Investigation of a Heme Uptake System in Acinetobacter baumannii
Iron is an essential micronutrient required for bacterial growth and survival. Heme is the largest source of iron in humans, but is inaccessible as it is tightly bound by proteins like hemoglobin. Bacteria rely on specialized protein machinery to capture host heme. Therefore, these pathways are attractive therapeutic targets which necessitates an in depth understanding of how they function. Two gene clusters predicted to function in heme acquisition in the opportunistic pathogen, Acinetobacter baumannii, are examples of such pathways requiring further characterization. This is especially important as A. baumannii is an increasing threat to global health due to its extensive antibiotic resistance. In this thesis, I show that one of the predicted gene clusters functions to support growth in hemoprotein scarce conditions. This gene cluster encodes an outer membrane translocon that secretes a hemophore called HphA into the environment. HphA binds to Hb and passively scavenges its heme, which is then shuttled to the outer membrane hemophore receptor, HphR, for subsequent uptake. The HphR-heme uptake pathway plays a crucial role in A. baumannii virulence and thus, has potential for future therapeutic interventions.
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