title: A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus.
abstract: Pseudomonas aeruginosa establishes airway infections in Cystic Fibrosis patients. Here, we investigate the molecular interactions between P. aeruginosa and airway mucus secretions (AMS) derived from the primary cultures of normal human tracheal epithelial (NHTE) cells. PAO1, a prototype strain of P. aeruginosa, was capable of proliferating during incubation with AMS, while all other tested bacterial species perished. A PAO1 mutant lacking PA4834 gene became susceptible to AMS treatment. The ΔPA4834 mutant was grown in AMS supplemented with 100 μM ferric iron, suggesting that the PA4834 gene product is involved in iron metabolism. Consistently, intracellular iron content was decreased in the mutant, but not in PAO1 after the AMS treatment. Importantly, a PAO1 mutant unable to produce both pyoverdine and pyochelin remained viable, suggesting that these two major siderophore molecules are dispensable for maintaining viability during incubation with AMS. The ΔPA4834 mutant was regrown in AMS amended with 100 μM nicotianamine, a phytosiderophore whose production is predicted to be mediated by the PA4836 gene. Infectivity of the ΔPA4834 mutant was also significantly compromised in vivo. Together, our results identify a genetic element encoding a novel iron acquisition system that plays a previously undiscovered role in P. aeruginosa airway infection.
authors.affiliation: Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.
authors.forename: Mia
authors.initials: M
authors.lastname: Gi
authors.affiliation: Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.
authors.forename: Kang-Mu
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.|Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005290:Ferric Compounds / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D050296:Microbial Viability / Q000187:drug effects; D009093:Mucus / Q000737:chemistry*; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D061251:Primary Cell Culture; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D017262:Siderophores / Q000096:biosynthesis / Q000172:deficiency; D013844:Thiazoles / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000378:metabolism
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D009842:Oligopeptides; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; C082893:nicotianamine; D001383:Azetidinecarboxylic Acid; C025316:pyochelin; C042453:pyoverdin; D007501:Iron; C024555:ferric chloride