Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer's patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut-eye axis.

• Klíčová slova
• Escherichia coli Nissle 1917, experimental autoimmune uveitis, macrophages, mucosal immune system, probiotics,
• MeSH
• autoimunitní nemoci terapie   MeSH
• Escherichia coli * MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• probiotika * aplikace a dávkování   farmakologie   MeSH
• střevní sliznice patologie   MeSH
• uveitida terapie   MeSH
• zánět terapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This review summarizes the main results obtained in the fields of general and molecular microbiology and microbial genetics at the Institute of Microbiology of the Academy of Sciences of the Czech Republic (AS CR) [formerly Czechoslovak Academy of Sciences (CAS)] over more than 50 years. Contribution of the founder of the Institute, academician Ivan Málek, to the introduction of these topics into the scientific program of the Institute of Microbiology and to further development of these studies is also included.

• MeSH
• akademie a ústavy dějiny   MeSH
• dějiny 20. století MeSH
• mikrobiální genetika dějiny   MeSH
• molekulární biologie dějiny   MeSH
• Check Tag
• dějiny 20. století MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Type I restriction-modification (R-M) systems are the most complex restriction enzymes discovered to date. Recent years have witnessed a renaissance of interest in R-M enzymes Type I. The massive ongoing sequencing programmes leading to discovery of, so far, more than 1 000 putative enzymes in a broad range of microorganisms including pathogenic bacteria, revealed that these enzymes are widely represented in nature. The aim of this study was characterisation of a putative R-M system EcoA0ORF42P identified in the commensal Escherichia coli A0 34/86 (O83: K24: H31) strain, which is efficiently used at Czech paediatric clinics for prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants. RESULTS: We have characterised a restriction-modification system EcoA0ORF42P of the commensal Escherichia coli strain A0 34/86 (O83: K24: H31). This system, designated as EcoAO83I, is a new functional member of the Type IB family, whose specificity differs from those of known Type IB enzymes, as was demonstrated by an immunological cross-reactivity and a complementation assay. Using the plasmid transformation method and the RM search computer program, we identified the DNA recognition sequence of the EcoAO83I as GGA(8N)ATGC. In consistence with the amino acids alignment data, the 3' TRD component of the recognition sequence is identical to the sequence recognized by the EcoEI enzyme. The A-T (modified adenine) distance is identical to that in the EcoAI and EcoEI recognition sites, which also indicates that this system is a Type IB member. Interestingly, the recognition sequence we determined here is identical to the previously reported prototype sequence for Eco377I and its isoschizomers. CONCLUSION: Putative restriction-modification system EcoA0ORF42P in the commensal Escherichia coli strain A0 34/86 (O83: K24: H31) was found to be a member of the Type IB family and was designated as EcoAO83I. Combination of the classical biochemical and bacterial genetics approaches with comparative genomics might contribute effectively to further classification of many other putative Type-I enzymes, especially in clinical samples.

• MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• DNA restrikčně-modifikační enzymy genetika   metabolismus   MeSH
• Escherichia coli enzymologie   genetika   MeSH
• genomika MeSH
• proteiny z Escherichia coli genetika   metabolismus   MeSH
• protilátky bakteriální metabolismus   MeSH
• restrikční endonukleasy typu I genetika   metabolismus   MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie nukleových kyselin MeSH
• sekvenční seřazení MeSH
• testy genetické komplementace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• DNA restrikčně-modifikační enzymy MeSH
• HsdM protein, Bacteria MeSH Prohlížeč
• HsdR protein, E coli MeSH Prohlížeč
• proteiny z Escherichia coli MeSH
• protilátky bakteriální MeSH
• restrikční endonukleasy typu I MeSH