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      Comparative Genomic Analyses Reveal Core-Genome-Wide Genes Under Positive Selection and Major Regulatory Hubs in Outlier Strains of Pseudomonas aeruginosa

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          Abstract

          Genomic information for outlier strains of Pseudomonas aeruginosa is exiguous when compared with classical strains. We sequenced and constructed the complete genome of an environmental strain CR1 of P. aeruginosa and performed the comparative genomic analysis. It clustered with the outlier group, hence we scaled up the analyses to understand the differences in environmental and clinical outlier strains. We identified eight new regions of genomic plasticity and a plasmid pCR1 with a VirB/D4 complex followed by trimeric auto-transporter that can induce virulence phenotype in the genome of strain CR1. Virulence genotype analysis revealed that strain CR1 lacked hemolytic phospholipase C and D, three genes for LPS biosynthesis and had reduced antibiotic resistance genes when compared with clinical strains. Genes belonging to proteases, bacterial exporters and DNA stabilization were found to be under strong positive selection, thus facilitating pathogenicity and survival of the outliers. The outliers had the complete operon for the production of vibrioferrin, a siderophore present in plant growth promoting bacteria. The competence to acquire multidrug resistance and new virulence factors makes these strains a potential threat. However, we identified major regulatory hubs that can be used as drug targets against both the classical and outlier groups.

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          Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

          The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
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            Statistical mechanics of complex networks

            Reviews of Modern Physics, 74(1), 47-97
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              Digital DNA-DNA hybridization for microbial species delineation by means of genome-to-genome sequence comparison

              The pragmatic species concept for Bacteria and Archaea is ultimately based on DNA-DNA hybridization (DDH). While enabling the taxonomist, in principle, to obtain an estimate of the overall similarity between the genomes of two strains, this technique is tedious and error-prone and cannot be used to incrementally build up a comparative database. Recent technological progress in the area of genome sequencing calls for bioinformatics methods to replace the wet-lab DDH by in-silico genome-to-genome comparison. Here we investigate state-of-the-art methods for inferring whole-genome distances in their ability to mimic DDH. Algorithms to efficiently determine high-scoring segment pairs or maximally unique matches perform well as a basis of inferring intergenomic distances. The examined distance functions, which are able to cope with heavily reduced genomes and repetitive sequence regions, outperform previously described ones regarding the correlation with and error ratios in emulating DDH. Simulation of incompletely sequenced genomes indicates that some distance formulas are very robust against missing fractions of genomic information. Digitally derived genome-to-genome distances show a better correlation with 16S rRNA gene sequence distances than DDH values. The future perspectives of genome-informed taxonomy are discussed, and the investigated methods are made available as a web service for genome-based species delineation.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                06 February 2019
                2019
                : 10
                : 53
                Affiliations
                [1] 1Department of Zoology, University of Delhi , New Delhi, India
                [2] 2PhiXGen Private Limited , Gurugram, India
                [3] 3Department of Veterinary & Biomedical Sciences, South Dakota State University , Brookings, SD, United States
                [4] 4National Centre for Microbial Resource, National Centre for Cell Science , Pune, India
                [5] 5ICAR-Indian Institute of Soil Science , Bhopal, India
                Author notes

                Edited by: Vasco Ariston De Carvalho Azevedo, Universidade Federal de Minas Gerais, Brazil

                Reviewed by: Vasvi Chaudhry, University of Tübingen, Germany; Marcus Vinicius Canário Viana, Universidade Federal do Pará, Brazil

                *Correspondence: Rup Lal, ruplal@ 123456gmail.com Mallikarjun Shakarad, beelab.ms@ 123456gmail.com

                This article was submitted to Evolutionary and Genomic Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2019.00053
                6372532
                30787911
                be45b375-5a31-4a32-ba4a-5374b23b1ffe
                Copyright © 2019 Sood, Hira, Kumar, Bajaj, Rao, Lal and Shakarad.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 November 2018
                : 14 January 2019
                Page count
                Figures: 7, Tables: 5, Equations: 0, References: 114, Pages: 23, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                pseudomonas aeruginosa,outliers,environmental genomics,drug targets,positive selection

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