Comparative transcriptomics reveals key gene expression differences between the human and bovine pathogens of the Mycobacterium tuberculosis complex.
Members of the Mycobacterium tuberculosis complex show distinct host preferences, yet the molecular basis for this tropism is unknown. Comparison of the M. tuberculosis and Mycobacterium bovis genome sequences revealed no unique genes in the bovine pathogen per se, indicating that differences in gene expression may play a significant role in host predilection. To define the key gene expression differences between M. tuberculosis and M. bovis we have performed transcriptome analyses of cultures grown under steady-state conditions in a chemostat. This revealed that the human and bovine pathogens show differential expression of genes encoding a range of functions, including cell wall and secreted proteins, transcriptional regulators, PE/PPE proteins, lipid metabolism and toxin-antitoxin pairs. Furthermore, we probed the gene expression response of M. tuberculosis and M. bovis to an acid-shock perturbation which triggered a notably different expression response in the two strains. Through these approaches we have defined a core gene set that shows differential expression between the human and bovine tubercle bacilli, and the biological implications are discussed.
Golby
Paul
P
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Hatch
Kim A
KA
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Bacon
Joanna
J
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Cooney
Rory
R
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Riley
Paul
P
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Allnutt
Jon
J
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Hinds
Jason
J
Bacterial Microarray Group, Department of Cellular and Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
Nunez
Javier
J
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Marsh
Philip D
PD
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Hewinson
R Glyn
RG
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Gordon
Stephen V
SV
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
D000143:Acids / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009163:Mycobacterium bovis / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000143:Acids; D000900:Anti-Bacterial Agents