A Bacterial Pathogen Senses Host Mannose to Coordinate Virulence

Area of Science:

• Microbiology
• Molecular Biology
• Pathogen-host interactions

Background:

• Bacterial pathogens often activate virulence genes in response to host cues.
• Identifying these host-associated signals has been challenging for many pathogens.

Purpose of the Study:

• To identify host-derived signals that trigger virulence gene expression in the fish pathogen Edwardsiella piscicida.
• To elucidate the molecular mechanism by which Edwardsiella piscicida senses and responds to the host environment.

Main Methods:

• Generated a genome-scale transposon mutant library of Edwardsiella piscicida.
• Quantified mutant fitness during intracellular growth in macrophages and in turbot (Scophthalmus maximus).
• Identified and characterized the EvrA transcription activator and its interaction with mannose-6-phosphate (man-6P).

Main Results:

• Identified EvrA as a transcription activator that upregulates the virulence regulator esrB.
• Demonstrated that EvrA is directly activated by mannose-6-phosphate (man-6P), derived from imported mannose.
• Showed that EvrA-deficient mutants are attenuated in turbot, and exogenous mannose enhances virulence.

Conclusions:

• Bacterial pathogens can sense host environments through direct binding of host-derived sugars to transcription factors.
• Mannose-6-phosphate (man-6P) acts as a direct signal for activating virulence programs in Edwardsiella piscicida.
• This mechanism allows pathogens to tailor virulence gene expression to host conditions.