Potential mechanisms of mucin-enhanced Acinetobacter baumannii virulence in the mouse model of intraperitoneal infection.

Porcine mucin has been commonly used to enhance the infectivity of bacterial pathogens including Acinetobacter baumannii in animal models, but the mechanisms for enhancement by mucin remain relatively unknown. In this study, using the mouse model of intraperitoneal (i.p.) mucin-enhanced A. baumannii infection we characterized the kinetics of bacterial replication and dissemination and the host innate immune responses, as well as their potential contribution to the mucin-enhanced bacterial virulence. We found that mucin, either admixed with or separately injected with the challenge bacterial inoculum, was able to enhance the tissue and blood burdens of A. baumannii strains of different virulence. Intraperitoneal injection of A. baumannii/mucin or mucin alone induced a significant, but comparable reduction of peritoneal macrophages and lymphocytes, accompanied with a significant neutrophil recruitment and early IL-10 responses, suggesting that the resulted inflammatory cellular and cytokine responses were largely induced by the mucin. Depletion of peritoneal macrophages or neutralization of endogenous IL-10 activities showed no effect on the mucin-enhanced infectivity. However, pre-treatment of mucin with iron chelator DIBI, but not deferoxamine, partially abolished its virulence enhancement ability and substitution of mucin with iron significantly enhanced the bacterial burdens in peritoneal cavity and lung. Taken together, our results favour the hypothesis that iron is at least partially contributing to the mucin-enhanced infectivity of A. baumannii in this model.