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https://www.arca.fiocruz.br/handle/icict/20069
A PUTATIVE REGULATORY GENETIC LOCUS MODULATES VIRULENCE IN THE PATHOGEN LEPTOSPIRA INTERROGANS
Genética
Proteínas da membrana bacteriana
Cricetinae
Animais
Rim
Author
Affilliation
Institut Pasteur. Biology of Spirochetes Unit. Paris, France
Institut Pasteur de Nouvelle-Calédonie. Association Pasteur International Network. Nouméa, New Caledonia
Institut Pasteur. Biology of Spirochetes Unit. Paris, France
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Yale School of Public Health. Department of Epidemiology of Microbial Disease. New Haven, Connecticut, USA
Yale School of Public Health. Department of Epidemiology of Microbial Disease. New Haven, Connecticut, USA
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Institut Pasteur de Nouvelle-Calédonie. Association Pasteur International Network. Nouméa, New Caledonia
Institut Pasteur. Biology of Spirochetes Unit. Paris, France
Institut Pasteur de Nouvelle-Calédonie. Association Pasteur International Network. Nouméa, New Caledonia
Institut Pasteur. Biology of Spirochetes Unit. Paris, France
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Yale School of Public Health. Department of Epidemiology of Microbial Disease. New Haven, Connecticut, USA
Yale School of Public Health. Department of Epidemiology of Microbial Disease. New Haven, Connecticut, USA
Institut Pasteur. Plate-Forme Transcriptome et Epigenome. Departement Génomes et Génétique. Paris, France
Institut Pasteur de Nouvelle-Calédonie. Association Pasteur International Network. Nouméa, New Caledonia
Institut Pasteur. Biology of Spirochetes Unit. Paris, France
Abstract
Limited research has been conducted on the role of transcriptional regulators in relation to virulence in Leptospira interrogans, the etiological agent of leptospirosis. Here, we identify an L. interrogans locus that encodes a sensor protein, an anti-sigma factor antagonist, and two genes encoding proteins of unknown function. Transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. This lb139 insertion mutant (the lb139(-) mutant) displayed attenuated virulence in the hamster model of infection and reduced motility in vitro. Whole-transcriptome analyses using RNA sequencing revealed the downregulation of 115 genes and the upregulation of 28 genes, with an overrepresentation of gene products functioning in motility and signal transduction and numerous gene products with unknown functions, predicted to be localized to the extracellular space. Another significant finding encompassed suppressed expression of the majority of the genes previously demonstrated to be upregulated at physiological osmolarity, including the sphingomyelinase C precursor Sph2 and LigB. We provide insight into a possible requirement for transcriptional regulation as it relates to leptospiral virulence and suggest various biological processes that are affected due to the loss of native expression of this genetic locus.
Keywords in Portuguese
Leptospira interrogansGenética
Proteínas da membrana bacteriana
Cricetinae
Animais
Rim
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