TY - JOUR
T1 - Transcriptomic analysis of the brucella melitensisrev.1 vaccine strain in an acidic environment
T2 - Insights into virulence attenuation
AU - Salmon-Divon, Mali
AU - Zahavi, Tamar
AU - Kornspan, David
N1 - Publisher Copyright:
© 2007 - 2019 Frontiers Media S.A. All Rights Reserved.
PY - 2019
Y1 - 2019
N2 - The live attenuated Brucella melitensis Rev.1 (Elberg-originated) vaccine strain is widely used to control the zoonotic infection brucellosis in small ruminants, but the molecular mechanisms underlying the attenuation of this strain have not been fully characterized. Following their uptake by the host cell, Brucella replicate inside a membrane-bound compartment-the Brucella-containing vacuole-whose acidification is essential for the survival of the pathogen. Therefore, identifying the genes that contribute to the survival of Brucella in acidic environments will greatly assist our understanding of its molecular pathogenic mechanisms and of the attenuated virulence of the Rev.1 strain. Here, we conducted a comprehensive comparative transcriptome analysis of the Rev.1 vaccine strain against the virulent reference strain 16M in cultures grown under either normal or acidic conditions. We found 403 genes that respond differently to acidic conditions in the two strains (FDR < 0.05, fold change ≥ 2). These genes are involved in crucial cellular processes, including metabolic, biosynthetic, and transport processes. Among the highly enriched genes that were downregulated in Rev.1 under acidic conditions were acetyl-CoA synthetase, aldehyde dehydrogenase, cell division proteins, a cold-shock protein, GroEL, and VirB3. The downregulation of these genes may explain the attenuated virulence of Rev.1 and provide new insights into the virulence mechanisms of Brucella.
AB - The live attenuated Brucella melitensis Rev.1 (Elberg-originated) vaccine strain is widely used to control the zoonotic infection brucellosis in small ruminants, but the molecular mechanisms underlying the attenuation of this strain have not been fully characterized. Following their uptake by the host cell, Brucella replicate inside a membrane-bound compartment-the Brucella-containing vacuole-whose acidification is essential for the survival of the pathogen. Therefore, identifying the genes that contribute to the survival of Brucella in acidic environments will greatly assist our understanding of its molecular pathogenic mechanisms and of the attenuated virulence of the Rev.1 strain. Here, we conducted a comprehensive comparative transcriptome analysis of the Rev.1 vaccine strain against the virulent reference strain 16M in cultures grown under either normal or acidic conditions. We found 403 genes that respond differently to acidic conditions in the two strains (FDR < 0.05, fold change ≥ 2). These genes are involved in crucial cellular processes, including metabolic, biosynthetic, and transport processes. Among the highly enriched genes that were downregulated in Rev.1 under acidic conditions were acetyl-CoA synthetase, aldehyde dehydrogenase, cell division proteins, a cold-shock protein, GroEL, and VirB3. The downregulation of these genes may explain the attenuated virulence of Rev.1 and provide new insights into the virulence mechanisms of Brucella.
KW - Acid stress
KW - Attenuation
KW - Brucella melitensis 16M
KW - Brucella melitensis Rev.1
KW - RNA-Seq
KW - Transcriptomic analyses
KW - Virulence
UR - http://www.scopus.com/inward/record.url?scp=85065924258&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2019.00250
DO - 10.3389/fmicb.2019.00250
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AN - SCOPUS:85065924258
SN - 1664-302X
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
IS - FEB
M1 - 250
ER -