title: Norepinephrine represses the expression of toxA and the siderophore genes in Pseudomonas aeruginosa.
abstract: Among the different extracellular virulence factors produced by Pseudomonas aeruginosa are exotoxin A (ETA) and the pyoverdine and pyochelin siderophores. Production of ETA and the siderophores requires the function of the iron-starvation sigma factor PvdS, the transcriptional activator RegA, and the AraC-activator PchR. Iron represses the production of ETA and the siderophores by repressing the expression of pvdS, regA, and pchR. PvdS regulates the expression of the ETA gene, toxA, regA, and the pyoverdine synthesis genes. The catecholamine norepinephrine enhances the growth of pathogenic bacteria by transferring iron from host-binding proteins. In this study, we elucidated the mechanism by which norepinephrine and other catecholamines induce P. aeruginosa growth. We also investigated whether norepinephrine regulates the expression of toxA and the siderophore genes, and the mechanism of this regulation. Norepinephrine enhanced the growth of P. aeruginosa by supplying iron from transferrin. This provision of iron repressed the expression of toxA, the pyoverdine genes pvdD and pvdE, and their regulators, pvdS, regA, and pchR, suggesting that norepinephrine accomplishes this repression through PvdS and PchR. Additionally, norepinephrine bypassed PvdS and supported the growth of a pvdS deletion mutant, indicating that norepinephrine transfers iron to P. aeruginosa independent of pyoverdine. Thus, norepinephrine apparently influences the pathogenesis of P. aeruginosa by affecting its pattern of growth and the production of virulence factors.
authors.affiliation: Department of Pharmacy Practice, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.forename: Mark
authors.initials: M
authors.lastname: Lyte
authors.forename: Primrose P
authors.initials: PP
authors.lastname: Freestone
authors.forename: Aziba
authors.initials: A
authors.lastname: Ajmal
authors.forename: Jane A
authors.initials: JA
authors.lastname: Colmer-Hamood
authors.forename: Abdul N
authors.initials: AN
authors.lastname: Hamood
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005098:Exotoxins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D017262:Siderophores / Q000096:biosynthesis*; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D007501:Iron; D009638:Norepinephrine; D017262:Siderophores; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
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