measurement-specific-mycobacterial-mistranslation-rates-with-gain

Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems

The translation of genes into proteins is prone to errors. Although the average rate of translational error in model systems is estimated to be 1/10,000 ...

Tsinghua University School of Medicine

Are antibodies important for protection against tuberculosis? The jury has been out for more than 100 years. B cell depletion in experimental Mycobacterium tuberculosis infection failed to identify a major role for these cells in immunity to tuberculosis. However, recent identification of naturally occurring antibodies in humans that are protective during M. tuberculosis infection has reignited the debate. Here, we discuss the evidence for a protective role for antibodies in tuberculosis and consider the feasibility of designing novel tuberculosis vaccines targeting humoral immunity.

Antibodies and tuberculosis: finally coming of age?

More than merely drug resistance.

Metrics commonly used to describe antibiotic efficacy rely on measurements performed on bacterial populations. However, certain cells in a bacterial population can continue to grow and divide, even at antibiotic concentrations that kill the majority of cells, in a phenomenon known as antibiotic tolerance. Here, we describe a form of semi-heritable tolerance to the key anti-mycobacterial agent rifampicin, which is known to inhibit transcription by targeting the β subunit of the RNA polymerase (RpoB). We show that rifampicin exposure results in rpoB upregulation in a sub-population of cells, followed by growth. More specifically, rifampicin preferentially inhibits one of the two rpoB promoters (promoter I), allowing increased rpoB expression from a second promoter (promoter II), and thus triggering growth. Disruption of promoter architecture leads to differences in rifampicin susceptibility of the population, confirming the contribution of rifampicin-induced rpoB expression to tolerance.

Babak Javid

Centre for Global Health and Infectious Diseases,
Collaborative Innovation Centre for the Diagnosis and Treatment of Infectious Diseases,
Centre for Global Health and Infectious Diseases, Collaborative Innovation Centre for the Diagnosis and Treatment of Infectious Diseases

Tsinghua University School of Medicine

Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems