Poly-Gamma-Glutamic Acid Secretion Protects Bacillus subtilis from Zinc and Copper Intoxication

Zinc and copper are essential micronutrients that serve as a cofactors for numerous enzymes. However, when present at elevated concentrations, zinc and copper are highly toxic to bacteria. To combat the effects of zinc and copper excess, bacteria have evolved a wide array of defense mechanisms. Here, we show that the Gram-positive soil bacterium, Bacillus subtilis, produces the extracellular polymeric substance, poly-gamma-glutamate (gamma-PGA) as a protective mechanism in response to zinc and copper excess. Furthermore, we provide evidence that zinc and copper dependent gamma-PGA production is independent of the DegS-DegQ two-component regulatory system and likely occurs at a posttranscriptional level through the small protein, PgsE. These data provide new insight into bacterial metal resistance mechanisms and contribute to our understanding of the regulation of bacterial gamma-PGA biosynthesis. IMPORTANCE Zinc and copper are potent antimicrobial compounds. As such, bacteria have evolved a diverse range of tools to prevent metal intoxication. Here, we show that the Gram-positive model organism, Bacillus subtilis, produces poly-gamma-glutamic acid (gamma-PGA) as a protective mechanism against zinc and copper intoxication and that zinc and copper dependent gamma-PGA production occurs by a yet undefined mechanism independent of known gamma-PGA regulation pathways.

Automated summary

Zinc and copper are essential micronutrients that are toxic to bacteria at elevated concentrations. Bacteria have evolved defense mechanisms, including the production of extracellular polymeric substance poly-gamma-glutamate (gamma-PGA) to combat zinc and copper excess. This study provides new insight into metal resistance mechanisms and regulation of bacterial gamma-PGA biosynthesis.