Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

No abstract

We report the genome of the facultative intracellular parasite Rhodococcus equi, the only animal pathogen within the biotechnologically important actinobacterial genus Rhodococcus. The 5.0-Mb R. equi 103S genome is significantly smaller than those of environmental rhodococci. This is due to genome expansion in nonpathogenic species, via a linear gain of paralogous genes and an accelerated genetic flux, rather than reductive evolution in R. equi. The 103S genome lacks the extensive catabolic and secondary metabolic complement of environmental rhodococci, and it displays unique adaptations for host colonization and competition in the short-chain fatty acid–rich intestine and manure of herbivores—two main R. equi reservoirs. Except for a few horizontally acquired (HGT) pathogenicity loci, including a cytoadhesive pilus determinant (rpl) and the virulence plasmid vap pathogenicity island (PAI) required for intramacrophage survival, most of the potential virulence-associated genes identified in R. equi are conserved in environmental rhodococci or have homologs in nonpathogenic Actinobacteria. This suggests a mechanism of virulence evolution based on the cooption of existing core actinobacterial traits, triggered by key host niche–adaptive HGT events. We tested this hypothesis by investigating R. equi virulence plasmid-chromosome crosstalk, by global transcription profiling and expression network analysis. Two chromosomal genes conserved in environmental rhodococci, encoding putative chorismate mutase and anthranilate synthase enzymes involved in aromatic amino acid biosynthesis, were strongly coregulated with vap PAI virulence genes and required for optimal proliferation in macrophages. The regulatory integration of chromosomal metabolic genes under the control of the HGT–acquired plasmid PAI is thus an important element in the cooptive virulence of R. equi.

The pathogenic actinomycete Rhodococcus equi harbors different types of virulence plasmids associated with specific nonhuman hosts. We determined the complete DNA sequence of a vapB ؉ plasmid, typically associated with pig isolates, and compared it with that of the horse-specific vapA ؉ plasmid type. pVAPB1593, a circular 79,251-bp element, had the same housekeeping backbone as the vapA ؉ plasmid but differed over an Ϸ22-kb region. This variable region encompassed the vap pathogenicity island (PAI), was clearly subject to selective pressures different from those affecting the backbone, and showed major genetic rearrangements involving the vap genes. The pVAPB1593 PAI harbored five different vap genes (vapB and vapJ to -M, with vapK present in two copies), which encoded products differing by 24 to 84% in amino acid sequence from the six full-length vapA ؉ plasmid-encoded Vap proteins, consistent with a role for the specific vap gene complement in R. equi host tropism. Sequence analyses, including interpolated variable-order motifs for detection of alien DNA and reconstruction of Vap family phylogenetic relationships, suggested that the vap PAI was acquired by an ancestor plasmid via lateral gene transfer, subsequently evolving by vap gene duplication and sequence diversification to give different (host-adapted) plasmids. The R. equi virulence plasmids belong to a new family of actinobacterial circular replicons characterized by an ancient conjugative backbone and a horizontally acquired niche-adaptive plasticity region.Rhodococcus equi is a member of the mycolic acid-containing group of actinobacteria, or mycolata, which also includes the Corynebacterium, Gordonia, Mycobacterium, and Nocardia genera (18). Like many other actinomycetes, R. equi is ubiquitous in nature and lives as a saprophyte in soil (25,35,41). The genus Rhodococcus is a genetically diverse taxon that may be empirically classified into two groups (4, 23): the nonpathogenic, or environmental, rhodococci, exemplified by Rhodococcus erythropolis, which includes metabolically versatile bacteria of industrial interest (32), and the pathogenic rhodococci, with two species, the plant pathogen Rhodococcus fascians (22) and the animal pathogen R. equi (25,35,41). All rhodococci typically harbor large conjugative plasmids encoding nicheadaptive functions, such as various primary and secondary metabolic processes in the environmental species and host colonization (virulence) factors in the pathogenic ones. Some of these extrachromosomal replicons are linear megaplasmids of up to 1 Mb in size, whereas others are circular plasmids of Ϸ100 kb (34, 55).R. equi can be isolated from pulmonary and extrapulmonary pyogranulomatous infections in various mammalian hosts. It causes equine purulent bronchopneumonia, or rattles, a severe respiratory disease of foals characterized by extensive abscessation of the lung parenchyma, lymphadenitis, and a high mortality rate. R. equi is also an opportunistic human pathogen associated with AIDS and immunosuppression. Human rho...

Infection with Rhodococcus (Corynebacterium) equi is a well-recognised condition in foals that represents a consistent and serious risk worldwide. The condition manifests itself primarily as one of pulmonary abscessation and bronchitis, hence the terminology of 'rattles' derived from its most obvious clinical sign, frequently terminal when first identified. This review addresses the clinical manifestation, bacteriology and pathogenesis of the condition together with recent developments providing knowledge of the organism in terms of virulence, epidemiology, transmission and immune responses. Enhanced understanding of R. equi virulence mechanisms and biology derived from the recently available genome sequence may facilitate the rational development of a vaccine and the improvement of farm management practices used to control R. equi on stud farms in the future. Reliance on vaccines alone, in the absence of management strategies to control the on-farm challenge is likely to be disappointing.