Abstract
In Klebsiella pneumoniae, we have previously shown that IscR, an Fe–S cluster-containing transcriptional factor, plays a dual role in controlling capsular polysaccharide biosynthesis and iron-acquisition systems by switching between its holo and apo forms. In this study, the effect of IscR on type 3 fimbriae expression and biofilm formation was investigated. We found that production of the major subunit of type 3 fimbriae, MrkA, was increased in the ΔiscR and iscR3CA strains, a strain expressing a mutant IscR that mimics apo-IscR, at both the translational and transcriptional levels. Based on the fact that type 3 fimbriae expression is the major factor affecting biofilm formation, increased biofilm formation was also found in ΔiscR or iscR3CA, suggesting that holo-IscR represses biofilm formation. However, the repression of type 3 fimbriae expression by IscR is indirect. To further understand the regulatory mechanism of IscR, the effect of IscR on the expression of mrkHIJ, which encodes cyclic di-GMP (c-di-GMP)-related regulatory proteins that control type 3 fimbriae expression, was studied. We found that holo-IscR could directly repress mrkHI transcription, indicating that MrkHI is required for IscR regulation of type 3 fimbriae expression. Finally, deletion of iscR attenuated K. pneumoniae virulence in a peritonitis model of mouse infection, while the absence of the [2Fe–2S] cluster of IscR had no effect on K. pneumoniae virulence during infection. Taken together, our results demonstrate the underlying mechanism of the [2Fe–2S] cluster of IscR in controlling type 3 fimbriae expression and its effect on K. pneumoniae pathogenesis.
Highlights
Iron is essential to most bacteria for growth and reproduction
These results suggest that IscR plays a dual role in the regulation of type 3 fimbriae expression and that the status of the [2Fe– 2S] cluster in IscR is critical for this regulation
We found that type 3 fimbriae expression and biofilm formation were affected by the status of [2Fe–2S] cluster of IscR, playing a critical role in mediating the expression of virulence factors for successful infection
Summary
Iron is essential to most bacteria for growth and reproduction. It plays a key role as a cofactor in the electron transport chain and for various enzymes in the tricarboxylic acid (TCA) cycle and oxygen metabolism (Neilands, 1981). Type 3 fimbriae, which are encoded by the mrkABCDF operon, are often expressed in heavily encapsulated K. pneumoniae isolates and play an important role in biofilm formation (Di Martino et al, 2003; Jagnow and Clegg, 2003; Wu et al, 2012). Immunization of mice with purified type 3 fimbriae confers protection against following challenge with virulent K. pneumoniae (Lavender et al, 2005; Wang et al, 2016). Even though these findings indicate the significance of type 3 fimbriae to the virulence of K. pneumoniae, the regulation of the type 3 fimbrial gene expression in K. pneumoniae still remains largely unknown (Murphy and Clegg, 2012)
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