Healthcare-associated, community-acquired and hospital-acquired Gram-negative bacteremias in a Turkish referral hospital

Abstract

Results: Addition of a soluble cocktail containing six protease inhibitors to a culture abolished the ability of B. pseudomallei to grow on ferritin as sole iron source. Addition of individual proteases contained in the cocktail revealed that two of them, AEBSF (4-[2-aminoethyl] benzene sulfonyl fluoride) and EDTA exhibited the most potent effect. These data are consistent with the previous finding that B. cenocepacia employs a serine protease for ferritin iron acquisition. Mutants that had all seven serine proteases individually deleted were successfully constructed. All mutants were still able to utilize ferritin as sole iron source at rates indistinguishable from the parent strain. The most plausible explanation for this observation is that B. pseudomallei does not employ a serine protease for ferritin iron acquisition. Conclusion: We have provided conclusive evidence that ferritin-iron acquisition by B. pseudomallei involves proteolytic degradation of ferritin but the protease(s) and other factors, e.g. transporters, involved in this process remain tobe identified.Defining a ferritin-iron acquisition pathway will substantially alter our current view of iron acquisition mechanisms in Gram-negative bacteria and provide a more complete picture of the pathogenesis of infection with B. pseudomallei.