Analysis of alternative mechanisms of iron acquisition by Moraxella catarrhalis and their role in pathogenesis
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Moraxella catarrhalis has emerged as the third leading bacterial cause of acute otitis media in young children and can cause sinusitis, pulmonary infections, nosocomial disease, and severe infections in immunocompromised patients. Otitis media is the leading cause of pediatric office visits, resulting in substantial direct and indirect costs for diagnosis and treatment. Due to these reasons, there has been an interest in vaccine development. M. catarrhalis is a strict human pathogen and this bacterium has developed multiple mechanisms to overcome many of the host pressures including iron limitations. Iron is an essential element required by most, if not all, organisms for survival and growth. Two iron acquisition systems have been described for M. catarrhalis . This organism expresses receptors for the human iron transport glycoproteins transferrin and lactoferrin. These receptor proteins are expressed in the outer membrane during iron limitation, and they are the target for human antibodies. It has been well established that the ferric uptake regulator (Fur) protein controls transcriptional regulation of iron-repressible outer membrane protein genes. These studies define an M. catarrhalis Fur-homologue capable of controlling the expression of proteins involved in iron acquisition by this organism. Many related Gram-negative bacterial species have many iron acquisition systems, which are often redundant. This work has revealed separate mechanisms by which M. catarrhalis can bind and utilize hemoglobin and heme for growth through the expression of novel outer membrane receptors MhuA and HumA, respectively. We have shown that this organism is able to sense iron concentrations and respond by altering outer membrane protein expression through a Fur-homologue, and M. catarrhalis is capable of utilizing hemoproteins for growth and survival in the human host.