A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii

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.

A Surface Exposed, Two-Domain Lipoprotein Cargo of a Type XI Secretion System Promotes Colonization of Host Intestinal Epithelia Expressing Glycans

“…Recent discoveries have revealed that members of the DUF560 family of OMPs are Type XI secretion systems (TXISS) that can move proteins across the outer membrane (Hooda et al, 2016(Hooda et al, , 2017Fantappie et al, 2017;da Silva et al, 2019;Bateman et al, 2021;Grossman et al, 2021). TXISS-dependent effectors include binding proteins for transferrin, lactoferrin, factor H, and heme.…”

“…X. nematophila HrpB and Acinetobacter baumanii HsmA are TXISS OMPs that secrete the soluble (non-lipidated) hemophores HrpC and HrpA, respectively. Xenorhabdus nematophila NilB is a TXISS OMP that, along with the associated lipoprotein NilC, is necessary for mutualistic colonization of the nematode Steinernema carpocapsae (Cowles and Goodrich-Blair, 2008;Hooda et al, 2016Hooda et al, , 2017Fantappie et al, 2017;da Silva et al, 2019;Bateman et al, 2021;Grossman et al, 2021).…”

Nutritional immunity: the battle for nutrient metals at the host–pathogen interface

“…Some Gram-negative pathogens encode multiple haem-acquisition systems such as the Phu and Has systems in P. aeruginosa 44 , suggesting that multiple non-redundant haem uptake systems benefit bacterial virulence. In the nosocomial pathogen Acinetobacter baumannii , the haemophore HphA is recognized by the two-component system receptor HphR 45 . Moreover, recent findings demonstrate that haem uptake efficiency is dependent upon bacterial toxin production in Vibrio cholerae 46 , raising the possibility that virulence factors may have a role in enhancing bacterial haem uptake in vivo.…”

Elucidation of the Correlation between Heme Distortion and Tertiary Structure of the Heme-Binding Pocket Using a Convolutional Neural Network

“…The roles of heme in heme proteins are diverse; for instance, heme acts as an electron carrier [ 1 , 2 ], an active site for enzymes such as oxidoreductases [ 3 , 4 ], an oxygen storage molecule [ 5 , 6 ], a ligand for proteins [ 7 , 8 ], and an iron storage molecule [ 9 ]. Hemophore proteins bind heme for its transport or storage [ 10 ]. Heme is classified into several types according to its peripheral groups ( Figure 1 ), and the most common heme types are heme b and c [ 11 , 12 ].…”