Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26244-5
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Funding
- National Institutes of Health [GM092804, EB002503]
- Shriners Hospital for Children
- American Australian Association
- Executive Committee for Research at the Massachusetts General Hospital
- Victorian Endowment for Science, Knowledge and Innovation (VESKI, Australia)
- Melbourne Boston Sister City Association
- Australian National Health and Medical Research Council Career Development Fellowship [APP1140619]
- Ideas grant from Australian National Health and Medical Research Council [APP2003325]
- Australian Research Council Centre of Excellence in Peptide and Protein Science [CE200100012]
- Australian National Health and Medical Research Council Practitioner Fellowship [APP1117940]
- Australian National Health and Medical Research Council Senior Research Fellowship [APP1044754]
- State Government of Victoria
- Australian Government
- Faculty of Pharmacy and Pharmaceutical Sciences (FPPS) Graduate Research Scholarship by Faculty of Pharmacy and Pharmaceutical Sciences, Monash University
- FPPS International Graduate Research Scholarship by Faculty of Pharmacy and Pharmaceutical Sciences, Monash University
- National Heart Foundation Future Leader Fellowship
- Australian National Health and Medical Research Council Grant [APP1187989]
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Researchers linked formylated peptides, which act as chemoattractants for neutrophils, with the antibiotic vancomycin, and found that these hybrid compounds improve the clearance of S. aureus by neutrophils.
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. Antibiotic resistance in Staphylococcus aureus is associated with reduced neutrophil recruitment. Here, Payne et al. link formylated peptides, which act as chemoattractants for neutrophils, with the antibiotic vancomycin and show that these hybrid compounds improve clearance of S. aureus by neutrophils.
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