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Antibiotics stimulate vesicles formation in in a phage-dependent and independent fashion and via different routes


Andreoni, Federica; Toyofuku, Masanori; Menzi, Carmen; Kalawong, Ratchara; Mairpady Shambat, Srikanth; François, Patrice; Zinkernagel, Annelies S; Eberl, Leo (2018). Antibiotics stimulate vesicles formation in in a phage-dependent and independent fashion and via different routes. Antimicrobial Agents and Chemotherapy, 63(2):e01439-18.

Abstract

Bacterial membrane vesicles research has so far mainly focussed on Gram-negative bacteria. Only recently Gram-positive bacteria have been demonstrated to produce and release extracellular membrane vesicles (MVs) that contribute to bacterial virulence. Although treatment of bacteria with antibiotics is a well-established trigger of bacterial MVs formation, the underlying mechanisms are poorly understood. In this study we show that antibiotics can induce MVs through different routes in the important human pathogen DNA damaging agents and antibiotics inducing the SOS response triggered vesicle formation in lysogenic strains of but not in their phage-devoid counterparts. β-lactam antibiotics flucloxacillin and ceftaroline increased vesicle formation in a prophage-independent manner by weakening the peptidoglycan layer. We present evidence that the amount of DNA associated with MVs formed by phage lysis is higher than that of MVs formed by β-lactam antibiotics-induced blebbing. The purified MVs derived from protected the bacteria from challenge with daptomycin, a membrane-targeting antibiotic, both and in whole blood. In addition, the MVs protected from killing in whole blood, indicating that antibiotic-induced MVs function as a decoy and thereby contribute to the survival of the bacterium.

Abstract

Bacterial membrane vesicles research has so far mainly focussed on Gram-negative bacteria. Only recently Gram-positive bacteria have been demonstrated to produce and release extracellular membrane vesicles (MVs) that contribute to bacterial virulence. Although treatment of bacteria with antibiotics is a well-established trigger of bacterial MVs formation, the underlying mechanisms are poorly understood. In this study we show that antibiotics can induce MVs through different routes in the important human pathogen DNA damaging agents and antibiotics inducing the SOS response triggered vesicle formation in lysogenic strains of but not in their phage-devoid counterparts. β-lactam antibiotics flucloxacillin and ceftaroline increased vesicle formation in a prophage-independent manner by weakening the peptidoglycan layer. We present evidence that the amount of DNA associated with MVs formed by phage lysis is higher than that of MVs formed by β-lactam antibiotics-induced blebbing. The purified MVs derived from protected the bacteria from challenge with daptomycin, a membrane-targeting antibiotic, both and in whole blood. In addition, the MVs protected from killing in whole blood, indicating that antibiotic-induced MVs function as a decoy and thereby contribute to the survival of the bacterium.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:3 December 2018
Deposited On:24 Jan 2019 10:06
Last Modified:10 Feb 2019 06:52
Publisher:American Society for Microbiology
ISSN:0066-4804
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1128/AAC.01439-18
PubMed ID:30509943

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