Comparative transcriptomics reveals key gene expression differences between the human and bovine pathogens of the Mycobacterium tuberculosis complex

• Published in: Microbiology (Society for General Microbiology) 2007-10, Vol.153 (10), p.3323-3336
• Main Authors: Golby, Paul, Hatch, Kim A, Bacon, Joanna, Cooney, Rory, Riley, Paul, Allnutt, Jon, Hinds, Jason, Nunez, Javier, Marsh, Philip D, Hewinson, R. Glyn, Gordon, Stephen V
• Format: Article
• Language: English
• Subjects: Acids - pharmacology; Anti-Bacterial Agents - pharmacology; Bacteriology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Humans; Microbiology; Mycobacterium bovis; Mycobacterium bovis - genetics; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Oligonucleotide Array Sequence Analysis; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.2007/009894-0

1 Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK 2 Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK 3 Bacterial Microarray Group, Department of Cellular and Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK Correspondence Stephen Gordon s.v.gordon{at}vla.defra.gsi.gov.uk 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. Abbreviations: DAT, diacyltrehalose; PAT, polyacyltrehalose; PDIM, phthiocerol dimycoserosate; PGL, phenolic glycolipid; PIN, PilT amino terminus; qRT-PCR, quantitative real-time PCR; TA, toxin–antitoxin Present address: Veterinary Exotic Diseases, Research and Official Controls Division (VEROD) Defra Area 101, 1a Page Street, London SW1P 4PQ, UK. Supplementary tables of primer sequences used for qRT-PCR reactions, and M. bovis and M. tuberculosis genes regulated in response to acid-shock are available with the online version of this paper.