Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence

Nature Communications
Pauline Yoong, Victor J Torres

Abstract

Staphylococcus aureus subverts host defences by producing a collection of virulence factors including bi-component pore-forming leukotoxins. Despite extensive sequence conservation, each leukotoxin has unique properties, including disparate cellular receptors and species specificities. How these toxins collectively influence S. aureus pathogenesis is unknown. Here we demonstrate that the leukotoxins LukSF-PV and LukED antagonize each other's cytolytic activities on leukocytes and erythrocytes by forming inactive hybrid complexes. Remarkably, LukSF-PV inhibition of LukED haemolytic activity on both human and murine erythrocytes prevents the release of nutrients required for in vitro bacterial growth. Using in vivo murine models of infection, we show that LukSF-PV negatively influences S. aureus virulence and colonization by inhibiting LukED. Thus, while S. aureus leukotoxins can certainly injure immune cells, the discovery of leukotoxin antagonism suggests that they may also play a role in reducing S. aureus virulence and maintaining infection without killing the host.

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Citations

Sep 18, 2016·The Journal of Infectious Diseases·David M Bamberger
Apr 20, 2017·Nature Reviews. Microbiology·András N SpaanVictor J Torres
Sep 28, 2018·PloS One·Mohamed A AbouelkhairStephen A Kania
Dec 19, 2018·The Biochemical Journal·Nikolina TrstenjakAdriana Badarau
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Jul 29, 2020·Infection and Immunity·Mohini BhattacharyaDaniel J Wozniak
May 1, 2020·Frontiers in Microbiology·Angelino T Tromp, Jos A G van Strijp
Apr 5, 2020·International Journal of Molecular Sciences·Marialaura MarchettiLuca Ronda
Jun 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Mohini BhattacharyaDaniel J Wozniak
Oct 15, 2020·The Journal of Biological Chemistry·Marilyn T VasquezVictor J Torres
Jan 18, 2021·The Journal of Biological Chemistry·Marilyn T VasquezVictor J Torres

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Methods Mentioned

BETA
flow cytometry
PCR
restriction digests
Assay

Software Mentioned

LukED
Prism
FACSDiva
GraphPad

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