Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides.
Adenosine Triphosphatases
/ antagonists & inhibitors
Antimicrobial Cationic Peptides
/ immunology
Bacterial Proteins
/ antagonists & inhibitors
Drug Resistance, Bacterial
/ drug effects
Drug Therapy, Combination
/ methods
Histatins
/ immunology
Humans
Immunity, Innate
Leukocytes, Mononuclear
/ immunology
Microbial Sensitivity Tests
Mutation
Neutrophils
/ immunology
Phagocytosis
/ drug effects
Polymyxins
/ pharmacology
Resveratrol
/ pharmacology
Staphylococcal Infections
/ drug therapy
Staphylococcus aureus
/ drug effects
beta-Defensins
/ immunology
Cathelicidins
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
received:
18
02
2020
accepted:
08
06
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Antimicrobial peptides (AMPs) are an important part of the human innate immune system for protection against bacterial infections, however the AMPs display varying degrees of activity against Staphylococcus aureus. Previously, we showed that inactivation of the ATP synthase sensitizes S. aureus towards the AMP antibiotic class of polymyxins. Here we wondered if the ATP synthase similarly is needed for tolerance towards various human AMPs, including human β-defensins (hBD1-4), LL-37 and histatin 5. Importantly, we find that the ATP synthase mutant (atpA) is more susceptible to killing by hBD4, hBD2, LL-37 and histatin 5 than wild type cells, while no changes in susceptibility was detected for hBD3 and hBD1. Administration of the ATP synthase inhibitor, resveratrol, sensitizes S. aureus towards hBD4-mediated killing. Neutrophils rely on AMPs and reactive oxygen molecules to eliminate bacteria and the atpA mutant is more susceptible to killing by neutrophils than the WT, even when the oxidative burst is inhibited.These results show that the staphylococcal ATP synthase enhance tolerance of S. aureus towards some human AMPs and this indicates that inhibition of the ATP synthase may be explored as a new therapeutic strategy that sensitizes S. aureus to naturally occurring AMPs of the innate immune system.
Identifiants
pubmed: 32647350
doi: 10.1038/s41598-020-68146-4
pii: 10.1038/s41598-020-68146-4
pmc: PMC7347559
doi:
Substances chimiques
Antimicrobial Cationic Peptides
0
Bacterial Proteins
0
HTN3 protein, human
0
Histatins
0
Polymyxins
0
beta-Defensins
0
Adenosine Triphosphatases
EC 3.6.1.-
Resveratrol
Q369O8926L
Cathelicidins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11391Références
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