J Vet Sci.  2017 Aug;18(S1):343-349. 10.4142/jvs.2017.18.S1.343.

Potential biomarkers as an indicator of vertical transmission of Johne's disease in a Korean native cattle farm

• Park HT
• Park HE
• Cho YI
• Kim EH
• Jung M
• Shin SW
• Lee SH
• Kim DY
• Yoo HS

• KMID: 2412559
• DOI: http://doi.org/10.4142/jvs.2017.18.S1.343

Abstract

Paratuberculosis (PTB) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is one of the most widespread and economically important diseases in cattle. After birth, calves are raised with natural breast feeding without separation from their mothers in most Korean native cattle (Hanwoo breed) farms. Vertical transmission of PTB has been reported, but the exact PTB infection route has not been revealed in Hanwoo farms. Calves of MAP seropositive dams were tested for MAP presence and MAP antibodies in feces and tissues. MAP was detected in calf tissues by using polymerase chain reaction. Expressions of genes reported to be prognostic biomarkers of MAP infection changed in both calves and cows (p < 0.05). Expression of two genes (HGF and SERPINE1) were significantly decreased in MAP-infected cattle and their offspring (p < 0.01). The results suggest that biomarker gene expression profiles can be useful in detecting early stage MAP infection. Based on the results, complete eradication of MAP may be possible if accurate diagnostic methods to detect infected calves are added to the current PTB eradication strategy, which, because infected individuals are likely to develop into fecal MAP shedders at any time, includes isolation of new born calves and feeding sterilized colostrum.

Keyword

Korean native cattle; Mycobacterium avium subsp. paratuberculosis; biomarker; subclinical infection; vertical transmission

MeSH Terms

Animals
Animals, Newborn/microbiology
Cattle
Cattle Diseases/diagnosis/epidemiology/*transmission
Enzyme-Linked Immunosorbent Assay/veterinary
Female
Genetic Markers/genetics
Infectious Disease Transmission, Vertical/*veterinary
Mycobacterium avium subsp. paratuberculosis/*genetics
Paratuberculosis/diagnosis/epidemiology/*transmission
Prognosis
Republic of Korea/epidemiology
Transcriptome
Genetic Markers

Figure

• 

  Fig. 1 Gene expression profiles of cows and calves infected with Mycobacterium avium subsp. paratuberculosis compared to those of non-infected controls. Expression levels were normalized by using the 2−ΔΔCT method relative to the beta-actin expression level and compared to the control group. Fold changes are presented as log2 ratios. *p < 0.05, **p < 0.01.

Reference

1. Abendaño N, Juste RA, Alonso-Hearn M. Anti-inflammatory and antiapoptotic responses to infection: a common denominator of human and bovine macrophages infected with Mycobacterium avium subsp. paratuberculosis. Biomed Res Int. 2013; 2013:908348.

2. Al-Fakhri N, Chavakis T, Schmidt-Wöll T, Huang B, Cherian SM, Bobryshev YV, Lord RS, Katz N, Preissner KT. Induction of apoptosis in vascular cells by plasminogen activator inhibitor-1 and high molecular weight kininogen correlates with their anti-adhesive properties. Biol Chem. 2003; 384:423–435.

3. Aly SS, Thurmond MC. Evaluation of Mycobacterium avium subsp paratuberculosis infection of dairy cows attributable to infection status of the dam. J Am Vet Med Assoc. 2005; 227:450–454.

4. Britton LE, Cassidy JP, O'Donovan J, Gordon SV, Markey B. Potential application of emerging diagnostic techniques to the diagnosis of bovine Johne's disease (paratuberculosis). Vet J. 2016; 209:32–39.

5. Cha SB, Yoo A, Park HT, Sung KY, Shin MK, Yoo HS. Analysis of transcriptional profiles to discover biomarker candidates in Mycobacterium avium subsp. paratuberculosis-infected macrophages, RAW 264.7. J Microbiol Biotechnol. 2013; 23:1167–1175.

6. Coudriet GM, He J, Trucco M, Mars WM, Piganelli JD. Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases. PLoS One. 2010; 5:e15384.

