Calcium protects bacteria against cadmium stress via reducing nitric oxide production and increasing iron acquisition

Cadmium (Cd) is a common toxic heavy metal in the environment, and bacteria have evolved different strategies against Cd-toxicity. Here, we found that marine bacterium Bacillus sp. 98 could significantly alleviate Cd-toxicity by recruiting calcium (Ca) for reducing excessive intracellular nitric oxide (NO) and enhancing iron acquisition. To investigate the underlying mechanisms, mass spectrometry-based proteomic analysis was applied to Bacillus sp. 98 after treated with Cd supplemented with or without Ca. Compared with bacterial cells treated with Cd only, the proteomic results showed that the expression level of NO synthase was markedly down-regulated, while the expression levels of NO dioxygenase, which is responsible for converting NO to nitrate, and proteins associated with iron uptake were profoundly enhanced when Ca was supplemented. Consistently, bacterial intracellular NO amount was dramatically increased after Bacillus sp. 98 was treated with Cd, and reversed to a normal level when Ca or iron was supplemented. Notably, Ca also protected bacteria against stresses from other heavy metals including Cu, Cr, Mn, Ni and Zn, and this self-protection strategy was adopted as well in zebrafish, which encourages us to develop Ca-associated products against heavy metals toxicity in the future.