Iron is an essential nutrient for bacterial life but is restricted in the host, with the consequence that most human pathogens produce specific iron acquisition proteins or molecules in order to facilitate infection. Siderophores are small high-affinity iron chelators produced by many pathogens. All Klebsiella pneumoniae strains produce the siderophore enterobactin, while hypervirulent strains produce up to three additional siderophores; salmochelin, yersiniabactin and aerobactin. Even though these systems all have the same supposed function – acquiring iron – the production of additional siderophore types is strongly predictive of hypervirulence. In this study, we have examined siderophore expression and maintenance in K. pneumoniae to gain insight into how these distinct acquisition systems are coordinated during infection.
We found that all four siderophores are subject to differential regulation based on severity of iron starvation together with other cues. The four siderophores show distinct expression patterns within the host during infection, and are controlled by additional regulators beyond the iron master regulator Fur. Genomic analysis indicated that loss of the ability to produce, but not use, particular siderophores is a reasonably common in Klebsiella pneumoniae isolates. Overall our results support a view of the four Klebsiella pneumoniae siderophores as non-redundant entities offering distinct adaptive advantages, and subject to diversifying selection due to host factors and competitive microbe-microbe interactions.