Abstract
Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
Highlights
Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets
Heme cluster 2 is important for heme uptake from human hemoproteins
These gene clusters appear redundant as a double knockout mutant exhibited clear growth defects in abundant Hb and not in rich media compared to the single mutants (Fig. 1c; Supplementary Fig. 1e, f)
Summary
Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. We study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. Increased sensitivity of LAC-4 to the toxic heme analog, gallium protoporphyrin (GaPPIX), which blocked the spread of LAC-4 from the lungs into the blood in a mouse infection model indirectly demonstrated the importance of the hemO cluster to heme uptake and the central role of heme in A. baumannii disease progression[8]. The presence of heme cluster 2 in an entire panel of A. baumannii multidrug-resistant clinical isolates involved in hospital outbreaks further highlights the importance of this system in the context of disease[9]
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