Wits node is "waking up" TB?

MAY 2005

Researchers in the Wits University / NHLS node of the CBTBR have made a significant breakthrough in understanding how Mycobacterium tuberculosis (Mtb) ‘wakes up’ from a state of ‘dormancy.’ Their research focused on the role of resuscitation-promoting factor (Rpf) homologues in the resuscitation (reawakening) of Mtb from a state of ‘non-culturability’, i.e. in which it is unable to form colonies on agar plates. The study involved creating mutant strains of Mtb that lack three of the five Rpfs present in this organism, and then assessing the effect of loss of these factors on resuscitation. Writing in the May 2005 issue of Infection and Immunity, Katrina Downing and Valerie Mizrahi, together with colleagues from Aberystwyth (Wales) and Moscow (Russia), reported that the Rpf-deficient mutant strains were unable to resuscitate when placed in fresh media, whereas wild type bacteria resuscitated perfectly well. These mutants were also impaired in their ability to grow in a mouse model of tuberculosis, suggesting a tantalizing link between resuscitation of Mtb and its ability to cause disease. This collaborative project was initiated in the Mizrahi laboratory over six years ago and was funded by grants from the GlaxoSmithKline Action TB Initiative and THRIP and currently is being further developed by Bavesh Kana, Bhavna Gordhan and Edith Machowski in the CBTBR.

Previous infection increases TB risk?

MAY 2005

Writing in the American Journal for Critical Care and Reproductive Medicine, researchers at the SU node show through the analysis of clinical data and the DNA fingerprinting of the disease causing strains of Mycobacterium tuberculosis that patients who have had an episode of TB in the past are at a four-fold higher risk of developing a subsequent episode. This demonstrates that there is an extremely high infection pressure from infectious individuals who are not receiving anti-tuberculosis therapy. TB control needs to lower this infection pressure to limit spread of the disease to uninfected individuals as well as individuals who have had TB. The fact that an individual may have a second episode of TB is strong evidence supporting genetic and/or environmental factors as susceptibility factors. This finding has major implications for vaccine development and vaccine use as it demonstrates that a previous infection and/or disease with a virulent strain is unable to afford protection. Furthermore, this suggests that TB patients need to be close followed to identify subsequent disease episodes.