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

被引:28
作者
Bateman, Thomas J. [1 ]
Shah, Megha [1 ]
Ho, Timothy Pham [1 ]
Shin, Hyejin Esther [1 ]
Pan, Chuxi [1 ]
Harris, Greg [2 ]
Fegan, Jamie E. [3 ]
Islam, Epshita A. [1 ]
Ahn, Sang Kyun [3 ]
Hooda, Yogesh [1 ]
Gray-Owen, Scott D. [3 ]
Chen, Wangxue [2 ]
Moraes, Trevor F. [1 ]
机构
[1] Univ Toronto, Dept Biochem, Toronto, ON, Canada
[2] Natl Res Council Canada, Human Hlth Therapeut HHT Res Ctr, Ottawa, ON, Canada
[3] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
关键词
ESCHERICHIA-COLI; OUTER-MEMBRANE; HEMOGLOBIN; PROTEIN; LIPOPROTEINS; HAPTOGLOBIN; RESISTANCE; TOLERANCE; INFECTION; REVEALS;
D O I
10.1038/s41467-021-26545-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Nutrient acquisition is crucial for the growth of pathogens within their hosts. Here, Bateman et al. identify a set of proteins required for heme uptake from host hemoglobin and serum albumin in the pathogen Acinetobacter baumannii.
引用
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页数:13
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