July 7, 2019  |  

IWTomics: testing high-resolution sequence-based ‘Omics’ data at multiple locations and scales.

With increased generation of high-resolution sequence-based ‘Omics’ data, detecting statistically significant effects at different genomic locations and scales has become key to addressing several scientific questions. IWTomics is an R/Bioconductor package (integrated in Galaxy) that, exploiting sophisticated Functional Data Analysis techniques (i.e. statistical techniques that deal with the analysis of curves), allows users to pre-process, visualize and test these data at multiple locations and scales. The package provides a friendly, flexible and complete workflow that can be employed in many genomic and epigenomic applications.IWTomics is freely available at the Bioconductor website (http://bioconductor.org/packages/IWTomics) and on the main Galaxy instance (https://usegalaxy.org/).Supplementary data are available at Bioinformatics online.

July 7, 2019  |  

Complete genome sequence of the freshwater bacterium Beggiatoa leptomitoformis strain D-401.

Here, we report the complete closed genome sequence and methylome analysis of Beggiatoa leptomitoformis strain D-401 (DSM 14945, UNIQEMU 779), which is quite different from the previously described Beggiatoa leptomitoformis neotype strain D-402T (DSM 14946, UNIQEM U 779) with regard to morphology and lithotrophic growth in the presence of thiosulfate. Copyright © 2018 Fomenkov et al.

July 7, 2019  |  

Activation of the mismatch-specific endonuclease EndoMS/NucS by the replication clamp is required for high fidelity DNA replication.

The mismatch repair (MMR) system, exemplified by the MutS/MutL proteins, is widespread in Bacteria and Eukarya. However, molecular mechanisms how numerous archaea and bacteria lacking the mutS/mutL genes maintain high replication fidelity and genome stability have remained elusive. EndoMS is a recently discovered hyperthermophilic mismatch-specific endonuclease encoded by nucS in Thermococcales. We deleted the nucS from the actinobacterium Corynebacterium glutamicum and demonstrated a drastic increase of spontaneous transition mutations in the nucS deletion strain. The observed spectra of these mutations were consistent with the enzymatic properties of EndoMS in vitro. The robust mismatch-specific endonuclease activity was detected with the purified C. glutamicum EndoMS protein but only in the presence of the ß-clamp (DnaN). Our biochemical and genetic data suggest that the frequently occurring G/T mismatch is efficiently repaired by the bacterial EndoMS-ß-clamp complex formed via a carboxy-terminal sequence motif of EndoMS proteins. Our study thus has great implications for understanding how the activity of the novel MMR system is coordinated with the replisome and provides new mechanistic insight into genetic diversity and mutational patterns in industrially and clinically (e.g. Mycobacteria) important archaeal and bacterial phyla previously thought to be devoid of the MMR system.

July 7, 2019  |  

Closed complete genome sequences of two nontypeable Haemophilus influenzae strains containing novel modA alleles from the sputum of patients with chronic obstructive pulmonary disease.

Nontypeable Haemophilus influenzae (NTHi) is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease (COPD). Here, we report the complete genome sequences of NTHi strains 10P129H1 and 84P36H1, isolated from COPD patients, which contain the phase-variable epigenetic regulators ModA15 and ModA18, respectively.

July 7, 2019  |  

Pathogenesis of Helicobacter pylori infection

In this review, we highlight progress in the last year in characterizing known virulence factors like flagella and the Cag type IV secretion system with sophisticated struc- tural and biochemical approaches to yield new insight on the assembly and functions of these critical virulence determinants. Several aspects of Helicobacter pylori physi- ology were newly explored this year and evaluated for their functions during stom- ach colonization, including a fascinating role for the essential protease HtrA in allowing access of H. pylori to the basolateral side of the gastric epithelium through cleavage of the tight junction protein E- cadherin to facilitate CagA delivery. Molecular biology tools standard in model bacteria, including regulated gene expression during animal infection and fluorescent reporter gene fusions, were newly applied to H. py- lori to explore functions for urease beyond initial colonization and establish high salt consumption as a mediator of gene expression changes. New sequencing technolo- gies enabled validation of long postulated roles for DNA methylation in regulating H. pylori gene expression. On the cell biology side, elegant work using lineage tracing in the murine model and organoid primary cell culture systems has provided new in- sights into how H. pylori manipulates gastric tissue functions, locally and at a dis- tance, to promote its survival in the stomach and induce pathologic changes. Finally, new work has bolstered the case for genomic variation as an important mechanism to generate phenotypic diversity during changing environmental conditions in the context of diet manipulation in animal infection models and during human experi- mental infection after vaccination.

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