Pyoverdin is essential for virulence of Pseudomonas aeruginosa

Abstract

The role of pyoverdin, the main siderophore in iron-gathering capacity produced by Pseudomonas aeruginosa, in bacterial growth in vivo is controversial, although iron is important for virulence. To determine the ability of pyoverdin to compete for iron with the human iron-binding protein transferrin, wild-type P. aeruginosa ATCC 15692 (PAO1 strain) and PAO pyoverdin-deficient mutants were grown at 37؇C in bicarbonate-containing succinate medium to which apotransferrin had been added. Growth of the pyoverdin-deficient mutants was fully inhibited compared with that of the wild type but was restored when pyoverdin was added to the medium. Moreover, when growth took place at a temperature at which no pyoverdin production occurred (43؇C), the wild-type PAO1 strain behaved the same as the pyoverdin-deficient mutants, with growth inhibited by apotransferrin in the presence of bicarbonate and restored by pyoverdin supplementation. Growth inhibition was never observed in bicarbonate-free succinate medium, whatever the strain and the temperature for growth. In vivo, in contrast to results obtained with the wild-type strain, pyoverdin-deficient mutants demonstrated no virulence when injected at 10 2 CFU into burned mice. However, virulence was restored when purified pyoverdin originating from the wild-type strain was supplemented during the infection. These results strongly suggest that pyoverdin competes directly with transferrin for iron and that it is an essential element for in vivo iron gathering and virulence expression in P. aeruginosa. Rapid removal of iron from [ 59 Fe]ferritransferrin by pyoverdin in vitro supports this view.

The complex interplay of iron, biofilm formation, and mucoidy affecting antimicrobial resistance ofPseudomonas aeruginosa

“…Iron concentrations in the CF lung vary and measure anywhere between 2 and 130 lM (Mateos et al, 1998;Stites et al, 1998Stites et al, , 1999Reid et al, 2004;Gray et al, 2010;Gifford et al, 2011) and are correlated with the amount of inflammation and damage to lung tissues. Although P. aeruginosa encounters differing iron concentrations both temporally and spatially during pathogenesis, the importance of iron acquisition and iron-dependent regulation for a successful infection is well established (Cox, 1982;Meyer et al, 1996;Takase et al, 2000a, b). This study further establishes the importance of iron during pathogenesis, as higher iron concentrations allow for Fig.…”

“…Pseudomonas aeruginosa requires an abundance of iron during infection (Cox, 1982;Meyer et al, 1996;Takase et al, 2000a, b), but the sequestration of iron by host proteins from potential pathogens creates a substantial barrier to infection. Pseudomonas aeruginosa overcomes iron limitation through a variety of mechanisms, including the synthesis and secretion of two siderophores, pyoverdine and pyochelin, which can scavenge iron from host proteins and thus contribute to virulence (Cox, 1982;Takase et al, 2000a, b).…”

Limited Dispersal, Budding Dispersal, and Cooperation: An Experimental Study

“…Each subpopulation (approx. 10 6 cells from overnight KB cultures) was grown in a 30 mL tube containing 6 mL of Casamino acids medium (CAA; 5 g casamino acids, 1.18 g K 2 HPO 4 * 3H 2 O, 0.25 g MgSO 4 * 7H 2 O, per litre) supplemented with 20 mM NaHCO 3 (sodium bicarbonate) and 100 μgmL −1 human apo-transferrin (Sigma) (Meyer et al 1996;Griffin et al 2004). Apo-transferrin, combined with bicarbonate, is a powerful natural iron chelator (Schlabach and Bates 1975).…”

Diversity of siderophore‐mediated iron uptake systems in fluorescent pseudomonads: not only pyoverdines

“…PVD production was found to be of great importance for the capacity of P. aeruginosa to colonize mammalian hosts (Meyer et al ., 1996;Handfield et al ., 2000;Takase et al ., 2000).…”