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

BMC Microbiology

Karen Stevenson⁵  Richard Linedale³  Jill Sales⁴  Iain J McKendrick⁴  Mandisa Greene²  J Michael Sharp¹  Alex Schock¹  Tim J Bull³ 

[1]AHVLA Lasswade, Bush Loan, EH26 0PZ, Penicuik, Midlothian, UK

[2]Present address: Charter Veterinary Surgeons, 51 Congleton Road, ST8 6EF, Stoke On Trent, UK

[3]St. George’s University of London Medical School, SW17 0RE, London, UK

[4]Biomathematics & Statistics Scotland, James Clerk Maxwell Building, The King’s Buildings, Mayfield Road, EH9 3JZ, Edinburgh, UK

[5]Moredun Research Institute, Bush Loan, EH26 0PZ, Penicuik, Midlothian, UK

关键词: Microarray;    Attenuation;    Variable genomic island;    Comparative genomics;    Vaccine;    Mycobacterium avium subspecies paratuberculosis;   

Others  :  1144603
DOI  :  10.1186/1471-2180-13-11

 received in 2012-07-19, accepted in 2013-01-11,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Bull et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Hutchings MR, Stevenson K, Greig A, Davidson RS, Marion G, Judge J: Infection of Non-ruminant Wildlife by Mycobacterium avium subsp.paratuberculosis. In Paratuberculosis; Organism, Disease, Control. Edited by Behr MA, Collins DM. Wallingford: CAB International; 2010:188-200.
• [2]Raizman EA, Fetrow JP, Wells SJ: Loss of income from cows shedding mycobacterium avium subspecies paratuberculosis prior to calving compared with cows not shedding the organism on two Minnesota dairy farms. J Dairy Sci 2009, 92:4929-4936.
• [3]Behr MA, Kapur V: The evidence for mycobacterium paratuberculosis in Crohn’s disease. Curr Opin Gastroenterol 2008, 24:17-21.
• [4]van Schaik G, Kalis CH, Benedictus G, Dijkhuizen AA, Huirne RB: Cost-benefit analysis of vaccination against paratuberculosis in dairy cattle. Vet Rec 1996, 139:624-627.
• [5]Muskens J, Elbers AR, van Weering HJ, Noordhuizen JP: Herd management practices associated with paratuberculosis seroprevalence in Dutch dairy herds. J Vet Med B Infect Dis Vet Public Health 2003, 50:372-377.
• [6]Kudahl AB, Sorensen JT, Nielsen SS, Ostergaard S: Simulated economic effects of improving the sensitivity of a diagnostic test in paratuberculosis control. Prev Vet Med 2007, 78:118-129.
• [7]Hines ME, Stiver S, Giri D, Whittington L, Watson C, Johnson J: Efficacy of spheroplastic and cell-wall competent vaccines for Mycobacterium avium subsp. paratuberculosis in experimentally-challenged baby goats. Vet Microbiol 2007, 120:261-283.
• [8]Emery DL, Whittington RJ: An evaluation of mycophage therapy, chemotherapy and vaccination for control of Mycobacterium avium subsp. paratuberculosis infection. Vet Microbiol 2004, 104:143-155.
• [9]Juste RA, Alonso-Hearn M, Molina E, Geijo M, Vazquez P, Sevilla IA: Significant reduction in bacterial shedding and improvement in milk production in dairy farms after the use of a new inactivated paratuberculosis vaccine in a field trial. BMC Res Notes 2009, 2:233. BioMed Central Full Text
• [10]Pickup RW, Rhodes G, Arnott S, Sidi-Boumedine K, Bull TJ, Weightman A: Mycobacterium avium subsp. paratuberculosis in the catchment area and water of the River Taff in South Wales, United Kingdom, and its potential relationship to clustering of Crohn’s disease cases in the city of Cardiff. Appl Environ Microbiol 2005, 71:2130-2139.
• [11]Rosseels V, Huygen K: Vaccination against paratuberculosis. Expert Rev Vaccines 2008, 7:817-832.
• [12]Singh SV, Singh PK, Singh AV, Sohal JS, Gupta VK, Vihan VS: Comparative efficacy of an indigenous ’inactivated vaccine’ using highly pathogenic field strain of Mycobacterium avium subspecies paratuberculosis ‘Bison type’ with a commercial vaccine for the control of Capri-paratuberculosis in India. Vaccine 2007, 25:7102-7110.
