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Regulated release of membrane vesicles from the human pathogen Group A streptococcus

[2016-11-14] Release of vesicles from the outer membrane are known to play an important role in the biology of Gram-negative bacteria. They are relevant for pathogenesis and interaction of the bacteria with their environment. Only recently was it observed that membrane vesicles (MVs) also can be released from Gram-positive bacteria which lack an outer membrane and have a thick cell wall. The composition and mechanisms which govern the MV formation in Gram-positive bacteria was still unclear. Now, a new study, published in mBio, a high impact journal of the American Society for Microbiology, shows new findings on the composition and the regulation of MVs production in the Gram-positive, human pathogen, Group A streptococcus.

TEM GAS with MVElectron microscopic picture of membrane vesicles (arrows) and Group A streptococcus (GAS) cells  Group A streptococcus (GAS) is causing more than a half million peoples’ deaths every year. The infection is dependent on virulence proteins which are released through a secretory pathway. In a new study, headed by MIMS group leaders Emmanuelle Charpentier and Sun Nyunt Wai, postdocs Ulrike Resch and James Tsatsaronis and their colleagues found that virulence associated proteins and RNAs are abundant also in membrane vesicles released from GAS.

The scientists found MVs both in the cell wall surface and in the near vicinity of the bacterial cells (figure 1). The further analyses showed that the vesicle production is regulated by a two-component regulator which is virulence-associated.

“We know that membrane vesicles are produced by bacteria to defend themselves against inflammatory responses of the host cells”, Sun Nyunt Wai explained. “The two component regulator could be a target to manipulate the defence reaction."
The research team suggests now further studies of the membrane vesicle biogenesis and effects of the vesicle borne factors, peptides and RNAs on the human cells and bacteria in the GAS environment.

“We hope that we soon can find more details about the mechanisms which is governing the regulation and how it is connected to an increase of virulence factors of GAS”, says Sun Nyunt Wai, a specialist on MVs formation and regulation.

The study was performed at The Laboratory for Molecular Infection Medicine Sweden (MIMS) and at Max Planck Institute in Infection Biology, Berlin, Germany, in collaboration with scientists at the Helmholtz Centre for Infection Research, Technical University, both in Braunschweig, Hannover Medical School, all in Germany; the University of Tartu, Estonia, and the University of Vienna, Austria.

Contact:
Emmanuelle Charpentier, professor

Director, Department of Regulation in Infection Biology
Max Planck Institute in Infection Biology, Berlin, Germany
and
UCMR Linnaeus Guest Professor, Department of Molecular Biology
and The Laboratory for Molecular Infection Medicine Sweden (MIMS)
Umeå University, Sweden
This email address is being protected from spambots. You need JavaScript enabled to view it.

Sun Nyunt Wai, professor
Department of Molecular Biology
The Laboratory for Molecular Infection Medicine Sweden (MIMS)
Umeå Centre for Microbial Research (UCMR)
Umeå University, Sweden
This email address is being protected from spambots. You need JavaScript enabled to view it.

Original publication:
Resch U, Tsatsaronis JA, Le Rhun A, Stübiger G, Rohde M, Kasvandik S, Holzmeister S, Tinnefeld P, Wai SN, Charpentier E. (2016):
A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus.
MBio. 2016 Nov 1;7(6). pii: e00207-16. doi: 10.1128/mBio.00207-16

http://mbio.asm.org/content/7/6/e00207-16.long

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