Abstract
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.
Highlights
Brucella are facultative intracellular bacteria that are responsible for brucellosis—a zoonotic infection that causes abortions and sterility in ruminants, pigs, dogs, and rodents, and a severely debilitating febrile illness in humans (Ko and Splitter, 2003; von Bargen et al, 2012)
We used RNA-seq to conduct a comprehensive comparative transcriptomic analysis of the gene expression profiles of the Rev.1 and 16M B. melitensis strains, grown either under low-pH conditions that mimic the intracellular niche of the Brucella-containing vacuole (BCV) or normal-pH conditions
For each separate strain, we report the genes that are differentially expressed (DE) between bacteria grown under normal-pH conditions and those grown under low-pH conditions
Summary
Brucella are facultative intracellular bacteria that are responsible for brucellosis—a zoonotic infection that causes abortions and sterility in ruminants, pigs, dogs, and rodents, and a severely debilitating febrile illness in humans (Ko and Splitter, 2003; von Bargen et al, 2012). One factor that crucially contributes to the virulence of Brucella is their ability to survive within various host cells, where they are inaccessible to the humoral immune response of the host (Delrue et al, 2004). As the T4SS system (and, especially, the proteins VirB3–6 and VirB8–11) plays a crucial role in inhibiting the host immune response and in the intracellular survival and replication of Brucella within the host cells (Comerci et al, 2001; den Hartigh et al, 2008; Ke et al, 2015; Smith et al, 2016), the ability of Brucella to survive within the acidic conditions of the BCV is key to their pathogenesis and can be used to study the underlying mechanisms (Roop et al, 2009)
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