Mycobacterium bovis BCG vaccine strains lack narK2 and narX induction and exhibit altered phenotypes during dormancy.
Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world's population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T cells of M. tuberculosis-infected individuals, especially those harboring latent infections. Differences in the expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for the induction of two dormancy genes: narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains.
Honaker
Ryan W
RW
University of Colorado Denver, School of Medicine, Department of Microbiology, P18-9115, 12800 East 19th Avenue, P.O. Box 6511, Aurora, CO 80045, USA.
Stewart
Amanda
A
Schittone
Stephanie
S
Izzo
Angelo
A
Klein
Michèl R
MR
Voskuil
Martin I
MI
D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D001500:BCG Vaccine; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D009163:Mycobacterium bovis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D000091285:Nitrate Transporters; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D018085:Regulon / Q000235:genetics / Q000502:physiology
D027321:Anion Transport Proteins; D001500:BCG Vaccine; D001426:Bacterial Proteins; D000091285:Nitrate Transporters