Host and pathogen transcriptional profiles of acute Brucella melitensis infection

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Title: Host and pathogen transcriptional profiles of acute Brucella melitensis infection
Author: Rossetti, Carlos Alberto
Abstract: The parallel gene expression profiles of Brucella melitensis and the host have not been elaborated . In this study , I analyze and discuss the transcriptional profiles of B . melitensis invasive -associated genes , the expression profile of intracellular B . melitensis and B . melitensis -infected non -phagocytic cells in the first 12 h post -infection (PI ) , and the in vivo temporal global transcriptome of both B . melitensis and the infected bovine host in the first 4 h PI . The initial study found that B . melitensis at late -log phase of growth were more invasive in non -phagocytic cells than at early -log or stationary growth phase . Microarray -based studies identified 454 Brucella genes differentially expressed between the most and the least invasive growth phases . Additionally , B . melitensis strains with transposon interrupted in loci BMEII0380 (acrA ) and BMEI1538 (hypothetical protein ) were found to be deficient in internalization compare with the wild -type strain . A second experiment was designed with the goal of characterizing host and pathogen transcriptome in parallel . For detecting intracellular Brucella gene expression , a combined protocol consisting of a linear amplification of sense -stranded RNA biased to pathogen transcripts to the previously enriched host :pathogen RNA mixed sample , was developed . RNA samples were hybridized on human and Brucella cDNA microarrays , which analysis revealed a common down -regulation transcriptional profile at 4 h PI that was reverse at 12 h PI . The integrity of B . melitensis virB operon and the expression of host MAPK1 were confirmed as critical for early B . melitensis intracellular survival and replication in non -phagocytic cells . Finally , a temporal morphological and molecular characterization of the initial B . melitensis :bovine host interaction using a calf ileal loop model was performed . B . melitensis was isolated from intestinal Peyer ?s patches as soon as 15 min and from systemic blood after 30 min postintra luminal inoculation . Microarray results revealed a common transcriptional profile in Brucella , but two different transcriptional profiles were identified in the host in the first 4 h PI . The importance of differentially expressed biological processes , pathways and individual genes in the initial Brucella pathogenesis is discussed .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1636
Date: 2009-05-15


Host and pathogen transcriptional profiles of acute Brucella melitensis infection. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1636 .

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