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HorseAdvice.com » Diseases of Horses » Respiratory System » Foal Pneumonia: Rhodococcus » |
Discussion on Research Summary: Possible Vaccine for Rhodococcus? | |
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Moderator: DrO |
Posted on Saturday, Sep 17, 2011 - 9:59 am: It has been recently reported that much of the virulence of the foal pneumonia organism, Rhodococcus equi, is related to a cholesterol catabolic enzyme. Along with identification of the location of the gene that encodes this information is the realization that some mutations of this organism lack this gene. This should impair the ability of the organism to create disease yet may be able to confer immunity to those exposed to it.Though not commercially available this shows great promise to end what is still for some breeding farms a difficult and expensive problem year after year. DrO PLoS Pathog. 2011 Aug;7(8):e1002181. The Steroid Catabolic Pathway of the Intracellular Pathogen Rhodococcus equi Is Important for Pathogenesis and a Target for Vaccine Development. van der Geize R, Grommen AW, Hessels GI, Jacobs AA, Dijkhuizen L. Source Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Microbiology, University of Groningen, Groningen, The Netherlands. Abstract Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and immunocompromised animals and humans. Despite its importance, there is currently no effective vaccine against the disease. The actinobacteria R. equi and the human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary diseases. Recently, we have shown that essential steps in the cholesterol catabolic pathway are involved in the pathogenicity of M. tuberculosis. Bioinformatic analysis revealed the presence of a similar cholesterol catabolic gene cluster in R. equi. Orthologs of predicted M. tuberculosis virulence genes located within this cluster, i.e. ipdA (rv3551), ipdB (rv3552), fadA6 and fadE30, were identified in R. equi RE1 and inactivated. The ipdA and ipdB genes of R. equi RE1 appear to constitute the α-subunit and β-subunit, respectively, of a heterodimeric coenzyme A transferase. Mutant strains RE1ΔipdAB and RE1ΔfadE30, but not RE1ΔfadA6, were impaired in growth on the steroid catabolic pathway intermediates 4-anDrOstene-3,17-dione (AD) and 3aα-H-4α(3'-propionic acid)-5α-hyDrOxy-7aβ-methylhexahyDrO-1-indanone (5α-hyDrOxy-methylhexahyDrO-1-indanone propionate; 5OH-HIP). Interestingly, RE1ΔipdAB and RE1ΔfadE30, but not RE1ΔfadA6, also displayed an attenuated phenotype in a macrophage infection assay. Gene products important for growth on 5OH-HIP, as part of the steroid catabolic pathway, thus appear to act as factors involved in the pathogenicity of R. equi. Challenge experiments showed that RE1ΔipdAB could be safely administered intratracheally to 2 to 5 week-old foals and oral immunization of foals even elicited a substantial protective immunity against a virulent R. equi strain. Our data show that genes involved in steroid catabolism are promising targets for the development of a live-attenuated vaccine against R. equi infections |
Member: mrose |
Posted on Saturday, Sep 17, 2011 - 11:36 am: Interesting stuff! It would be such a boon to the horse industry to have a vaccine. R.equi can be devistating to deal with. Thanks for posting. |