RESUMO
Defects in RNA splicing have been linked to human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that expression of the chromatin and alternative splicing regulator HP1γ is reduced in ulcerative colitis (UC). Accordingly, HP1γ gene inactivation in the mouse gut epithelium triggers IBD-like traits, including inflammation and dysbiosis. In parallel, we find that its loss of function broadly increases splicing noise, favoring the usage of cryptic splice sites at numerous genes with functions in gut biology. This results in the production of progerin, a toxic splice variant of prelamin A mRNA, responsible for the Hutchinson-Gilford Progeria Syndrome of premature aging. Splicing noise is also extensively detected in UC patients in association with inflammation, with progerin transcripts accumulating in the colon mucosa. We propose that monitoring HP1γ activity and RNA splicing precision can help in the management of IBD and, more generally, of accelerated aging.
Assuntos
Colite Ulcerativa , Progéria , Humanos , Camundongos , Animais , Homólogo 5 da Proteína Cromobox , Colite Ulcerativa/genética , Splicing de RNA/genética , Progéria/genética , Progéria/metabolismo , InflamaçãoRESUMO
The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia.
Assuntos
Genoma Bacteriano , Genômica , Genoma Bacteriano/genética , Filogenia , Plasmídeos , Serratia/genéticaRESUMO
Six isolates recovered from coffee seeds giving off a potato-like flavour were studied. Gene sequencing (rrs and rpoB) showed they belong to the genus Pantoea. By DNA-DNA hybridization, the isolates constituted a genomic species with less than 17% relatedness to 96 strains representing enterobacterial species. Multilocus sequence analysis (gyrB, rpoB, atpD and infB genes) showed the isolates to represent a discrete species of the genus Pantoea. Nutritional versatility of the novel species was poor. The novel species is proposed as Pantoea coffeiphila sp.nov. and its type strain is Ca04(T) (â=CIP 110718(T)â=DSM 28482(T)).
Assuntos
Café/microbiologia , Microbiologia de Alimentos , Pantoea/classificação , Filogenia , Paladar , Técnicas de Tipagem Bacteriana , Burundi , DNA Bacteriano/genética , Contaminação de Alimentos , Genes Bacterianos , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Hibridização de Ácido Nucleico , Pantoea/genética , Pantoea/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Shigella, the causative agent of bacillary dysentery, invades epithelial cells. Upon bacterial-cell contact, the type III bacterial effector IpaA binds to the cytoskeletal protein vinculin to promote actin reorganization required for efficient bacterial uptake. We show that the last 74 C-terminal residues of IpaA (A559) bind to human vinculin (HV) and promotes its association with actin filaments. Polymerisation experiments demonstrated that A559 was sufficient to induce HV-dependent partial capping of the barbed ends of actin filaments. These results suggest that IpaA regulates actin polymerisation/depolymerisation at sites of Shigella invasion by modulating the barbed end capping activity of vinculin.
Assuntos
Actinas/metabolismo , Antígenos de Bactérias/química , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Shigella/metabolismo , Vinculina/metabolismo , Actinas/química , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Sítios de Ligação , Biopolímeros/química , Biopolímeros/metabolismo , Humanos , Técnicas In Vitro , Cinética , Estrutura Terciária de Proteína , Coelhos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Shigella/genética , Shigella/patogenicidade , Vinculina/química , Vinculina/genéticaRESUMO
Phylogenetic relationships within the genus Pseudomonas were examined by comparing partial (about 1000 nucleotides) rpoB gene sequences. A total of 186 strains belonging to 75 species of Pseudomonas sensu stricto and related species were studied. The phylogenetic resolution of the rpoB tree was approximately three times higher than that of the rrs tree. Ribogroups published earlier correlated well with rpoB sequence clusters. The rpoB sequence database generated by this study was used for identification. A total of 89 isolates (79.5%) were identified to a named species, while 16 isolates (14.3%) corresponded to unnamed species, and 7 isolates (6.2%) had uncertain affiliation. rpoB sequencing is now being used for routine identification of Pseudomonas isolates in our laboratory.
