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

Vinetz, Joseph Michael; Ricaldi, Jessica N.; Winzeler, Elizabeth A.; Lehmann, Jason S.; Matthias, Michael A.; Corey, Victoria C.

dc.contributor.author	Lehmann, Jason S.
dc.contributor.author	Corey, Victoria C.
dc.contributor.author	Ricaldi, Jessica N.
dc.contributor.author	Vinetz, Joseph Michael
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.ispartofseries	American Journal of Tropical Medicine and Hygiene (ASTMH Journal)
dc.rights	info:eu-repo/semantics/restrictedAccess
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
dc.relation.issn	1476-1645