Global gene regulators (GGR) as vaccine candidates against paratuberculosis
Described herein is a mycobacterium mutant, comprising at least one mutation in at least one gene sequence encoding global gene regulators (GGRs) selected from the group consisting of sigH, sigL, sigE, ECF-1, and mixtures thereof, wherein the GGR gene is at least partially inactivated. Described herein also is a vaccine based on the mutant and a method of differentiating between subjects that have been infected with mycobacterium and subjects that have not been infected with mycobacterium or have been vaccinated with a mycobacterium vaccine.
1. A mycobacterium mutant, wherein the mycobacterium is selected from the group consisting of Mycobacterium avium subspecies paratuberculosis (M. ap) and Mycobacterium bovis ( M. bovis ), comprising at least one mutation in at least one gene sequence selected from the group consisting of sigL and ECF-1, which encode a global gene regulator (GGR), wherein the GGR gene is at least partially inactivated.
2. The mutant of claim 1 , wherein the mycobacterium is M. ap.
3. The mutant of claim 1 , wherein the mycobacterium is M. bovis.
4. A mycobacterium mutant, wherein the mycobacterium is Mycobacterium avium subspecies paratuberculosis (M. ap), comprising at least one mutation in sigL (SEQ ID NO:2), which encodes a global gene regulator (GGR), or a sequence substantially identical to SEQ ID NO:2, wherein the GGR is at least partially inactivated.
5. The mutant of claim 1 , wherein the GGR is M. ap ECF-1 (SEQ ID NO:4) or a sequence substantially identical to SEQ ID NO:4.
6. The mutant of claim 1 , wherein the inactivation is achieved by at least partial deletion of a gene sequence encoding a GGR.
7. The mutant of claim 6 , wherein the inactivation is achieved by a complete deletion of a gene sequence encoding a GGR.
8. The mutant of claim 1 , wherein the inactivation is achieved by at least partial transposon insertion of a gene sequence encoding a GGR.
9. The mutant of claim 8 , wherein the inactivation is achieved by a complete transposon insertion of a gene sequence encoding a GGR.
10. The mutant of claim 1 , wherein the inactivation is achieved using a partial anti-sense construct of a gene sequence encoding a GGR.
11. The mutant of claim 10 , wherein the inactivation is achieved using a complete anti-sense construct of a gene sequence encoding a GGR.
12. An isolated mycobacterial organism comprising a mutation according to claim 1 , wherein the mycobacterium is selected from the group consisting of Mycobacterium avium subspecies paratuberculosis (M. ap) and Mycobacterium bovis ( M. bovis ).
13. A mycobacterium vaccine comprising a mycobacterium mutant according to claim 1 .
14. A mycobacterium vaccine comprising an isolated mycobacterial organism comprising a mycobacterium mutant, wherein the mycobacterium is selected from the group consisting of Mycobacterium avium subspecies paratuberculosis (M. ap) and Mycobacterium bovis ( M. bovis ), comprising at least one mutation in sigL, which encodes a global gene regulator (GGR), wherein the GGR gene is at least partially inactivated.
15. The vaccine of claim 14 , wherein the vaccine is physically inactivated.
16. The vaccine of claim 15 , wherein the vaccine is heat inactivated.
17. The vaccine of claim 14 , wherein the vaccine is chemically inactivated.
18. The vaccine of claim 17 , wherein the vaccine is formaldehyde inactivated.
19. The vaccine of claim 14 , wherein the vaccine is a live attenuated vaccine.