7. Cousins DV, Whittington R, Marsh I, Masters A, Evans RJ, Kluver P. Mycobacteria distenct from Mycobacterium avium subsp. paratuberculosis isolated from the faeces of ruminants possess IS900-like sequences detectable IS900 polymerase chain reaction: implications for diagnosis. Mol Cell Probes. 1999; 13:431–442.

8. Dargatz DA, Byrum BA, Barber LK, Sweeney RW, Whitlock RH, Shulaw WP, Jacobson RH, Stabel JR. Evaluation of a commercial ELISA for diagnosis of paratuberculosis in cattle. J Am Vet Med Assoc. 2001; 218:1163–1166.

9. De Buck J, Shaykhutdinov R, Barkema HW, Vogel HJ. Metabolomic profiling in cattle experimentally infected with Mycobacterium avium subsp. paratuberculosis. PLoS One. 2014; 9:e111872.

10. de Gonzalo-Calvo D, Kenneweg F, Bang C, Toro R, van der Meer RW, Rijzewijk LJ, Smit JW, Lamb HJ, Llorente-Cortes V, Thum T. Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes. Sci Rep. 2016; 6:37354.

11. Dehnad A, Ravindran R, Subbian S, Khan IH. Development of immune-biomarkers of pulmonary tuberculosis in a rabbit model. Tuberculosis (Edinb). 2016; 101:1–7.

12. Eisenberg SW, Rutten VP, Koets AP. Dam Mycobacterium avium subspecies paratuberculosis (MAP) infection status does not predetermine calves for future shedding when raised in a contaminated environment: a cohort study. Vet Res. 2015; 46:70.

13. Farrell D, Shaughnessy RG, Britton L, MacHugh DE, Markey B, Gordon SV. The identification of circulating MiRNA in bovine serum and their potential as novel biomarkers of early Mycobacterium avium subsp paratuberculosis infection. PLoS One. 2015; 10:e0134310.

14. Furie B, Furie BC. The molecular basis of blood coagulation. Cell. 1988; 53:505–518.

15. Hsieh SC, Tsai CY, Yu CL. Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems. Open Access Rheumatol. 2016; 8:81–91.

16. Irenge LM, Walravens K, Govaerts M, Godfroid J, Rosseels V, Huygen K, Gala JL. Development and validation of a triplex real-time PCR for rapid detection and specific identification of M. avium sub sp. paratuberculosis in faecal samples. Vet Microbiol. 2009; 136:166–172.

17. Kalis CH, Barkema HW, Hesselink JW, van Maanen C, Collins MT. Evaluation of two absorbed enzyme-linked immunosorbent assays and a complement fixation test as replacements for fecal culture in the detection of cows shedding Mycobacterium avium subspecies paratuberculosis. J Vet Diagn Invest. 2002; 14:219–224.

18. Lamont EA, Janagama HK, Ribeiro-Lima J, Vulchanova L, Seth M, Yang M, Kurmi K, Waters WR, Thacker T, Sreevatsan S. Circulating Mycobacterium bovis peptides and host response proteins as biomarkers for unambiguous detection of subclinical infection. J Clin Microbiol. 2014; 52:536–543.

19. Malvisi M, Palazzo F, Morandi N, Lazzari B, Williams JL, Pagnacco G, Minozzi G. Responses of bovine innate immunity to Mycobacterium avium subsp. paratuberculosis infection revealed by changes in gene expression and levels of microRNA. PLoS One. 2016; 11:e0164461.

20. McKenna SL, Keefe GP, Tiwari A, VanLeeuwen J, Barkema HW. Johne's disease in Canada part II: disease impacts, risk factors, and control programs for dairy producers. Can Vet J. 2006; 47:1089–1099.

21. Merkal RS, Thurston JR. Comparison of Mycobacterium paratuberculosis and other mycobacteria, using standard cytochemical tests. Am J Vet Res. 1966; 27:519–521.

22. Molnarfi N, Benkhoucha M, Funakoshi H, Nakamura T, Lalive PH. Hepatocyte growth factor: a regulator of inflammation and autoimmunity. Autoimmun Rev. 2015; 14:293–303.

