Outer membrane vesicles (OMVs) are nanoscale proteoliposomes secreted from the cell envelope of all Gram-negative bacteria. Originally considered as an artifact of the cell wall, OMVs are now recognized as a general secretion system, which serves to improve the fitness of bacteria and facilitate bacterial interactions in polymicrobial communities as well as interactions between the microbe and the host. In general, OMVs are released in increased amounts from pathogenic bacteria and have been found to harbor much of the contents of the parental bacterium. They mainly encompass components of the outer membrane and the periplasm including various virulence factors such as toxins, adhesins, and immunomodulatory molecules. Numerous studies have clearly shown that the delivery of toxins and other virulence factors via OMVs essentially influences their interactions with host cells. Here, we review the OMV-mediated intracellular deployment of toxins and other virulence factors with a special focus on intestinal pathogenic Escherichia coli. Especially, OMVs ubiquitously produced and secreted by enterohemorrhagic E. coli (EHEC) appear as a highly advanced mechanism for secretion and simultaneous, coordinated and direct delivery of bacterial virulence factors into host cells. OMV-associated virulence factors are not only stabilized by the association with OMVs, but can also often target previously unknown target structures and perform novel activities. The toxins are released by OMVs in their active forms and are transported via cell sorting processes to their specific cell compartments, where they can develop their detrimental effects. OMVs can be considered as bacterial "long distance weapons" that attack host tissues and help bacterial pathogens to establish the colonization of their biological niche(s), impair host cell function, and modulate the defense of the host. Thus, OMVs contribute significantly to the virulence of the pathogenic bacteria.
- MeSH
- bakteriální sekreční systémy metabolismus MeSH
- bakteriální toxiny metabolismus MeSH
- enterohemoragická Escherichia coli metabolismus patogenita MeSH
- enterotoxigenní Escherichia coli metabolismus patogenita MeSH
- enterotoxiny metabolismus MeSH
- faktory virulence metabolismus MeSH
- fyziologický stres MeSH
- infekce vyvolané Escherichia coli mikrobiologie MeSH
- lidé MeSH
- proteolipidy metabolismus ultrastruktura MeSH
- střeva mikrobiologie MeSH
- transport proteinů MeSH
- virulence MeSH
- vnější bakteriální membrána metabolismus ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Biogenesis of F1Fo ATP synthase, the key enzyme of mitochondrial energy provision, depends on transmembrane protein 70 (TMEM70), localized in the inner mitochondrial membrane of higher eukaryotes. TMEM70 absence causes severe ATP-synthase deficiency and leads to a neonatal mitochondrial encephalocardiomyopathy in humans. However, the exact biochemical function of TMEM70 remains unknown. Using TMEM70 conditional knockout in mice, we show that absence of TMEM70 impairs the early stage of enzyme biogenesis by preventing incorporation of hydrophobic subunit c into rotor structure of the enzyme. This results in the formation of an incomplete, pathologic enzyme complex consisting of F1 domain and peripheral stalk but lacking Fo proton channel composed of subunits c and a. We demonstrated direct interaction between TMEM70 and subunit c and showed that overexpression of subunit c in TMEM70-/- cells partially rescued TMEM70 defect. Accordingly, TMEM70 knockdown prevented subunit c accumulation otherwise observed in F1-deficient cells. Altogether, we identified TMEM70 as specific ancillary factor for subunit c. The biologic role of TMEM70 is to increase the low efficacy of spontaneous assembly of subunit c oligomer, the key and rate-limiting step of ATP-synthase biogenesis, and thus to reach an adequately high physiologic level of ATP synthase in mammalian tissues.-Kovalčíková, J., Vrbacký, M., Pecina, P., Tauchmannová, K., Nůsková, H., Kaplanová, V., Brázdová, A., Alán, L., Eliáš, J., Čunátová, K., Kořínek, V., Sedlacek, R., Mráček, T., Houštěk, J. TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme.
- MeSH
- genotyp MeSH
- genový knockout metody MeSH
- HEK293 buňky MeSH
- kultivované buňky MeSH
- lidé MeSH
- mitochondriální proteiny genetika metabolismus MeSH
- mitochondriální protonové ATPasy genetika metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- proteolipidy metabolismus MeSH
- regulace genové exprese MeSH
- tamoxifen farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- adenosintrifosfát metabolismus MeSH
- butyráty metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- lipidové dvojvrstvy metabolismus MeSH
- membránové proteiny fyziologie chemie metabolismus MeSH
- proteolipidy metabolismus MeSH
- protony MeSH
- transportní proteiny fyziologie chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- MeSH
- adenokarcinom klasifikace metabolismus sekundární MeSH
- homeodoménové proteiny metabolismus MeSH
- jaderné proteiny metabolismus MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory plic klasifikace metabolismus patologie MeSH
- proteolipidy metabolismus MeSH
- transkripční faktory metabolismus MeSH
- Check Tag
- lidé MeSH
- MeSH
- biologický transport MeSH
- cyklické N-oxidy analýza MeSH
- křečci praví MeSH
- mastné kyseliny metabolismus MeSH
- membránové proteiny chemie metabolismus MeSH
- mitochondrie metabolismus MeSH
- proteolipidy metabolismus MeSH
- transportní proteiny chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- zvířata MeSH