The Genetic Requirements for Fast and Slow Growth in Mycobacteria

• DOI: 10.1371/journal.pone.0005349
• Publication Date: 2009-04-27T23:10:05Z
• Authors: Dany J. V. Beste; Mateus Espasa; Bhushan Bonde; Andrzej M. Kierzek; Graham R. Stewart; Johnjoe McFadden
• Keywords: Chemostat

Mycobacterium tuberculosis infects a third of the world's population. Primary involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which characterised slow or non-replicating bacteria. Reactivation infection switch back to can lead post-primary transmissible tuberculosis. Mycobacterial mechanisms involved in growth switching rate provide rational targets for development new drugs against persistent mycobacterial infection. Using chemostat culture control rate, we screened transposon mutant library Transposon site hybridization (TraSH) selection define genetic requirements and bovis (BCG) rate. We identified 84 genes that are exclusively required (69 hours doubling time) 256 from growth. To validate these findings performed experiments using individual M. BCG knock out mutants. have demonstrated carefully orchestrated process requires distinct set encoding several virulence determinants, gene regulators, metabolic enzymes. The mce1 locus appears be component consistent with proposed role These results suggest novel perspectives unravelling between acute TB infections means study aspects this important phenomenon vitro.