Analysis of the ArcA regulon in anaerobically grown Salmonella enterica sv. Typhimurium

Matthew R Evans,Jessica Jones-Carson,Andres Vazquez-Torres,Hosni M Hassan,Steffen Porwollik,Ryan C Fink,Michael Mcclelland

doi:10.1186/1471-2180-11-58

Abstract

BackgroundSalmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host. In Escherichia coli, ArcA (Aerobic Respiratory Control) helps the cells to sense and respond to the presence of dioxygen. The global role of ArcA in E. coli is well characterized; however, little is known about its role in anaerobically grown S. Typhimurium.ResultsWe compared the transcriptional profiles of the virulent wild-type (WT) strain (ATCC 14028s) and its isogenic arcA mutant grown under anaerobic conditions. We found that ArcA directly or indirectly regulates 392 genes (8.5% of the genome); of these, 138 genes are poorly characterized. Regulation by ArcA in S. Typhimurium is similar, but distinct from that in E. coli. Thus, genes/operons involved in core metabolic pathways (e.g., succinyl-CoA, fatty acid degradation, cytochrome oxidase complexes, flagellar biosynthesis, motility, and chemotaxis) were regulated similarly in the two organisms. However, genes/operons present in both organisms, but regulated differently by ArcA in S. Typhimurium included those coding for ethanolamine utilization, lactate transport and metabolism, and succinate dehydrogenases. Salmonella-specific genes/operons regulated by ArcA included those required for propanediol utilization, flagellar genes (mcpAC, cheV), Gifsy-1 prophage genes, and three SPI-3 genes (mgtBC, slsA, STM3784). In agreement with our microarray data, the arcA mutant was non-motile, lacked flagella, and was as virulent in mice as the WT. Additionally, we identified a set of 120 genes whose regulation was shared with the anaerobic redox regulator, Fnr.Conclusion(s)We have identified the ArcA regulon in anaerobically grown S. Typhimurium. Our results demonstrated that in S. Typhimurium, ArcA serves as a transcriptional regulator coordinating cellular metabolism, flagella biosynthesis, and motility. Furthermore, ArcA and Fnr share in the regulation of 120 S. Typhimurium genes.

Highlights

IntroductionTyphimurium) is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host
All the genes showing significant differential expression were classified into clusters of orthologous groups (COGs) [34,35,36] as defined by the National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm. nih.gov/COG (Table 3)
We showed that ArcA is involved in energy metabolism, flagella biosynthesis, and motility

Summary

Introduction

Typhimurium) is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host. In Escherichia coli, ArcA (Aerobic Respiratory Control) helps the cells to sense and respond to the presence of dioxygen. The global role of ArcA in E. coli is well characterized; little is known about its role in anaerobically grown S. Typhimurium) is a Gram-negative intracellular pathogen that causes gastroenteritis in the human host. The infection proceeds via two main stages: invasion and systemic infection. The pathogen adheres and colonizes the intestines gaining access to the epithelial cells. Salmonella crosses the epithelial cells and gets internalized by the

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