Neutrophil gelatinase-associated lipocalin (NGAL) facilitates intracellular iron transport by shuttling a complex of Fe3+ and three 2,5-dihydroxybenzoic acid (DHBA) molecules. NGAL, along with serum albumin, also inhibits bacterial growth by intercepting bacterial siderophores, bacterially produced-iron chelating agents, before they return to bacteria. It has been shown that nonenzymatic glycation, which occurs more rapidly with increasing blood sugar concentration, decreases serum albumin's affinity for siderophores. This lowered affinity allows bacteria to obtain iron and grow more quickly. We hypothesize that the affinity of NGAL for its native substrates is similarly hindered by nonenzymatic glycation, resulting in destabilization of iron homeostasis and suppression of immune response in diabetic individuals. This work used QCM-D to compare the binding strengths of the Fe(DHBA)3 complex to glycated and nonglycated NGAL. This research has implications for preventing infections in diabetics, especially infections caused by siderophore-dependent bacteria such as M. tuberculosis.

Glycation of neutrophil gelatinase-associated lipocalin and its effects on iron homeostasis in diabetics: A QCM-D study

243rd National Meeting (2012)

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