Journal
INFECTION AND IMMUNITY
Volume 83, Issue 7, Pages 2725-2737Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00376-15
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Funding
- Horserace Betting Levy Board [vet/prj/712, vet/prj/753]
- Research Stimulus Fund [RSF 06 379]
- core BBSRC from Roslin Institute
- European Union Marie Curie postdoctoral fellowship
- BBSRC from Centre for Infectious Diseases of University of Edinburgh (UoE)
- Zoetis
- UoE
- BBSRC [BBS/E/D/20310000, BBS/E/D/20231761] Funding Source: UKRI
- MRC [G0900740, MR/K001744/1] Funding Source: UKRI
- NERC [NBAF010003] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/D/20310000, 1136001, BBS/E/D/20231761] Funding Source: researchfish
- Medical Research Council [G0900740, MR/K001744/1] Funding Source: researchfish
- Natural Environment Research Council [NBAF010003] Funding Source: researchfish
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We report a novel host-associated virulence plasmid in Rhodococcus equi, pVAPN, carried by bovine isolates of this facultative intracellular pathogenic actinomycete. Surprisingly, pVAPN is a 120-kb invertron-like linear replicon unrelated to the circular virulence plasmids associated with equine (pVAPA) and porcine (pVAPB variant) Rhodococcus equi isolates. pVAPN is similar to the linear plasmid pNSL1 from Rhodococcus sp. NS1 and harbors six new vap multigene family members (vapN to vapS) in a vap pathogenicity locus presumably acquired via en bloc mobilization from a direct predecessor of equine pVAPA. Loss of pVAPN rendered Rhodococcus equi avirulent in macrophages and mice. Mating experiments using an in vivo transconjugant selection strategy demonstrated that pVAPN transfer is sufficient to confer virulence to a plasmid-cured Rhodococcus equi recipient. Phylogenetic analyses assigned the vap multigene family complement from pVAPN, pVAPA, and pVAPB to seven monophyletic clades, each containing plasmid type-specific allelic variants of a precursor vap gene carried by the nearest vap island ancestor. Deletion of vapN, the predicted bovine-type allelic counterpart of vapA, essential for virulence in pVAPA, abrogated pVAPN-mediated intramacrophage proliferation and virulence in mice. Our findings support a model in which Rhodococcus equi virulence is conferred by host-adapted plasmids. Their central role is mediating intracellular proliferation in macrophages, promoted by a key vap determinant present in the common ancestor of the plasmid-specific vap islands, with host tropism as a secondary trait selected during coevolution with specific animal species.
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