Universidad Peruana Cayetano Heredia

Pathogenomic Inference of Virulence-Associated Genes in Leptospira interrogans

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dc.contributor.author Lehmann, Jason S.
dc.contributor.author Fouts, Derrick E.
dc.contributor.author Haft, Daniel H.
dc.contributor.author Cannella, Anthony P.
dc.contributor.author Ricaldi, Jessica N.
dc.contributor.author Brinkac, Lauren
dc.contributor.author Harkins, Derek
dc.contributor.author Durkin, Scott
dc.contributor.author Sanka, Ravi
dc.contributor.author Sutton, Granger
dc.contributor.author Moreno, Angelo
dc.contributor.author Vinetz, Joseph Michael
dc.contributor.author Matthias, Michael A.
dc.date.accessioned 2022-01-04T20:31:47Z
dc.date.available 2022-01-04T20:31:47Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/10662
dc.description.abstract Leptospirosis is a globally important, neglected zoonotic infection caused by spirochetes of the genus Leptospira. Since genetic transformation remains technically limited for pathogenic Leptospira, a systems biology pathogenomic approach was used to infer leptospiral virulence genes by whole genome comparison of culture-attenuated Leptospira interrogans serovar Lai with its virulent, isogenic parent. Among the 11 pathogen-specific protein-coding genes in which non-synonymous mutations were found, a putative soluble adenylate cyclase with host cell cAMP-elevating activity, and two members of a previously unstudied ∼15 member paralogous gene family of unknown function were identified. This gene family was also uniquely found in the alpha-proteobacteria Bartonella bacilliformis and Bartonella australis that are geographically restricted to the Andes and Australia, respectively. How the pathogenic Leptospira and these two Bartonella species came to share this expanded gene family remains an evolutionary mystery. In vivo expression analyses demonstrated up-regulation of 10/11 Leptospira genes identified in the attenuation screen, and profound in vivo, tissue-specific up-regulation by members of the paralogous gene family, suggesting a direct role in virulence and host-pathogen interactions. The pathogenomic experimental design here is generalizable as a functional systems biology approach to studying bacterial pathogenesis and virulence and should encourage similar experimental studies of other pathogens. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS Neglected Tropical Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Animals en_US
dc.subject gene expression en_US
dc.subject nucleotide sequence en_US
dc.subject controlled study en_US
dc.subject reverse transcription polymerase chain reaction en_US
dc.subject bacterium culture en_US
dc.subject animal experiment en_US
dc.subject gene sequence en_US
dc.subject sequence homology en_US
dc.subject RNA 16S en_US
dc.subject bacterium detection en_US
dc.subject animal tissue en_US
dc.subject rat en_US
dc.subject Bartonella en_US
dc.subject animal cell en_US
dc.subject pathogenicity en_US
dc.subject gene en_US
dc.subject bacterial virulence en_US
dc.subject genome analysis en_US
dc.subject leptospirosis en_US
dc.subject Bartonella bacilliformis en_US
dc.subject Leptospirosis en_US
dc.subject Sequence Analysis, DNA en_US
dc.subject genomic DNA en_US
dc.subject Leptospira interrogans en_US
dc.subject Bacterial Proteins en_US
dc.subject genetic transcription en_US
dc.subject protein analysis en_US
dc.subject Virulence Factors en_US
dc.subject adenylate cyclase en_US
dc.subject bacterial pathogenesis en_US
dc.subject Bartonella australis en_US
dc.subject Cricetinae en_US
dc.subject cyclic AMP en_US
dc.subject DNA Mutational Analysis en_US
dc.subject Gene Expression Regulation, Bacterial en_US
dc.subject genetic transformation en_US
dc.subject Genome, Bacterial en_US
dc.subject hamster en_US
dc.subject immunodepletion en_US
dc.subject Mesocricetus en_US
dc.subject virulence associated gene en_US
dc.title Pathogenomic Inference of Virulence-Associated Genes in Leptospira interrogans en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pntd.0002468
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06
dc.relation.issn 1935-2735


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