title: Gallium induces the production of virulence factors in Pseudomonas aeruginosa.
abstract: The novel antimicrobial gallium is a nonredox iron III analogue with bacteriostatic and bactericidal properties, effective for the treatment of Pseudomonas aeruginosa in vitro and in vivo in mouse and rabbit infection models. It interferes with iron metabolism, transport, and presumably its homeostasis. As gallium exerts its antimicrobial effects by competing with iron, we hypothesized that it ultimately will lead cells to an iron deficiency status. As iron deficiency promotes the expression of virulence factors in vitro and promotes the pathogenicity of P. aeruginosa in animal models, it is anticipated that treatment with gallium will also promote the production of virulence factors. To test this hypothesis, the reference strain PA14 and two clinical isolates from patients with cystic fibrosis were exposed to gallium, and their production of pyocyanin, rhamnolipids, elastase, alkaline protease, alginate, pyoverdine, and biofilm was determined. Gallium treatment induced the production of all the virulence factors tested in the three strains except for pyoverdine. In addition, as the Ga-induced virulence factors are quorum sensing controlled, co-administration of Ga and the quorum quencher brominated furanone C-30 was assayed, and it was found that C-30 alleviated growth inhibition from gallium. Hence, adding both C-30 and gallium may be more effective in the treatment of P. aeruginosa infections.
authors.affiliation: Biochemistry Department, National Institute of Cardiology, Mexico City, Mexico.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: García-Contreras
authors.forename: Berenice
authors.initials: B
authors.lastname: Pérez-Eretza
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lira-Silva
authors.forename: Ricardo
authors.initials: R
authors.lastname: Jasso-Chávez
authors.forename: Rafael
authors.initials: R
authors.lastname: Coria-Jiménez
authors.forename: Adrián
authors.initials: A
authors.lastname: Rangel-Vega
authors.forename: Toshinari
authors.initials: T
authors.lastname: Maeda
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000382:microbiology; D005708:Gallium / Q000494:pharmacology*; D006801:Humans; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D037521:Virulence Factors; D005708:Gallium
keywords: Pseudomonas aeruginosa; biofilms; gallium nitrate; iron; virulence factors