Comparative Genomics of Rhodococcus equi Virulence Plasmids Indicates Host-Driven Evolution of the vap Pathogenicity Island

Abstract

The conjugative virulence plasmid is a key component of the Rhodococcus equi accessory genome essential for pathogenesis. Three host-associated virulence plasmid types have been identified: the equine pVAPA and porcine pVAPB circular variants, and the linear pVAPN found in bovine (ruminant) isolates. We recently characterized the R. equi pangenome (Anastasi E, et al. 2016. Pangenome and phylogenomic analysis of the pathogenic actinobacterium Rhodococcus equi. Genome Biol Evol. 8:3140–3148.) and we report here the comparative analysis of the virulence plasmid genomes. Plasmids within each host-associated type were highly similar despite their diverse origins. Variation was accounted for by scattered single nucleotide polymorphisms and short nucleotide indels, while larger indels—mostly in the plasticity region near the vap pathogencity island (PAI)—defined plasmid genomic subtypes. Only one of the plasmids analyzed, of pVAPN type, was exceptionally divergent due to accumulation of indels in the housekeeping backbone. Each host-associated plasmid type carried a unique PAI differing in vap gene complement, suggesting animal host-specific evolution of the vap multigene family. Complete conservation of the vap PAI was observed within each host-associated plasmid type. Both diversity of host-associated plasmid types and clonality of specific chromosomal-plasmid genomic type combinations were observed within the same R. equi phylogenomic subclade. Our data indicate that the overall strong conservation of the R. equi host-associated virulence plasmids is the combined result of host-driven selection, lateral transfer between strains, and geographical spread due to international livestock exchanges.

Novel bovine-associated pVAPN plasmid type in Rhodococcus equi identified from lymph nodes of slaughtered cattle and lungs of people living with HIV/AIDS

“…Currently, three host‐adapted virulence plasmid types are recognized, the circular pVAPA and pVAPB (MacArthur, Anastasi, Alvarez, Scortti, & Vázquez‐Boland, ), and a recently identified linear pVAPN type (Valero‐Rello et al., ). pVAPA and pVAPB types are associated, respectively, with equine and porcine strains (MacArthur et al., ; Valero‐Rello et al., ; Vázquez‐Boland et al., ).…”

“…Currently, three host‐adapted virulence plasmid types are recognized, the circular pVAPA and pVAPB (MacArthur, Anastasi, Alvarez, Scortti, & Vázquez‐Boland, ), and a recently identified linear pVAPN type (Valero‐Rello et al., ). pVAPA and pVAPB types are associated, respectively, with equine and porcine strains (MacArthur et al., ; Valero‐Rello et al., ; Vázquez‐Boland et al., ). Most equine type (pVAPA) are found in R. equi associated with typical life‐threatening pyogranulomatous pneumonia and ulcerative colitis in foals (Meijer & Prescott, ), whereas porcine type (pVAPB) is predominantly carried by isolates recovered from the lymph nodes of pigs, wild boars (Ribeiro, Lara et al., ) and humans, particularly immunocompromised patients (Makrai et al., ; Ribeiro, Takai et al., ; Takai et al., ).…”

Conservation of Rhodococcus equi (Magnusson 1923) Goodfellow and Alderson 1977 and rejection of Rhodococcus hoagii (Morse 1912) Kämpfer et al. 2014

“…Note the dominant solid pink sequence segments which denote near complete conservation between the genomes, consistent with the high degree of genomic relatedness between R. equi (hoagii) isolates [13]. be linked to a specific R. equi genomic type but to be horizontally exchangeable across the species' population structure (associated with corresponding host jumps) [13,29]. In addition, the three plasmid types can also be indistinctly found in isolates recovered from non-adapted (opportunistic) animal hosts (e.g.…”

“…In contrast, the equi epithet has been in widespread use and constantly associated with its cognate bacterial species since its discovery in 1923 by H. Magnusson as the causative agent of a severe infectious disease of foals [26,27]. While R. equi can also cause opportunistic human infections and colonize other animal species [14,17,18,[28][29][30], it remains best known as a major horse pathogen and thus the epithet is aptly descriptive of the species [31,32]. Indeed, the name R. equi has a solid standing in veterinary and human medicine, animal science and the equine industry, and the change to R. hoagii is disconcerting and likely to hamper the traceability and interpretation of the medical, scientific and technical literature regarding this pathogen.…”

“…Hoag found it 'a number of times' in throat cultures [21] and Morse refers to these diphtheroids as being the most abundant among the human throat isolates she examined [22]. However, R. equi is not known to be a human commensal, only rarely infects people and, when found in human specimens, it is almost invariably associated with severe invasive infections (of suspected exogenous acquisition via exposure to livestock farming environments) [18,29].…”