Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides

Abstract 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. au...

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Autores principales:	Liping Liu, Christian Beck, Katrine Nøhr-Meldgaard, Andreas Peschel, Dorothee Kretschmer, Hanne Ingmer, Martin Vestergaard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ac98bb0ac47a4c7da137f7a0c2dcd82d
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spelling	oai:doaj.org-article:ac98bb0ac47a4c7da137f7a0c2dcd82d2021-12-02T15:39:40ZInhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides10.1038/s41598-020-68146-42045-2322https://doaj.org/article/ac98bb0ac47a4c7da137f7a0c2dcd82d2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68146-4https://doaj.org/toc/2045-2322Abstract 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.Liping LiuChristian BeckKatrine Nøhr-MeldgaardAndreas PeschelDorothee KretschmerHanne IngmerMartin VestergaardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liping Liu Christian Beck Katrine Nøhr-Meldgaard Andreas Peschel Dorothee Kretschmer Hanne Ingmer Martin Vestergaard Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
description	Abstract 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.
format	article
author	Liping Liu Christian Beck Katrine Nøhr-Meldgaard Andreas Peschel Dorothee Kretschmer Hanne Ingmer Martin Vestergaard
author_facet	Liping Liu Christian Beck Katrine Nøhr-Meldgaard Andreas Peschel Dorothee Kretschmer Hanne Ingmer Martin Vestergaard
author_sort	Liping Liu
title	Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
title_short	Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
title_full	Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
title_fullStr	Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
title_full_unstemmed	Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
title_sort	inhibition of the atp synthase sensitizes staphylococcus aureus towards human antimicrobial peptides
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/ac98bb0ac47a4c7da137f7a0c2dcd82d
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Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides

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