Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections.

"We have assembled the largest M. tuberculosis transcriptional-regulatory network to date, and characterized the temporal response of this network during adaptation to stationary phase and hypoxia, using published microarray data. Distinct sets of transcriptional subnetworks (origons) were responsive at various stages of adaptation, showing a gradual progression of network response under both conditions."

Tremendous resources are being directed towards fundamental and applied research on Mycobacterium tuberculosis. Concurrently, diseases caused by other, non-tuberculous mycobacteria (NTM), are on the rise in many settings. For many of these ‘atypical mycobacteria’, there is no genome sequence data and a limited understanding of their biology. Consequently, they are often felt to be ‘ubiquitous’ in the environment and that disease occurs largely independent of bacterial factors, in an immunocompromised host. As the distribution of these organisms in human and environmental samples is decidedly non-random, there is indirect evidence that exposure, infection and disease due to these organisms are in part determined by bacterial factors. Knowledge on how different mycobacterial species engage the host differently will help provide predictive information on the epidemiology and biology of infection with these organisms. Already, post-genomic study of M. avium has pointed to the existence of variable genomic regions that likely represent mycobacterial pathogenicity islands. An additional benefit of further genomic study of NTM will be the provision of an out-group to better appreciate M. tuberculosis, potentially explaining the sequence of genomic events that originally permitted an environmental mycobacterium to evolve into a host-associated pathogen.