TY - JOUR
T1 - Characterization of protective extracellular membrane-derived vesicles produced by Streptococcus pneumoniae
AU - Olaya-Abril, Alfonso
AU - Prados-Rosales, Rafael
AU - McConnell, Michael J.
AU - Martín-Peña, Reyes
AU - González-Reyes, José Antonio
AU - Jiménez-Munguía, Irene
AU - Gómez-Gascón, Lidia
AU - Fernández, Javier
AU - Luque-García, José L.
AU - García-Lidón, Carlos
AU - Estévez, Héctor
AU - Pachón, Jerónimo
AU - Obando, Ignacio
AU - Casadevall, Arturo
AU - Pirofski, Liise anne
AU - Rodríguez-Ortega, Manuel J.
N1 - Funding Information:
MALDI-TOF/TOF mass spectrometry analysis was performed at the Proteomics Facility, SCAI, University of Córdoba, which is Node 6 of ProteoRed, ISCIII. This research was funded by Project Grants SAF2008-00733 ( Spanish Ministry of Science and Innovation ), P09-CTS-4616 from Consejería de Innovación, Ciencia y Empresa (Junta de Andalucía), PI-0207-2010 from Consejería de Salud (Junta de Andalucía) and FIS-P12/01259 ( Spanish Ministry of Economy and Competitiveness ) to MJRO, and by FEDER funds from the EU. AOA and LGG are both recipients of Ph.D. fellowships of the FPU Program (Spanish Ministry of Education). IJM is recipient of a Ph.D. fellowship of the PIF Program from Junta de Andalucía.
PY - 2014/6/25
Y1 - 2014/6/25
N2 - Extracellular vesicles are produced by many pathogenic microorganisms and have varied functions that include secretion and release of microbial factors, which contribute to virulence. Very little is known about vesicle production by Gram-positive bacteria, as well as their biogenesis and release mechanisms. In this work, we demonstrate the active production of vesicles by Streptococcus pneumoniae from the plasma membrane, rather than being a product from cell lysis. We biochemically characterized them by proteomics and fatty acid analysis, showing that these vesicles and the plasma membrane resemble in essential aspects, but have some differences: vesicles are more enriched in lipoproteins and short-chain fatty acids. We also demonstrate that these vesicles act as carriers of surface proteins and virulence factors. They are also highly immunoreactive against human sera and induce immune responses that protect against infection. Overall, this work provides insights into the biology of this important Gram-positive human pathogen and the role of extracellular vesicles in clinical applications. Biological significance: Pneumococcus is one of the leading causes of bacterial pneumonia worldwide in children and the elderly, being responsible for high morbidity and mortality rates in developing countries. The augment of pneumococcal disease in developed countries has raised major public health concern, since the difficulties to treat these infections due to increasing antibiotic resistance. Vaccination is still the best way to combat pneumococcal infections. One of the mechanisms that bacterial pathogens use to combat the defense responses of invaded hosts is the production and release of extracellular vesicles derived from the outer surface. Little is known about this phenomenon in Gram-positives. We show that pneumococcus produces membrane-derived vesicles particularly enriched in lipoproteins. We also show the utility of pneumococcal vesicles as a new type of vaccine, as they induce protection in immunized mice against infection with a virulent strain. This work will contribute to understand the role of these structures in important biological processes such as host-pathogen interactions and prevention of human disease.
AB - Extracellular vesicles are produced by many pathogenic microorganisms and have varied functions that include secretion and release of microbial factors, which contribute to virulence. Very little is known about vesicle production by Gram-positive bacteria, as well as their biogenesis and release mechanisms. In this work, we demonstrate the active production of vesicles by Streptococcus pneumoniae from the plasma membrane, rather than being a product from cell lysis. We biochemically characterized them by proteomics and fatty acid analysis, showing that these vesicles and the plasma membrane resemble in essential aspects, but have some differences: vesicles are more enriched in lipoproteins and short-chain fatty acids. We also demonstrate that these vesicles act as carriers of surface proteins and virulence factors. They are also highly immunoreactive against human sera and induce immune responses that protect against infection. Overall, this work provides insights into the biology of this important Gram-positive human pathogen and the role of extracellular vesicles in clinical applications. Biological significance: Pneumococcus is one of the leading causes of bacterial pneumonia worldwide in children and the elderly, being responsible for high morbidity and mortality rates in developing countries. The augment of pneumococcal disease in developed countries has raised major public health concern, since the difficulties to treat these infections due to increasing antibiotic resistance. Vaccination is still the best way to combat pneumococcal infections. One of the mechanisms that bacterial pathogens use to combat the defense responses of invaded hosts is the production and release of extracellular vesicles derived from the outer surface. Little is known about this phenomenon in Gram-positives. We show that pneumococcus produces membrane-derived vesicles particularly enriched in lipoproteins. We also show the utility of pneumococcal vesicles as a new type of vaccine, as they induce protection in immunized mice against infection with a virulent strain. This work will contribute to understand the role of these structures in important biological processes such as host-pathogen interactions and prevention of human disease.
KW - Extracellular vesicles
KW - Membrane vesicles
KW - Pneumococcus
KW - Proteomics
KW - Surface proteins
KW - Vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=84899887850&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2014.04.023
DO - 10.1016/j.jprot.2014.04.023
M3 - Article
C2 - 24769240
AN - SCOPUS:84899887850
SN - 1874-3919
VL - 106
SP - 46
EP - 60
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -