Question

a) What role does Yersiniabactin play for Y. pestis?

b) Why does Y. pestis need Yersiniabactin to be fatal?

c) Circle six donor atoms on the diagram that would bind to Fe(III). Justify your choices.

d) If Fe(III) is reduced to Fe(II), Yersiniabactin has a weaker affinity to the metal. Why does this happen? (Soft acid-base theory)

Answer 1

a) Siderophores are low molecular mass compounds with high affinities for ferric iron that are secreted into the environment, where they bind precipitated iron or remove it from host binding proteins. Uptake of the iron-siderophore complex provides the bacterial cell with the iron needed for growth. The siderophore dependent iron transport system is known as the yersiniabactin (Ybt) system. Ybt from Y. pestis is identical to that from Y. enterocolitica and has a high affinity for ferric iron. Purified Ybt enhances iron uptake and expression of the psn gene that encodes the outer membrane (OM) receptor for Ybt.

b) The development of the bubonic plague is known to be due to the siderophore-dependent Ybt iron transport system. It is observed that spontaneous Y.pestis nonpigmented mutants (Pgm^-; unable to bind hemin at room temperature) were avirulent in mice via subcutaneous injection unless supplemented with iron or hemin. This mutant was likely a spontaneous deletion of the 102-kb pigmentation (pgm) locus that includes the High Pathogenicity Island (HPI) that encodes genes of the Ybt system. It is proposed that Y.pestis produces siderophores (which is called siderochromes). Pgm⁺ populations of Y.pestis had more siderophore producers than Pgm^-populations and the secreted siderophore inhibited the activity of the bacteriocin pesticin. Only Pgm⁺ cells of Y.pestisare sensitive to pesticin, a bacteriocin produced by Y.pestis whose activity is repressed by growth with iron or hemin. It was subsequently shown that the outer membrane (OM) receptor for pesticin (designated Psn in Y.pestis or FyuA in Y.enterocolitica) mapped to the pgm locus in Y.pestisand serves as the receptor for the Ybt siderophore.

c) 3 OH and 3 Nitrogen

d) Fe²⁺ is soft compared to Fe³⁺ as its charge density is less and its size is bigger than Fe³⁺. But all donors of Yersiniabactin are hard. If Sulphur was the donor then it would have a higher affinity to Fe²⁺ as Sulphur is soft due to bigger size.