Abstract
Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the most used models for bacterial pathogenesis and successful infection requires its adaptation to the low oxygen environment in host gastrointestinal tracts. Central to this process is the Arc (aerobic respiratory control) two-component regulatory system that contains a sensor kinase ArcB and a response regulator ArcA. Nevertheless, a comprehensive profile of the ArcA regulon on the proteome level is still lacking in S. Typhimurium. Here we quantitatively profiled Salmonella proteome during anaerobiosis in an arcA-deleting mutant compared with its parental strain. In addition to known processes under its control, notably we found that ArcA represses ethanolamine utilization by directly binding to the promoter region of the eut operon. Furthermore, we found opposing changes of several bacterial genes on the protein and transcript levels in the arcA-deleting mutant including the virulence genes of Salmonella pathogenicity island 1 (SPI-1), thereby indicating potentially prevalent post-transcriptional regulatory mechanisms. Altogether, our study provides important new insights into ArcA-dependent bacterial physiology and virulence during Salmonella anaerobiosis.
Highlights
We provide evidence that the regulation of the trichloroacetic acid (TCA) cycle by ArcA is partially mediated by its repression of the transcription factor YdcI
Bacterial Strains and Culture Conditions—The Salmonella enterica serovar Typhimurium wild-type strain SL1344 and its isogenic arcA mutant were maintained frozen at Ϫ80 °C in the peptone solution (2% peptone, 25% glycerol)
Typhimurium and Its Isogenic ⌬arcA Strain During Anaerobiosis—To globally define the ArcAB regulon, we quantitatively examined the proteome of wild-type S
Summary
After bacterial internalization into host cells, SPI-2 T3SS is activated and plays a major role in promoting intracellular survival and replication [1,2,3]. Typhimurium to different respiratory conditions is the Arc two-component system (TCS). It comprises the transmembrane sensor kinase ArcB and the cytosolic cognate response regulator ArcA [5, 6]. Typhimurium ATCC 14028s wild-type (WT) and its isogenic ⌬arcA mutant under anaerobic conditions [14]. In addition to the central metabolism regulated as in E. coli, Salmonella ArcA controls the expression of distinct pathways such as repression of ethanolamine utilization and activation propanediol metabolism. A proteomic landscape of the ArcA-regulated pathways during Salmonella anaerobiosis has been lacking.
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