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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02436

FNR-dependent RmpA and RmpA2 regulation of capsule polysaccharide biosynthesis in Klebsiella pneumoniae

  • 1School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Taiwan
  • 2Department of Urology, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taiwan
  • 3Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taiwan
  • 4Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taiwan
  • 5National Yang-Ming University, Taiwan
  • 6China University of Science and Technology, Taiwan
  • 7School of Chinese Medicine, China Medical University, Taiwan

Fumarate nitrate reduction regulator (FNR) is a direct oxygen-responsive transcriptional regulator containing an iron-sulfur (Fe-S) cluster. During anaerobic growth, the [4Fe-4S] cluster in FNR (holo-FNR) binds specifically to DNA, whereas exposure to oxygen results in the loss of its DNA-binding activity via oxidation of the [4Fe-4S] cluster. In this study, we aimed to investigate the role of FNR in regulation of capsular polysaccharide (CPS) biosynthesis, serum resistance, and anti-phagocytosis of K. pneumoniae. We found that the CPS amount in K. pneumoniae increased in anaerobic conditions, compared to that in aerobic conditions. An fnr deletion mutant and a site-directed mutant (fnr3CA), with the three cysteines (C20, C23, and C29) replaced with alanines to mimic an FNR lacking the [4Fe-4S] cluster, showed marked increase in CPS amount under anaerobic conditions. A promoter-reporter assay and qRT-PCR confirmed that the transcription of the cps genes was repressed by holo-FNR. In addition, we found that holo-FNR could repress the transcription of rmpA and rmpA2, encoding cps transcriptional activators. Deletion of rmpA or rmpA2 in the fnr strain reduced CPS biosynthesis, suggesting that RmpA and RmpA2 participated in the holo-FNR–mediated repression of cps transcription, thereby regulating the CPS amount, serum resistance, and anti-phagocytosis. Taken together, our results provided evidence that RmpA and RmpA2 participated in the holo-FNR–mediated repression of CPS biosynthesis, and resistance to the host defense in response to oxygen availability.

Keywords: Klebsiella pneumoniae, Oxygen, FNR, Capsule polysaccharide, RmpA, rmpA2

Received: 15 Apr 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Lin, Wu, Kuo, Chu, Lee and LIN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. CHING-TING LIN, China Medical University, School of Chinese Medicine, Taichung City, 40402, Taichung County, Taiwan, gingting@mail.cmu.edu.tw