A horizontally acquired transcription factor coordinates Salmonella adaptations to host microenvironments

Area of Science:

• Microbiology
• Molecular Biology
• Genomics

Background:

• Salmonella employs type III secretion systems (T3SSs) to infect hosts, with expression regulated by transcription factors like HilA and SsrB.
• These factors and their associated systems are often encoded by horizontally acquired genes, highlighting their role in bacterial adaptation.
• Previous studies primarily focused on T3SS substrates linked to these transcription factors.

Purpose of the Study:

• To comprehensively investigate the regulatory targets of Salmonella transcription factors HilA and SsrB using quantitative proteomics.
• To determine the extent of the HilA and SsrB regulons beyond known T3SS-related proteins.
• To explore novel functions regulated by SsrB that contribute to Salmonella's intracellular survival and adaptation.

Main Methods:

• Quantitative proteomics was employed to measure the abundance of 2,149 proteins in Salmonella strains lacking hilA or ssrB.
• Comparative analysis of protein expression profiles under hilA or ssrB regulation was performed.
• Bioinformatic and functional analyses were used to identify regulated pathways and processes.

Main Results:

• The HilA regulon was largely confined to proteins involved in direct intestinal epithelium interactions.
• The SsrB regulon extended significantly beyond T3SS-2 substrates, encompassing a diverse set of proteins.
• SsrB was found to regulate resistance to reactive oxygen species (via SodCI and bacterioferritin) and down-regulate flagellar motility.

Conclusions:

• SsrB plays a broader role than previously understood, coordinating host cell manipulation with bacterial adaptation to the intracellular niche.
• SsrB-regulated processes enhance Salmonella's survival by managing oxidative stress and reducing motility within host cells.
• The findings underscore the potential of T3SS-associated transcription factors in orchestrating complex host-pathogen interactions.