Zinc excess impairs Mycobacterium bovis growth through triggering a Zur-IdeR-iron homeostasis signal pathway

Area of Science:

• Microbiology
• Molecular Biology
• Infectious Diseases

Background:

• Zinc is essential but toxic in excess, acting as an innate defense against bacterial infections, particularly mycobacteria.
• The signaling pathways linking zinc excess to iron homeostasis in mycobacteria are not well understood.
• Understanding these pathways is crucial for developing new strategies against mycobacterial pathogens like Mycobacterium tuberculosis.

Purpose of the Study:

• To characterize a novel signaling pathway in Mycobacterium bovis involving zinc excess and iron homeostasis.
• To elucidate the roles of the Zur and IdeR regulators in modulating bacterial growth under zinc toxicity.
• To explore the crosstalk between zinc and iron homeostasis in mycobacteria.

Main Methods:

• Characterization of the Zur-IdeR-iron homeostasis pathway in Mycobacterium bovis.
• Analysis of gene transcription and protein interactions under conditions of zinc excess.
• Genetic manipulation (deletion and silencing) of zur and ideR genes to assess their impact on bacterial growth and iron accumulation.

Main Results:

• A novel Zur-IdeR-iron homeostasis pathway was identified in Mycobacterium bovis.
• Excess zinc disrupts the Zur-IdeR interaction, repressing ideR transcription and promoting iron uptake gene expression.
• This leads to intracellular iron accumulation, reduced bacterial survival under zinc stress, and impaired growth upon ideR silencing.

Conclusions:

• Zinc excess triggers a pathway in M. bovis that disrupts iron homeostasis via the Zur-IdeR interaction.
• This disruption results in increased intracellular iron, ultimately impairing bacterial growth and survival.
• The findings reveal a conserved antimicrobial mechanism and highlight the complex interplay between zinc and iron metabolism in bacteria.