Low-concentration Iron Promotes Klebsiella Pneumoniae Biofilm Formation by Suppressing Succinic Acid
Abstract Background: Klebsiella pneumoniae is widely distributed in water and plays a major role in both human and animal infections. Many K. pneumoniae strains form biofilms on various surfaces, enhancing their pathogenicity and resistance to antibiotics. New ways of inhibiting biofilm formation are needed. Iron is vital to the growth of microorganisms and the formation of biofilms due to its participation in various metabolic processes and its roles as an enzyme and protein cofactor. It is also present in groundwater. The aim of this study was to examine the effects of iron on K. pneumoniae biofilm formation and any associated metabolic changes.Results: Biofilm formation was enhanced to the greatest extent by the presence of 0.16 mM FeCl2, producing a denser structure under electron microscopy. The number of biofilm-forming and planktonic bacteria did not change, but protein and polysaccharide concentrations in the bacterial extracellular polymeric substances (EPS) were significantly increased by iron supplementation. To clarify this mechanism, intracellular metabolomic analysis was carried out, showing that the differential, down-regulated metabolites included succinic acid. Addition of succinic acid counteracted the biofilm-forming effect of iron, with no bactericidal side effects.Conclusion: This study demonstrates the importance of succinic acid and iron in Klebsiella pneumoniae biofilms, and provides insight into the formation of K. pneumoniae biofilms and direction for the development of new antibacterial agents.