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Genomic variations associated with attenuation in Mycobacterium avium subsp paratuberculosis vaccine strains

Bull, TJ; Schock, A; Sharp, JM; Greene, M; McKendrick, IJ; Sales, J; Linedale, R; Stevenson, K (2013) Genomic variations associated with attenuation in Mycobacterium avium subsp paratuberculosis vaccine strains. BMC MICROBIOLOGY, 13 (11). ISSN 1471-2180 https://doi.org/10.1186/1471-2180-13-11
SGUL Authors: Bull, Timothy John

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Abstract

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) whole cell vaccines have been widely used tools in the control of Johne's disease in animals despite being unable to provide complete protection. Current vaccine strains derive from stocks created many decades ago; however their genotypes, underlying mechanisms and relative degree of their attenuation are largely unknown. RESULTS: Using mouse virulence studies we confirm that MAP vaccine strains 316 F, II and 2e have diverse but clearly attenuated survival and persistence characteristics compared with wild type strains. Using a pan genomic microarray we characterise the genomic variations in a panel of vaccine strains sourced from stocks spanning over 40 years of maintenance. We describe multiple genomic variations specific for individual vaccine stocks in both deletion (26-32 Kbp) and tandem duplicated (11-40 Kbp) large variable genomic islands and insertion sequence copy numbers. We show individual differences suitable for diagnostic differentiation between vaccine and wild type genotypes and provide evidence for functionality of some of the deleted MAP-specific genes and their possible relation to attenuation. CONCLUSIONS: This study shows how culture environments have influenced MAP genome diversity resulting in large tandem genomic duplications, deletions and transposable element activity. In combination with classical selective systematic subculture this has led to fixation of specific MAP genomic alterations in some vaccine strain lineages which link the resulting attenuated phenotypes with deficiencies in high reactive oxygen species handling.

Item Type: Article
Additional Information: © 2013 Bull et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Animals, Bacterial Vaccines, DNA, Bacterial, Disease Models, Animal, Genetic Variation, Mice, Mice, Inbred C57BL, Microarray Analysis, Mycobacterium avium subsp. paratuberculosis, Paratuberculosis, Survival Analysis, Vaccines, Attenuated, Science & Technology, Life Sciences & Biomedicine, Microbiology, Mycobacterium avium subspecies paratuberculosis, Vaccine, Comparative genomics, Variable genomic island, Attenuation, Microarray, DUTCH DAIRY HERDS, JOHNES-DISEASE, IMMUNE-RESPONSE, CROHNS-DISEASE, TUBERCULOSIS, EFFICACY, GOATS, CATTLE, SHEEP, SENSITIVITY
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: BMC MICROBIOLOGY
ISSN: 1471-2180
Dates:
DateEvent
22 January 2013Published
PubMed ID: 23339684
Web of Science ID: 23339684
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URI: https://openaccess.sgul.ac.uk/id/eprint/101071
Publisher's version: https://doi.org/10.1186/1471-2180-13-11

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