both mechanisms are inefficient in clearance of the biofilm biomass. This is attributed to the leukocidin LukAB, which promotes S. aureus survival during phagocytosis. We also show that the persistence of biofilm bacteria trapped in NETs is facilitated by S. aureus nuclease (Nuc)-mediated degradation of NET DNA. This study describes key aspects of the interaction between primary human neutrophils and S. aureus biofilms and provides insight into how S. aureus evades the neutrophil response to cause persistent infections.

FOOTNOTES

    • Received 16 July 2020.
    • Accepted 17 July 2020.
    • Accepted manuscript posted online 27 July 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms
Mohini Bhattacharya, Evelien T. M. Berends, Xuhui Zheng, Preston J. Hill, Rita Chan, Victor J. Torres, Daniel J. Wozniak
Infection and Immunity Sep 2020, 88 (10) e00372-20; DOI: 10.1128/IAI.00372-20

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Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms
Mohini Bhattacharya, Evelien T. M. Berends, Xuhui Zheng, Preston J. Hill, Rita Chan, Victor J. Torres, Daniel J. Wozniak
Infection and Immunity Sep 2020, 88 (10) e00372-20; DOI: 10.1128/IAI.00372-20
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KEYWORDS

NETs
S. aureus
biofilms
neutrophil
phagocytosis

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