In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure

Outer membrane vesicles carrying β-lactamase (βLOMVs) protect bacteria against β-lactam antibiotics under experimental conditions, but their protective role during a patient’s treatment leading to the therapy failure is unknown. We investigated the role of βLOMVs in amoxicillin therapy failure in a...

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Autores principales:	Martina Bielaszewska, Ondřej Daniel, Otakar Nyč, Alexander Mellmann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	group A <i>Streptococcus pyogenes</i> (GAS) pharyngotonsillitis amoxicillin therapy failure β-lactamase-carrying outer membrane vesicles <i>Haemophilus influenzae</i> in vivo secretion Chemical technology TP1-1185 Chemical engineering TP155-156
Acceso en línea:	https://doaj.org/article/dc4a1d7c62af4de88b854725a710f075
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spelling	oai:doaj.org-article:dc4a1d7c62af4de88b854725a710f0752021-11-25T18:19:29ZIn Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure10.3390/membranes111108062077-0375https://doaj.org/article/dc4a1d7c62af4de88b854725a710f0752021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0375/11/11/806https://doaj.org/toc/2077-0375Outer membrane vesicles carrying β-lactamase (βLOMVs) protect bacteria against β-lactam antibiotics under experimental conditions, but their protective role during a patient’s treatment leading to the therapy failure is unknown. We investigated the role of βLOMVs in amoxicillin therapy failure in a patient with group A <i>Streptococcus pyogenes</i> (GAS) pharyngotonsillitis. The patient’s throat culture was examined by standard microbiological procedures. Bacterial vesicles were analyzed for β-lactamase by immunoblot and the nitrocefin assay, and in vivo secretion of βLOMVs was detected by electron microscopy. These analyses demonstrated that the patient’s throat culture grew, besides amoxicillin-susceptible GAS, an amoxicillin-resistant nontypeable <i>Haemophilus influenzae</i> (NTHi), which secreted βLOMVs. Secretion and β-lactamase activity of NTHi βLOMVs were induced by amoxicillin concentrations reached in the tonsils during therapy. The presence of NTHi βLOMVs significantly increased the minimal inhibitory concentration of amoxicillin for GAS and thereby protected GAS against bactericidal concentrations of amoxicillin. NTHi βLOMVs were identified in the patient’s pharyngotonsillar swabs and saliva, demonstrating their secretion in vivo at the site of infection. We conclude that the pathogen protection via βLOMVs secreted by the flora colonizing the infection site represents a yet underestimated mechanism of β-lactam therapy failure that warrants attention in clinical studies.Martina BielaszewskaOndřej DanielOtakar NyčAlexander MellmannMDPI AGarticlegroup A <i>Streptococcus pyogenes</i> (GAS)pharyngotonsillitisamoxicillin therapy failureβ-lactamase-carrying outer membrane vesicles<i>Haemophilus influenzae</i>in vivo secretionChemical technologyTP1-1185Chemical engineeringTP155-156ENMembranes, Vol 11, Iss 806, p 806 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	group A <i>Streptococcus pyogenes</i> (GAS) pharyngotonsillitis amoxicillin therapy failure β-lactamase-carrying outer membrane vesicles <i>Haemophilus influenzae</i> in vivo secretion Chemical technology TP1-1185 Chemical engineering TP155-156
spellingShingle	group A <i>Streptococcus pyogenes</i> (GAS) pharyngotonsillitis amoxicillin therapy failure β-lactamase-carrying outer membrane vesicles <i>Haemophilus influenzae</i> in vivo secretion Chemical technology TP1-1185 Chemical engineering TP155-156 Martina Bielaszewska Ondřej Daniel Otakar Nyč Alexander Mellmann In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure
description	Outer membrane vesicles carrying β-lactamase (βLOMVs) protect bacteria against β-lactam antibiotics under experimental conditions, but their protective role during a patient’s treatment leading to the therapy failure is unknown. We investigated the role of βLOMVs in amoxicillin therapy failure in a patient with group A <i>Streptococcus pyogenes</i> (GAS) pharyngotonsillitis. The patient’s throat culture was examined by standard microbiological procedures. Bacterial vesicles were analyzed for β-lactamase by immunoblot and the nitrocefin assay, and in vivo secretion of βLOMVs was detected by electron microscopy. These analyses demonstrated that the patient’s throat culture grew, besides amoxicillin-susceptible GAS, an amoxicillin-resistant nontypeable <i>Haemophilus influenzae</i> (NTHi), which secreted βLOMVs. Secretion and β-lactamase activity of NTHi βLOMVs were induced by amoxicillin concentrations reached in the tonsils during therapy. The presence of NTHi βLOMVs significantly increased the minimal inhibitory concentration of amoxicillin for GAS and thereby protected GAS against bactericidal concentrations of amoxicillin. NTHi βLOMVs were identified in the patient’s pharyngotonsillar swabs and saliva, demonstrating their secretion in vivo at the site of infection. We conclude that the pathogen protection via βLOMVs secreted by the flora colonizing the infection site represents a yet underestimated mechanism of β-lactam therapy failure that warrants attention in clinical studies.
format	article
author	Martina Bielaszewska Ondřej Daniel Otakar Nyč Alexander Mellmann
author_facet	Martina Bielaszewska Ondřej Daniel Otakar Nyč Alexander Mellmann
author_sort	Martina Bielaszewska
title	In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure
title_short	In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure
title_full	In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure
title_fullStr	In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure
title_full_unstemmed	In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure
title_sort	in vivo secretion of β-lactamase-carrying outer membrane vesicles as a mechanism of β-lactam therapy failure
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dc4a1d7c62af4de88b854725a710f075
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In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure

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