Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus

Jennifer A. E. Payne (), Julien Tailhades, Felix Ellett, Xenia Kostoulias, Alex J. Fulcher, Ting Fu, Ryan Leung, Stephanie Louch, Amy Tran, Severin A. Weber, Ralf B. Schittenhelm, Graham J. Lieschke, Chengxue Helena Qin, Daniel Irima, Anton Y. Peleg and Max J. Cryle ()
Additional contact information
Jennifer A. E. Payne: Monash University
Julien Tailhades: Monash University
Felix Ellett: Shriners Hospital for Children, and Harvard Medical School
Xenia Kostoulias: Monash University
Alex J. Fulcher: Monash University
Ting Fu: Monash University
Ryan Leung: Monash University
Stephanie Louch: Monash University
Amy Tran: Monash University
Severin A. Weber: Monash University
Ralf B. Schittenhelm: Monash University
Graham J. Lieschke: Monash University
Chengxue Helena Qin: Monash University
Daniel Irima: Shriners Hospital for Children, and Harvard Medical School
Anton Y. Peleg: Monash University
Max J. Cryle: Monash University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The pathogen Staphylococcus aureus can readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment. Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants. The compounds, which we term ‘antibiotic-chemoattractants’, consist of a formylated peptide (known to act as chemoattractant for neutrophil recruitment) that is covalently linked to the antibiotic vancomycin (known to bind to the bacterial cell wall). We use a combination of in vitro assays, cellular assays, infection-on-a-chip and in vivo mouse models to show that the compounds improve the recruitment, engulfment and killing of S. aureus by neutrophils. Furthermore, optimizing the formyl peptide sequence can enhance neutrophil activity through differential activation of formyl peptide receptors. Thus, we propose antibiotic-chemoattractants as an alternate approach for antibiotic development.

Date: 2021
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DOI: 10.1038/s41467-021-26244-5

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