Global transcriptomic profiling of pulmonary gene expression in an experimental murine model of Rickettsia conorii infection

Hema P. Narra, Abha Sahni, Kamil Khanipov, Yuriy Fofanov, Sanjeev Sahni

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number204
JournalGenes
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Rickettsia Infections
Rickettsia conorii
Gene Expression Profiling
Theoretical Models
Lung
aconitate decarboxylase
Genes
NK Cell Lectin-Like Receptors
Boutonneuse Fever
Infection
Eukaryotic Initiation Factor-2
Leukocyte L1 Antigen Complex
RNA Sequence Analysis
Ubiquitination
Oxidative Phosphorylation
Ticks
Ubiquitin
Heme
Chemokines
Cluster Analysis

Keywords

  • Antimicrobial peptides
  • C3H/HeN mice
  • Calgranulins
  • Guanylate-binding proteins
  • Ingenuity pathway analysis
  • Rickettsia
  • RNA sequencing
  • Transcriptome
  • Ubiquitination

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Global transcriptomic profiling of pulmonary gene expression in an experimental murine model of Rickettsia conorii infection. / Narra, Hema P.; Sahni, Abha; Khanipov, Kamil; Fofanov, Yuriy; Sahni, Sanjeev.

In: Genes, Vol. 10, No. 3, 204, 01.03.2019.

Research output: Contribution to journalArticle

@article{5c194140802042be9cd7052d4e096659,
title = "Global transcriptomic profiling of pulmonary gene expression in an experimental murine model of Rickettsia conorii infection",
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.",
keywords = "Antimicrobial peptides, C3H/HeN mice, Calgranulins, Guanylate-binding proteins, Ingenuity pathway analysis, Rickettsia, RNA sequencing, Transcriptome, Ubiquitination",
author = "Narra, {Hema P.} and Abha Sahni and Kamil Khanipov and Yuriy Fofanov and Sanjeev Sahni",
year = "2019",
month = "3",
day = "1",
doi = "10.3390/genes10030204",
language = "English (US)",
volume = "10",
journal = "Genes",
issn = "2073-4425",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",

}

TY - JOUR

T1 - Global transcriptomic profiling of pulmonary gene expression in an experimental murine model of Rickettsia conorii infection

AU - Narra, Hema P.

AU - Sahni, Abha

AU - Khanipov, Kamil

AU - Fofanov, Yuriy

AU - Sahni, Sanjeev

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - Antimicrobial peptides

KW - C3H/HeN mice

KW - Calgranulins

KW - Guanylate-binding proteins

KW - Ingenuity pathway analysis

KW - Rickettsia

KW - RNA sequencing

KW - Transcriptome

KW - Ubiquitination

UR - http://www.scopus.com/inward/record.url?scp=85064593084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064593084&partnerID=8YFLogxK

U2 - 10.3390/genes10030204

DO - 10.3390/genes10030204

M3 - Article

VL - 10

JO - Genes

JF - Genes

SN - 2073-4425

IS - 3

M1 - 204

ER -