23. Ott SL, Wells SJ, Wagner BA. Herd-level economic losses associated with Johne's disease on US dairy operations. Prev Vet Med. 1999; 40:179–192.

24. Park HE, Shin MK, Park HT, Jung M, Cho YI, Yoo HS. Gene expression profiles of putative biomarker candidates in Mycobacterium avium subsp. paratuberculosis-infected cattle. Pathog Dis. 2016; 74:ftw022.

25. Park HT, Shin MK, Sung KY, Park HE, Cho YI, Yoo HS. Effective DNA extraction method to improve detection of Mycobacterium avium subsp. paratuberculosis in bovine feces. Korean J Vet Res. 2014; 54:55–57.

26. Pithua P, Godden SM, Wells SJ, Oakes MJ. Efficacy of feeding plasma-derived commercial colostrum replacer for the prevention of transmission of Mycobacterium avium subsp paratuberculosis in Holstein calves. J Am Vet Med Assoc. 2009; 234:1167–1176.

27. Ravva SV, Stanker LH. Real-time quantitative PCR detection of Mycobacterium avium subsp. paratuberculosis and differentiation from other mycobacteria using SYBR Green and TaqMan assays. J Microbiol Methods. 2005; 63:305–317.

28. Shin MK, Park H, Shin SW, Jung M, Lee SH, Kim DY, Yoo HS. Host transcriptional profiles and immunopathologic response following Mycobacterium avium subsp. paratuberculosis infection in mice. PLoS One. 2015; 10:e0138770.

29. Shin MK, Park HT, Shin SW, Jung M, Im YB, Park HE, Cho YI, Yoo HS. Whole-blood gene-expression profiles of cows infected with Mycobacterium avium subsp. paratuberculosis reveal changes in immune response and lipid metabolism. J Microbiol Biotechnol. 2015; 25:255–267.

30. Stabel JR. Pasteurization of colostrum reduces the incidence of paratuberculosis in neonatal dairy calves. J Dairy Sci. 2008; 91:3600–3606.

31. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010; 5:463–466.

32. Sweeney RW. Pathogenesis of paratuberculosis. Vet Clin North Am Food Anim Pract. 2011; 27:537–546. v

33. Sweeney RW. Transmission of paratuberculosis. Vet Clin North Am Food Anim Pract. 1996; 12:305–312.

34. Sweeney RW, Whitlock RH, Buckley CL, Spencer PA. Evaluation of a commercial enzyme-linked immunosorbent assay for the diagnosis of paratuberculosis in dairy cattle. J Vet Diagn Invest. 1995; 7:488–493.

35. Sweeney RW, Whitlock RH, McAdams S, Fyock T. Longitudinal study of ELISA seroreactivity to Mycobacterium avium subsp. paratuberculosis in infected cattle and culture-negative herd mates. J Vet Diagn Invest. 2006; 18:2–6.

36. Sweeney RW, Whitlock RH, Rosenberger AE. Mycobacterium paratuberculosis isolated from fetuses of infected cows not manifesting signs of the disease. Am J Vet Res. 1992; 53:477–480.

37. Tiwari A, VanLeeuwen JA, McKenna SL, Keefe GP, Barkema HW. Johne's disease in Canada part I: clinical symptoms, pathophysiology, diagnosis, and prevalence in dairy herds. Can Vet J. 2006; 47:874–882.

38. Wells SJ, Collins MT, Faaberg KS, Wees C, Tavornpanich S, Petrini KR, Collins JE, Cernicchiaro N, Whitlock RH. Evaluation of a rapid fecal PCR test for detection of Mycobacterium avium subsp. paratuberculosis in dairy cattle. Clin Vaccine Immunol. 2006; 13:1125–1130.

39. Whitlock RH, Wells SJ, Sweeney RW, Van Tiem J. ELISA and fecal culture for paratuberculosis (Johne's disease): sensitivity and specificity of each method. Vet Microbiol. 2000; 77:387–398.

40. Windsor PA, Whittington RJ. Evidence for age susceptibility of cattle to Johne's disease. Vet J. 2010; 184:37–44.