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Whole Genome Shotgun Sequencing Shows Selection on Leptospira Regulatory Proteins During in vitro Culture Attenuation

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dc.contributor.author Lehmann, Jason S.
dc.contributor.author Corey, Victoria C.
dc.contributor.author Ricaldi, Jessica N.
dc.contributor.author Vinetz, Joseph M.
dc.contributor.author Winzeler, Elizabeth A.
dc.contributor.author Matthias, Michael A.
dc.date.accessioned 2019-02-06T14:53:42Z
dc.date.available 2019-02-06T14:53:42Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5459
dc.description.abstract Leptospirosis is the most common zoonotic disease worldwide with an estimated 500,000 severe cases reported annually, and case fatality rates of 12-25%, due primarily to acute kidney and lung injuries. Despite its prevalence, the molecular mechanisms underlying leptospirosis pathogenesis remain poorly understood. To identify virulence-related genes in Leptospira interrogans, we delineated cumulative genome changes that occurred during serial in vitro passage of a highly virulent strain of L. interrogans serovar Lai into a nearly avirulent isogenic derivative. Comparison of protein coding and computationally predicted noncoding RNA (ncRNA) genes between these two polyclonal strains identified 15 nonsynonymous single nucleotide variant (nsSNV) alleles that increased in frequency and 19 that decreased, whereas no changes in allelic frequency were observed among the ncRNA genes. Some of the nsSNV alleles were in six genes shown previously to be transcriptionally upregulated during exposure to in vivo-like conditions. Five of these nsSNVs were in evolutionarily conserved positions in genes related to signal transduction and metabolism. Frequency changes of minor nsSNV alleles identified in this study likely contributed to the loss of virulence during serial in vitro culture. The identification of new virulence-associated genes should spur additional experimental inquiry into their potential role in Leptospira pathogenesis. en_US
dc.language.iso eng
dc.publisher American Society of Tropical Medicine and Hygiene
dc.relation.ispartof urn:issn:0002-9637
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Virulence en_US
dc.subject Genome, Bacterial en_US
dc.subject Alleles en_US
dc.subject Bacterial Proteins/genetics/metabolism en_US
dc.subject Bacteriological Techniques en_US
dc.subject Gene Expression Regulation, Bacterial/physiology en_US
dc.subject Leptospira/genetics/metabolism/pathogenicity en_US
dc.title Whole Genome Shotgun Sequencing Shows Selection on Leptospira Regulatory Proteins During in vitro Culture Attenuation en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.4269/ajtmh.15-0401
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06 es_PE

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