title: Differential expression of a virulence factor in pathogenic and non-pathogenic mycobacteria.
abstract: The pathogenicity of mycobacterial infections depends on virulence factors that mediate survival inside host macrophages. These virulence factors are generally believed to be specific for pathogenic species and absent or mutated in non-pathogenic strains. The serine/threonine protein kinase G (PknG) mediates survival of mycobacteria within macrophages by blocking lysosomal delivery. Here we describe a gene of the non-pathogenic species Mycobacterium smegmatis that is 78% identical with pknG of Mycobacterium tuberculosis and M. bovis bacillus Calmette-Guérin (BCG). When cloned into expression vectors, the M. smegmatis pknG orthologue produced an active kinase and performed the same function as its M. bovis BCG counterpart in intracellular survival. In addition, similar levels of pknG transcripts were found in M. bovis BCG and M. smegmatis. However, virtually no translation product of chromosomal pknG could be detected in M. smegmatis both after in vitro growth and after macrophage infection. This lack of efficient translation was shown to be caused by regulatory elements in the upstream region of the M. smegmatis gene. The data reveal dramatically increased translational efficiency of a virulence gene in a pathogenic mycobacterium compared with a non-pathogenic mycobacterium suggesting that changes in expression levels may underlie evolution of pknG and other pathogenicity genes in mycobacterium.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Edith N G
authors.initials: EN
authors.lastname: Houben
authors.forename: Anne
authors.initials: A
authors.lastname: Walburger
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ferrari
authors.forename: Liem
authors.initials: L
authors.lastname: Nguyen
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Thompson
authors.forename: Christian
authors.initials: C
authors.lastname: Miess
authors.forename: Guido
authors.initials: G
authors.lastname: Vogel
authors.forename: Bernd
authors.initials: B
authors.lastname: Mueller
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D014176:Protein Biosynthesis; D012329:RNA, Bacterial / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D037521:Virulence Factors; D017869:Cyclic GMP-Dependent Protein Kinases