• [13]Kozak R, Behr MA: Divergence of immunologic and protective responses of different BCG strains in a murine model. Vaccine 2011, 29:1519-1526.
• [14]Doyle TM: Strains of Mycobacterium johnei used for the preparation of vaccine. State Veterinary Journal 1964, 19–20:154-155.
• [15]Saxegaard F, Fodstad FH: Control of paratuberculosis (Johne’s disease) in goats by vaccination. Vet Rec 1985, 116:439-441.
• [16]Sigurdsson B, Tryggvadottir AG: Immunization with heat-killed Mycobacterium paratuberculosis in mineral oil. J Bacteriol 1950, 59:541-543.
• [17]Wilesmith JW: Johne’s disease: a retrospective study of vaccinated herds in Great Britain. Br Vet J 1982, 138:321-331.
• [18]Crowther RW, Polydorou K, Nitti S, Phyrilla A: Johne’s disease in sheep in Cyprus. Vet Rec 1976, 98:463.
• [19]Kormendy B: The effect of vaccination on the prevalence of paratuberculosis in large dairy herds. Vet Microbiol 1994, 41:117-125.
• [20]Klawonn W, Cussler K, Drager KG, Gyra H, Kohler H, Zimmer K: [The importance of allergic skin test with Johnin, antibody ELISA, cultural fecal test as well as vaccination for the sanitation of three chronically paratuberculosis-infected dairy herds in Rhineland-Palatinate]. Dtsch Tierarztl Wochenschr 2002, 109:510-516.
• [21]Molina JM, Anguiano A, Ferrer O: Study on immune response of goats vaccinated with a live strain of Mycobacterium paratuberculosis. Comp Immunol Microbiol Infect Dis 1996, 19:9-15.
• [22]Begg DJ, Griffin JF: Vaccination of sheep against M. paratuberculosis: immune parameters and protective efficacy. Vaccine 2005, 23:4999-5008.
• [23]Reddacliff L, Eppleston J, Windsor P, Whittington R, Jones S: Efficacy of a killed vaccine for the control of paratuberculosis in Australian sheep flocks. Vet Microbiol 2006, 115:77-90.
• [24]Thorel MF: Review of the occurrence of mycobactin dependence among mycobacteria species. Ann Rech Vet 1984, 15:405-409.
• [25]Thibault VC, Grayon M, Boschiroli ML, Hubbans C, Overduin P, Stevenson K: New variable-number tandem-repeat markers for typing Mycobacterium avium subsp. paratuberculosis and M. avium strains: comparison with IS900 and IS1245 restriction fragment length polymorphism typing. J Clin Microbiol 2007, 45:2404-2410.
• [26]Castellanos E, Aranaz A, Gould KA, Linedale R, Stevenson K, Alvarez J: Discovery of sand variable differences in the Mycobacterium avium subsp. paratuberculosis type I, II, and III genomes by pan-genome microarray analysis. Appl Environ Microbiol 2009, 75:676-686.
• [27]Taylor DE: Bacterial tellurite resistance. Trends Microbiol 1999, 7:111-115.
• [28]Chasteen TG, Fuentes DE, Tantalean JC, Vasquez CC: Tellurite: history, oxidative stress, and molecular mechanisms of resistance. FEMS Microbiol Rev 2009, 33:820-832.
• [29]Watkins C, Schock A, May L, Denham S, Sales J, Welch L: Assessing virulence of vaccine strains of Mycobacterium avium subspecies paratuberculosis in a calf model. Vet Microbiol 2010, 146:63-69.
• [30]Stratmann J, Strommenger B, Goethe R, Dohmann K, Gerlach GF, Stevenson K: A 38-kilobase pathogenicity island specific for Mycobacterium avium subsp. paratuberculosis encodes cell surface proteins expressed in the host. Infect Immun 2004, 72:1265-1274.
• [31]Paustian ML, Amonsin A, Kapur V, Bannantine JP: Characterization of novel coding sequences specific to mycobacterium avium subsp. Paratuberculosis: implications for diagnosis of Johne’s disease. J Clin Microbiol 2004, 42:2675-2681.
• [32]Beste DJ, Bonde B, Hawkins N, Ward JL, Beale MH, Noack S: (1)(3)C metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation. PLoS Pathog 2011, 7:e1002091.
• [33]Wayne LG, Lin KY: Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect Immun 1982, 37:1042-1049.
• [34]McKinney JD, BK Hz, Munoz-Elias EJ, Miczak A, Chen B, Chan WT: Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000, 406:735-738.
• [35]Hasvold HJ, Valheim M, Berntsen G, Storset AK: In vitro responses to purified protein derivate of caprine T lymphocytes following vaccination with live strains of Mycobacterium avium subsp paratuberculosis. Vet Immunol Immunopathol 2002, 90:79-89.
• [36]Cooper WC: Tellurium. New York: Van Nostrand Reinhold; 1971.
• [37]Calderon IL, Arenas FA, Perez JM, Fuentes DE, Araya MA, Saavedra CP: Catalases are NAD(P)H-dependent tellurite reductases. PLoS One 2006, 1:e70.
• [38]Muskens J, van ZF, Eger A, Bakker D: Evaluation of the long-term immune response in cattle after vaccination against paratuberculosis in two Dutch dairy herds. Vet Microbiol 2002, 86:269-278.
• [39]Wynne JW, Bull TJ, Seemann T, Bulach DM, Wagner J, Kirkwood CD: Exploring the zoonotic potential of Mycobacterium avium subspecies paratuberculosis through comparative genomics. PLoS One 2011, 6:e22171.
• [40]Bull TJ, Hermon-Taylor J, Pavlik I, El-Zaatari F, Tizard M: Characterization of IS900 loci in Mycobacterium avium subsp. paratuberculosis and development of multiplex PCR typing. Microbiology 2000, 146(Pt 9):2185-2197.
• [41]Eamens GJ, Whittington RJ, Marsh IB, Turner MJ, Saunders V, Kemsley PD: Comparative sensitivity of various faecal culture methods and ELISA in dairy cattle herds with endemic Johne’s disease. Vet Microbiol 2000, 77:357-367.
• [42]Collins DM, Gabric DM, de Lisle GW: Identification of two groups of Mycobacterium paratuberculosis strains by restriction endonuclease analysis and DNA hybridization. J Clin Microbiol 1990, 28:1591-1596.
• [43]Mahillon J, Chandler M: Insertion sequences. Microbiol Mol Biol Rev 1998, 62:725-774.
• [44]Klanicova B, Slana I, Vondruskova H, Kaevska M, Pavlik I: Real-time quantitative PCR detection of Mycobacterium avium subspecies in meat products. J Food Prot 2011, 74:636-640.
• [45]Roberts G, Vadrevu IS, Madiraju MV, Parish T: Control of CydB and GltA1 expression by the SenX3 RegX3 two component regulatory system of Mycobacterium tuberculosis. PLoS One 2011, 6:e21090.
• [46]Magdalena J, Supply P, Locht C: Specific differentiation between Mycobacterium bovis BCG and virulent strains of the Mycobacterium tuberculosis complex. J Clin Microbiol 1998, 36:2471-2476.
• [47]Saxegaard F: Isolation of Mycobacterium paratuberculosis from intestinal mesenteric lymph nodes of goats by use of selective Dubos medium. J Clin Microbiol 1985, 22:312-313.
• [48]Cousins DV, Gabric DM, deLisle GW: Identification of two groups of Mycobacterium paratuberculosis strains by restriction endonuclease analysis and DNA hybridisation. J Clin Microbiol 1990, 28:1591-1596.
• [49]Bull TJ, Sidi-Boumedine K, McMinn EJ, Stevenson K, Pickup R, Hermon-Taylor J: Mycobacterial interspersed repetitive units (MIRU) differentiate Mycobacterium avium subspecies paratuberculosis from other species of the Mycobacterium avium complex. Mol Cell Probes 2003, 17:157-164.
• [50]Dorrell N, Mangan JA, Laing KG, Hinds J, Linton D, Al-Ghusein H: Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity. Genome Res 2001, 11:1706-1715.
• [51]Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 1998, 95:14863-14868.
• [52]Beard PM, Stevenson K, Pirie A, Rudge K, Buxton D, Rhind SM: Experimental paratuberculosis in calves following inoculation with a rabbit isolate of Mycobacterium avium subsp. paratuberculosis. J Clin Microbiol 2001, 39:3080-3084.