Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster.
The host innate immune defense protein lipocalin 2 binds bacterial enterobactin siderophores to limit bacterial iron acquisition. To counteract this host defense mechanism bacteria have acquired the iroA gene cluster, which encodes enzymatic machinery and transporters that revitalize enterobactin in the form of salmochelin. The iroB enzyme introduces glucosyl residues at the C5 site on 2,3-dihydroxybenzoylserine moieties of enterobactin and thereby prevents lipocalin 2 binding. Additional strategies to evade lipocalin 2 have evolved in other bacteria, such as Mycobacteria tuberculosis and Bacillus anthracis. Targeting these specialized bacterial evasion strategy may provide a mechanism to reinvigorate lipocalin 2 in defense against specific pathogens.
Smith
Kelly D
KD
Department of Pathology, University of Washington, 1959 NE Pacific St. HSB E504, Box 357470, Seattle, WA 98195, United States. kelsmith@u.washington.edu
D000209:Acute-Phase Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D015195:Drug Design; D004758:Enterobactin / Q000031:analogs & derivatives / Q000502:physiology; D018390:Gene Targeting; D005960:Glucosides; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D005810:Multigene Family / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*
D000209:Acute-Phase Proteins; D001425:Bacterial Outer Membrane Proteins; D005960:Glucosides; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C083821:iroA protein, bacteria; C508254:salmochelin S4; D004758:Enterobactin; D007501:Iron
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