Edinburgh Research Explorer

The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi

Research output: Contribution to journalArticle

  • Raul Miranda-CasoLuengo
  • Garry B. Coulson
  • Aleksandra Miranda-CasoLuengo
  • Jose A. Vazquez-Boland
  • Mary K. Hondalus
  • Wim G. Meijer

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: Copyright © 2012, American Society for Microbiology. All Rights Reserved.

    Final published version, 855 KB, PDF document

http://iai.asm.org/content/80/12/4106
Original languageEnglish
Pages (from-to)4106-4114
Number of pages9
JournalInfection and Immunity
Volume80
Issue number12
DOIs
Publication statusPublished - Dec 2012

Abstract

We previously showed that the facultative intracellular pathogen Rhodococcus equi produces a nondiffusible and catecholate-containing siderophore (rhequibactin) involved in iron acquisition during saprophytic growth. Here, we provide evidence that the rhbABCDE cluster directs the biosynthesis of a hydroxamate siderophore, rhequichelin, that plays a key role in virulence. The rhbC gene encodes a nonribosomal peptide synthetase that is predicted to produce a tetrapeptide consisting of N-5-formyl-N-5-hydroxyornithine, serine, N-5-hydroxyornithine, and N-5-acyl-N-5-hydroxyornithine. The other rhb genes encode putative tailoring enzymes mediating modification of ornithine residues incorporated into the hydroxamate product of RhbC. Transcription of rhbC was upregulated during growth in iron-depleted medium, suggesting that it plays a role in iron acquisition. This was confirmed by deletion of rhbCD, rendering the resulting strain R. equi SID2 unable to grow in the presence of the iron chelator 2,2-dipyridyl. Supernatant of the wild-type strain rescued the phenotype of R. equi SID2. The importance of rhequichelin in virulence was highlighted by the rapid increase in transcription levels of rhbC following infection and the inability of R. equi SID2 to grow within macrophages. Unlike the wild-type strain, R. equi SID2 was unable to replicate in vivo and was rapidly cleared from the lungs of infected mice. Rhequichelin is thus a key virulence-associated factor, although nonpathogenic Rhodococcus species also appear to produce rhequichelin or a structurally closely related compound. Rhequichelin biosynthesis may therefore be considered an example of cooption of a core actinobacterial trait in the evolution of R. equi virulence.

    Research areas

  • ELEMENTAL ANALYSIS, NONRIBOSOMAL PEPTIDE SYNTHETASES, GENE-EXPRESSION, MYCOBACTERIUM-TUBERCULOSIS, PROTEIN-A, ABC TRANSPORTER, SAPROPHYTIC GROWTH, MACROPHAGES, ADENYLATION DOMAINS, IRON

Download statistics

No data available

ID: 8018751