1 / 2018-10-24 22:09:49

The molecular mechanism of gallium uptake by Pseudomonas aeruginosa

Pseudomonas aeruginosa, gallium, uptake system

Ga(III) has successfully been applied for antibacterial metal-drug. But the transport system of Ga(III) into P. aeruginosa is not revealed so far. Given the similarity of Ga(III) and iron between ionic radius and coordination, most ferric-binding proteins could interact with Ga(III) in vivo, we screened P. aeruginosa mutants defective in iron uptake systems and finally found that the hitA (GenBank: PA2487) and hitB (GenBank: PA2488) genes were deleted respectively leading to a increasing tolerance ability of gallium nitrate against P. aeruginosa. Therefire, we speculated that HitA and HitB were involved in the Ga(III) uptake in P. aeruginosa. Here we solved the crystal structures, including the apo-form HitA, the Fe3+-bound HitA and the Ga(III)-bound HitA, which revealed that the similarity coordinate between iron and Ga(III), which further confirmed that Ga(III) via the HitABC iron transport system entered P. aeruginosa and perturb bacterial iron metabolic balance. Identification of Ga(III) uptake pathway spreads the research of antimicrobial mechanism of Ga-drugs, which lays a theoretical foundation for the development of new metal drugs.