Abstract Using the Hiseq data of the German E. coli outbreak isolate TY2482, preliminary prophage analyses have been performed by some researchers previously. With the closed assembly of the same isolate being available, another round of analysis might help in resolving questions that remain unclear due to the incompleteness of the dataset.
Many proteins can be modified by multiple types of post-translational modifications (Mtp-proteins). Although some post-translational modifications (PTMs) have recently been found to be associated with life-threatening diseases like cancers and neurodegenerative disorders, the underlying mechanisms remain enigmatic to date. In this study, we examined the relationship of human Mtp-proteins and disease and systematically characterized features of these proteins. Our results indicated that Mtp-proteins are significantly more inclined to participate in disease than proteins carrying no known PTM sites. Mtp-proteins were found significantly enriched in protein complexes, having more protein partners and preferred to act as hubs/superhubs in protein-protein interaction (PPI) networks. They possess a distinct functional focus, such as chromatin assembly or disassembly, and reside in biased, multiple subcellular localizations. Moreover, most Mtp-proteins harbor more intrinsically disordered regions than the others. Mtp-proteins carrying PTM types biased toward locating in the ordered regions were mainly related to protein-DNA complex assembly. Examination of the energetic effects of PTMs on the stability of PPI revealed that only a small fraction of single PTM events influence the binding energy of >2 kcal/mol, whereas the binding energy can change dramatically by combinations of multiple PTM types. Our work not only expands the understanding of Mtp-proteins but also discloses the potential ability of Mtp-proteins to act as key elements in disease development.
Increasing yield is a principal goal when breeding Lentinus edodes. The detection of quantitative trait loci (QTLs) underlying yield and its related traits, precocity and the number of fruiting bodies (NFs), is important in order to breed high-yield cultivars. Using composite interval mapping (CIM), we mapped a total of 25 QTLs responsible for precocity, NFs, and yield in 2 segregating populations of L. edodes. QTLs for the 3 traits were mapped on 5 different linkage groups, contributing 5.9% to 15.4% of the phenotypic variation. Colocated QTLs were also found underlying multiple traits, implying the presence of a genic pleiotropic effect or tightly linked genes. This is, to our knowledge, the first report of the genetic dissection of precocity, NFs, and yield using QTL mapping in L. edodes. Findings of this study will facilitate marker-assisted breeding of high-yield cultivars of L. edodes.
In bacteria, small regulatory non-coding RNAs (sRNAs) are the most abundant class of posttranscriptional regulators.They are involved in diverse processes including quorum sensing, stress response, virulence and carbon metabolism.Recent developments in high-throughput techniques, such as genomic tiling arrays and RNA-Seq, have allowed efficient detection and characterization of bacterial sRNAs.However, a comprehensive repository to host sRNAs and their annotations is not available.Existing databases suffer from a limited number of bacterial species or sRNAs included.In addition, these databases do not have tools to integrate or analyse high-throughput sequencing data.Here, we have developed BSRD (http://kwanlab.bio.cuhk.edu.hk/BSRD), a comprehensive bacterial sRNAs database, as a repository for published bacterial sRNA sequences with annotations and expression profiles.BSRD contains over nine times more experimentally validated sRNAs than any other available databases.BSRD also provides combinatorial regulatory networks of transcription factors and sRNAs with their common targets.We have built and implemented in BSRD a novel RNA-Seq analysis platform, sRNADeep, to characterize sRNAs in large-scale transcriptome sequencing projects.We will update BSRD regularly.
Bacteria, archaea and fungi play crucial roles in wetland biogeochemical processes. However, little is known about their community structure, dynamics and interactions in subtropical coastal wetlands. Here, we examined communities of the three kingdoms in mangrove and mudflat sediments of a subtropical coastal wetland using Ion Torrent amplicon sequencing and co-occurrence network analysis. Bacterial, archaeal and fungal communities comprised mainly of members from the phyla Proteobacteria and Bacteroidetes, Bathyarchaeota and Euryarchaeota, and Ascomycota, respectively. Species richness and Shannon diversity were highest in bacteria, followed by archaea and were lowest in fungi. Distinct spatiotemporal patterns were observed, with bacterial and fungal communities varying, to different extent, between wet and dry seasons and between mangrove and mudflat, and archaeal community remaining relatively stable between seasons and regions. Redundancy analysis revealed temperature as the major driver of the seasonal patterns of bacterial and fungal communities but also highlighted the importance of interkingdom biotic factors in shaping the community structure of all three kingdoms. Potential ecological interactions and putative keystone taxa were identified based on co-occurrence network analysis. These findings facilitate current understanding of the microbial ecology of subtropical coastal wetlands and provide a basis for better modelling of ecological processes in this important ecosystem.
Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order Pasteurellales in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb Andrographis paniculata (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.
A large-scale Escherichia coli O104:H4 outbreak occurred in Germany from May to July 2011, causing numerous cases of hemolytic-uremic syndrome (HUS) and deaths. Genomes of ten outbreak isolates and a historical O104:H4 strain isolated in 2001 were sequenced using different new generation sequencing platforms. Phylogenetic analyses were performed using various approaches which either are not genome-wide or may be subject to errors due to poor sequence alignment. Also, detailed pathogenicity analyses on the 2001 strain were not available.We reconstructed the phylogeny of E. coli using the genome-wide and alignment-free feature frequency profile method and revealed the 2001 strain to be the closest relative to the 2011 outbreak strain among all available E. coli strains at present and confirmed findings from previous alignment-based phylogenetic studies that the HUS-causing O104:H4 strains are more closely related to typical enteroaggregative E. coli (EAEC) than to enterohemorrhagic E. coli. Detailed re-examination of pathogenicity-related virulence factors and secreted proteins showed that the 2001 strain possesses virulence factors shared between typical EAEC and the 2011 outbreak strain.Our study represents the first attempt to elucidate the whole-genome phylogeny of the 2011 German outbreak using an alignment-free method, and suggested a direct line of ancestry leading from a putative EAEC-like ancestor through the 2001 strain to the 2011 outbreak strain.
Abstract Patients with metastatic esophageal squamous cell carcinoma (ESCC) have a grave prognosis with limited life expectancy. Here, a phase II clinical trial was conducted to investigate the effect of Andrographis paniculata (AP) on the palliative care of patients with metastatic ESCC. Patients with metastatic or locally advanced ESCC deemed unfit for surgery, and who have already completed palliative chemotherapy or chemoradiotherapy or are not fit for these treatments, were recruited. These patients were prescribed AP concentrated granules for 4 months. They also received clinical and quality of life assessments for clinical response, as well as positron emission tomography–computed tomography at 3 and 6 months after AP treatment for the assessment of tumor volume. Furthermore, the change in gut microbiota composition after AP treatment was studied. From the results, among the 30 recruited patients, 10 completed the entire course of AP treatment, while 20 received partial AP treatment. Patients who completed the AP treatment achieved significantly longer overall survival periods with the maintenance of the quality of life during the survival period when compared to those who could not complete AP treatment. The treatment effect of AP also contributed to the shift of the overall structure of gut microbiota for ESCC patients towards those of healthy individuals. The significance of this study is the establishment of AP as a safe and effective palliative treatment for patients with squamous cell carcinoma of the esophagus. To the best of our knowledge, this is the first clinical trial of AP water extract in esophageal cancer patients demonstrating its new medicinal use.
Genomic islands (GIs), frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of “alien” elements which probably undergo special temporal–spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these “exotic” regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs) in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased “non-optimal” codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for “alien” regions, but also provide hints to the special evolutionary course and transcriptional regulation of GI regions.
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