Systems biology analysis of Brucella infected Peyer's patch reveals rapid invasion with modest transient perturbations of the host transcriptome

PloS One
Carlos A RossettiLeslie Garry Adams

Abstract

Brucella melitensis causes the most severe and acute symptoms of all Brucella species in human beings and infects hosts primarily through the oral route. The epithelium covering domed villi of jejunal-ileal Peyer's patches is an important site of entry for several pathogens, including Brucella. Here, we use the calf ligated ileal loop model to study temporal in vivo Brucella-infected host molecular and morphological responses. Our results document Brucella bacteremia occurring within 30 min after intraluminal inoculation of the ileum without histopathologic traces of lesions. Based on a system biology Dynamic Bayesian Network modeling approach (DBN) of microarray data, a very early transient perturbation of the host enteric transcriptome was associated with the initial host response to Brucella contact that is rapidly averted allowing invasion and dissemination. A detailed analysis revealed active expression of Syndecan 2, Integrin alpha L and Integrin beta 2 genes, which may favor initial Brucella adhesion. Also, two intestinal barrier-related pathways (Tight Junction and Trefoil Factors Initiated Mucosal Healing) were significantly repressed in the early stage of infection, suggesting subversion of mucosal epithelial barrier ...Continue Reading

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Jan 7, 2016·Annual Review of Animal Biosciences·Mariana X Byndloss, Renee M Tsolis
Nov 4, 2015·Frontiers in Cellular and Infection Microbiology·Yuehua KeZeliang Chen
Apr 22, 2015·The American Journal of Pathology·Paul de FigueiredoL Garry Adams
May 11, 2018·Current Medicinal Chemistry·Yuming DengQisheng Peng
Feb 21, 2019·Folia Microbiologica·Eric Daniel Avila-CalderónAraceli Contreras-Rodríguez
May 2, 2020·Pathogens·Raiany SantosSergio C Oliveira
Jul 13, 2019·Frontiers in Immunology·Karina A PasquevichJuliana Cassataro
Mar 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Aretha FiebigSean Crosson

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Datasets Mentioned

BETA
GSE41835

Methods Mentioned

BETA
biopsy
light microscopy
GTPases

Software Mentioned

BioSignature Discovery System (
GenePixPro
BiosignatureDS
Primer Express

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