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Article

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

1
Centre for Epidemiology and Microbiology, National Institute of Public Health, 100 00 Prague, Czech Republic
2
Second Medical Faculty, Charles University, 150 06 Prague, Czech Republic
3
Institute of Medical Microbiology, University Hospital Motol, 150 06 Prague, Czech Republic
4
Institute for Hygiene, University Hospital Münster, 48149 Münster, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Ganesh Vilas Shelke, Stefania Raimondo and Jaewook Lee
Membranes 2021, 11(11), 806; https://doi.org/10.3390/membranes11110806
Received: 23 September 2021 / Revised: 18 October 2021 / Accepted: 18 October 2021 / Published: 23 October 2021
(This article belongs to the Special Issue Cell Membrane Vesicles)
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 Streptococcus pyogenes (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 Haemophilus influenzae (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. View Full-Text
Keywords: group A Streptococcus pyogenes (GAS); pharyngotonsillitis; amoxicillin therapy failure; β-lactamase-carrying outer membrane vesicles; Haemophilus influenzae; in vivo secretion; GAS protection group A Streptococcus pyogenes (GAS); pharyngotonsillitis; amoxicillin therapy failure; β-lactamase-carrying outer membrane vesicles; Haemophilus influenzae; in vivo secretion; GAS protection
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MDPI and ACS Style

Bielaszewska, M.; Daniel, O.; Nyč, O.; Mellmann, A. In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure. Membranes 2021, 11, 806. https://doi.org/10.3390/membranes11110806

AMA Style

Bielaszewska M, Daniel O, Nyč O, Mellmann A. In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure. Membranes. 2021; 11(11):806. https://doi.org/10.3390/membranes11110806

Chicago/Turabian Style

Bielaszewska, Martina, Ondřej Daniel, Otakar Nyč, and Alexander Mellmann. 2021. "In Vivo Secretion of β-Lactamase-Carrying Outer Membrane Vesicles as a Mechanism of β-Lactam Therapy Failure" Membranes 11, no. 11: 806. https://doi.org/10.3390/membranes11110806

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