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Genes 2019, 10(3), 204; https://doi.org/10.3390/genes10030204

Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection

1
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
2
Department of Pharmacology, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Authors to whom correspondence should be addressed.
Received: 11 February 2019 / Revised: 27 February 2019 / Accepted: 4 March 2019 / Published: 8 March 2019
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

Mediterranean spotted fever develops from an infection with Rickettsia conorii, an obligate intracellular, Gram-negative, endotheliotropic, and tick-transmitted bacterial pathogen, and is an acute, febrile illness that can progress to life-threatening complications if not diagnosed and treated early with effective antibiotics. Despite significant morbidity and mortality, little is known about changes in gene expression that determine the host responses during in vivo infection. We have investigated the transcriptional landscape of host lungs as a prominently affected organ system in an established murine model of infection by RNA-sequencing. Ingenuity pathway analysis resulted in the identification of 1332 differentially expressed genes and 292 upstream regulators. Notably, genes encoding for ubiquitin D, aconitate decarboxylase, antimicrobial peptides, calgranulins, cytokines and chemokines, and guanylate binding proteins were highly up-regulated, whereas those involved in hemoglobin biosynthesis and heme homeostasis were significantly down-regulated. Amongst response regulators, nucleotide-binding oligomerization domain-containing protein 2 and killer cell lectin-like receptors were differentially expressed, and gene clustering revealed eukaryotic initiation factor-2, oxidative phosphorylation, and ubiquitination as the predominantly activated biological pathways. Collectively, this first global transcriptomic profiling has identified R. conorii-induced regulation of novel genes and pathways in the host lungs, further in-depth investigation of which will strengthen our understanding of the pathogenesis of human rickettsioses. View Full-Text
Keywords: Rickettsia; C3H/HeN mice; RNA sequencing; transcriptome; ingenuity pathway analysis; antimicrobial peptides; guanylate-binding proteins; calgranulins; ubiquitination Rickettsia; C3H/HeN mice; RNA sequencing; transcriptome; ingenuity pathway analysis; antimicrobial peptides; guanylate-binding proteins; calgranulins; ubiquitination
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Narra, H.P.; Sahni, A.; Khanipov, K.; Fofanov, Y.; Sahni, S.K. Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection. Genes 2019, 10, 204.

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