The global regulatory effect of Edwardsiella tarda Fur on iron acquisition, stress resistance, and host infection: A proteomics-based interpretation

• Fur affected the growth, siderophore production, and acid tolerance of E. tarda.
• fur mutation decreased bacterial survival against oxidative stress and host serum.
• fur mutation impaired the ability of E. tarda to inhibit host immune response.
• fur mutation attenuated the overall virulence of E. tarda.
• fur mutation affected the expression of a large amount of proteins.

Ferric uptake regulator (Fur) is an important transcriptional regulator of Gram-negative bacteria. Edwardsiella tarda is a severe fish bacterial pathogen with a broad host range that includes humans. In this study, we examined the regulatory function of Fur in E. tarda via a proteomic approach. Compared to the wild type TX01, the fur mutant TX01Δfur exhibited (i) retarded growth, (ii) enhanced siderophore production, (iii) increased acid tolerance, which is in contrast to observations in other bacterial species, (iv) decreased survival against oxidative stress and host serum, (v) impaired ability to inhibit host immune response, (vi) attenuated tissue infectivity and overall virulence. The deficiency of TX01Δfur was rescued by introduction of an exogenous fur gene. iTRAQ-based comparative proteomic analysis of TX01Δfur and TX01 identified 89 differentially expressed proteins that cover a wide range of functional categories including those affected by fur mutation. In addition, 16 proteins were identified for the first time to be regulated by Fur in Gram-negative bacteria. These results provide the first protein-based interpretation of the global impact of Fur on the physiology and infectivity of E. tarda.SignificanceThis study demonstrates that in E. tarda, Fur controls multiple aspects of bacterial life, including growth, metabolism, iron acquisition, stress response, and host infection. In line with these observations, proteomics analysis identified a large amount of proteins affected in expression by Fur, which are involved in bacterial physiology and infectivity. Hence, these results link for the first time the pleiotropic effect of Fur with global protein expression and shed new light on the function and regulatory mechanism of Fur in pathogenic bacteria.

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