Researchers have discovered that the ratio of precursor-rRNA (pre-rRNA) to total 23S rRNA (pre-rRNA/23S) can be used as an accurate, early biomarker for TB treatment response. Treatment failure and relapse are often caused by sub-populations of “persister” bacteria that survive early bactericidal killing. Persisters are targeted in the “sterilizing” phase of treatment. Existing culture-based markers of treatment efficacy fail to accurately predict failure and relapse, likely because they reflect the number of bacteria killed in the early bactericidal phase rather than drug activity in the subsequent sterilizing phase of treatment. The pre-rRNA/23S ratio indicates the rate of ongoing Mycobacterium tuberculosis (Mtb) rRNA synthesis, and can be used to successfully monitor “persisters” during the sterilizing phase. The inventors showed that in human sputum standard TB treatment suppressed the Mtb pre-rRNA/23S ratio. This method described can be used for monitoring drug efficacy or identifying relapse risk in TB patients and has the potential to be used to monitor other chronic bacterial infections.
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