MUTATION OF THE PRINCIPAL SIGMA-FACTOR CAUSES LOSS OF VIRULENCE IN A STRAIN OF THE MYCOBACTERIUM-TUBERCULOSIS COMPLEX

Tuberculosis continues to be responsible for the deaths of millions of people, yet the virulence factors of the causative pathogens remain u nknown. Genetic complementation experiments with strains of the Mycoba cterium tuberculosis complex have identified a gene from a virulent st rain that restores virulence to an attenuated strain. The gene, design ated rpoV, has a high degree of homology with principal transcription or sigma factors from other bacteria, particularly Mycobacterium smegm atis and Streptomyces griseus. The homologous rpoV gene of the attenua ted strain has a point mutation causing an arginine --> histidine chan ge in a domain known to interact with promoters. To our knowledge, ass ociation of loss of bacterial virulence with a mutation in the princip al sigma factor has not been previously reported. The results indicate either that tuberculosis organisms have an alternative principal sigm a factor that promotes virulence genes or, more probably, that this pa rticular mutant principal sigma factor is unable to promote expression of one or more genes required for virulence. Study of genes and prote ins differentially regulated by the mutant transcription factor should facilitate identification of further virulence factors,