Assuntos
RNA Polimerases Dirigidas por DNA/genética , Filogenia , Pseudomonas/classificação , Pseudomonas/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Dados de Sequência Molecular , Pseudomonas/enzimologia , Análise de Sequência de DNARESUMO
Bacteria of Shigella spp. are responsible for shigellosis in humans and use a type III secretion (TTS) system to enter epithelial cells and trigger apoptosis in macrophages. Transit of translocator and effector proteins through the TTS apparatus is activated upon contact of bacteria with host cells. Transcription of approximately 15 genes encoding effectors is regulated by the TTS apparatus activity and controlled by MxiE, an AraC family activator, and its coactivator IpgC, the chaperone of IpaB and IpaC translocators. Using a genetic screen, we identified ospD1 as a gene whose product negatively controls expression of genes regulated by secretion activity. OspD1 associates with the chaperone Spa15 and the activator MxiE and acts as an anti-activator until it is secreted. The mechanism regulating transcription in response to secretion activity involves an activator (MxiE), an anti-activator (OspD1), a co-anti-activator (Spa15), a coactivator (IpgC) and two anti-coactivators (IpaB and IpaC) whose alternative and mutually exclusive interactions are controlled by the duration of the TTS apparatus activity.
Assuntos
Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Chaperonas Moleculares/metabolismo , Shigella flexneri/metabolismo , Transcrição Gênica , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA , Humanos , Chaperonas Moleculares/genética , Mutação , Shigella flexneri/genética , Shigella flexneri/crescimento & desenvolvimento , Fatores de TranscriçãoRESUMO
'Streptococcus bovis/Streptococcus equinus' is a large bacterial complex including different species frequently isolated from infections of humans (Streptococcus gallolyticus, Streptococcus infantarius) or animals (S. bovis, S. equinus, Streptococcus alactolyticus). The separation of S. bovis into three different biotypes has been partially correlated with genetic differentiation. In addition, recent advances in bacterial phylogeny have led to the inclusion of Streptococcus macedonicus and Streptococcus waius in this complex. The aim of this study was to improve physiological differentiation between species related to the complex and to clarify their respective phylogenetic positions. In this study, physiological, genetic and phylogenetic analyses of a set of 88 streptococcal strains were performed. The diversity of strains of S. bovis biotype II was analysed, and it was confirmed that they belong to different species, either S. equinus or S. infantarius. It was demonstrated that S. gallolyticus, S. bovis biotype II.2, S. macedonicus and S. waius form a single DNA cluster separated into three different subspecies. They are delineated by different biochemical traits, limited DNA-DNA relatedness and noticeable divergence in 16S rDNA sequences. According to the current definition of species, the names S. gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. pasteurianus subsp. nov. and S. gallolyticus subsp. macedonicus subsp. nov. are proposed for these three subspecies.
Assuntos
Streptococcus bovis/classificação , Streptococcus/classificação , Animais , Técnicas de Tipagem Bacteriana , Bovinos , DNA Ribossômico/análise , Genes de RNAr , Humanos , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Infecções Estreptocócicas/microbiologia , Streptococcus/genética , Streptococcus/fisiologia , Streptococcus bovis/genética , Streptococcus bovis/fisiologiaRESUMO
It is admitted that one of the characteristics of pseudomonads is their inability to accumulate poly(3-hydroxybutyrate). In this paper, we show that poly(3-hydroxyoctanoate) synthesis is restricted to Pseudomonas rRNA homology group I, which includes both fluorescent and nonfluorescent species. However, within the genus Pseudomonas, the P. aeruginosa complex can be subdivided into two groups: the "P. aeruginosa group", which includes P. aeruginosa, P. alcaligenes, P. citronellolis, P. mendocina, produce poly(3-hydroxyoctanoate) from octanoate and the "P. oleovorans group" which includes the type strain of P. oleovorans, P. pseudoalcaligenes and two Pseudomonas sp., produce poly(3-hydroxybutyrate) during cultivation on octanoate. Strain GPo1 (ATCC 29347) formely identified as P. oleovorans and known to produce various medium-side-chain PHAs such as poly(3-hydroxyoctanoate) has been reclassified in the P. putida complex.
Assuntos
Caprilatos/metabolismo , Hidroxibutiratos/metabolismo , Poliésteres/metabolismo , Pseudomonas/classificação , RNA Ribossômico/genética , Genes Bacterianos , Pseudomonas/genética , Pseudomonas/metabolismo , Pseudomonas putida/classificação , Pseudomonas putida/metabolismo , RNA Bacteriano/química , RNA Bacteriano/genética , RNA Ribossômico/química , RNA Ribossômico/classificação , Homologia de Sequência do Ácido NucleicoRESUMO
Extensive biochemical testing and 16S rRNA and rpoB sequence analysis revealed that clinical strain CF01Ent1, initially identified as Buttiauxella agrestis by the use of Api 32 biochemical strips, is a new organism in the Enterobacteriaceae family. It produced an inducible AmpC-type beta-lactamase whose sequence shares 69 to 72% identity with those of the other AmpC-type beta-lactamases of ENTEROBACTERIACEAE: This enzyme exhibits an atypical high affinity for all beta-lactams tested.
