Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut

Abstract

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the pH increases. Thus, our results indicate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to commensal and pathogenic Enterobacteriaceae.

Diisonitrile Lipopeptides Mediate Resistance to Copper Starvation in Pathogenic Mycobacteria

“…There is emerging evidence that pathogens use Zn acquisition systems during infection, through either-the elaboration of Zn-scavenging molecules, transport systems for Zn ( 8 ), or import of host-derived Zn containing molecules ( 9 – 11 ). It was recently shown that yersiniabactin, previously characterized as an iron siderophore, also binds Cu ( 12 , 13 ) and Zn ( 14 ) and that the yersiniabactin system is active during infections ( 12 , 14 – 17 ).…”

Nutritional immunity: the battle for nutrient metals at the host–pathogen interface

“…Specifically, siderophores including pyridine-2,6-bis(thiocarboxylic acid) (PDTC), pyochelin, micacocidin and yersiniabactin bind Zn with high affinity 114 – 120 . In fact, scavenging of Zn by yersiniabactin promotes Enterobactericae colonization in the inflamed gut, illustrating the importance of siderophore-mediated Zn acquisition in host colonization 121 . In addition to Zn-binding siderophores, secreted small molecules, termed ‘zincophores’, have been identified from numerous pathogenic bacteria.…”

Siderophores: a potential role as a diagnostic for invasive fungal disease

“…First, some host cells control microbial growth through nutrient limitation. In addition to iron and zinc sequestration [56], restricted access to other metal ions such as Cu 2+ and Mn 2+ can reduce microbial fitness and growth [57]. Most intracellular bacteria are auxotrophic for purines, pyridines and amino acids, which, coupled with the known metabolic restrictions of immune cells, indicates a link between host cell metabolism and growth limitation of intracellular pathogens [58].…”