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Morphological Plasticity in Mycobacteria

29/4/2026

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Ms. Carolyn Mulu Wu, PhD student in A/Prof. Thomas Dick's lab, lead of the mycobacterial plasticity project
Generally mycobacteria are viewed as non-differentiating aerobic bacilli: they do not form specialized resting cells, need oxygen and are rod shaped. Mycobacteria can survive shock starvation in phosphate buffered saline (‘Loebel model’) in a nonreplicating state without any apparent morphological differentiation.
SPRINT-TB Theme 1 researchers had another look at this adaptation. Rather than shock starving the bacilli in saline, they added traces of a carbon source to the saline and observed the response of the bacteria. Interestingly, providing traces of a carbon source to
M. smegmatis in saline (as opposed to shock-starving the microorganism), resulted in the formation of a small-cell morphotype: reductive cell division generated very short rodshaped cells with increased long-term viability. Upon addition of rich medium, these small resting cells grew back to larger standard cells before commencement of the regular cell division cycle. The fact that a new morphotype can be so easily generated by slight changes in culture conditions supports the notion of a surprising morphological plasticity of mycobacteria.

These observations were described in Future Microbiology in April 2015 (Wu ML, Dick T. Metabolic flexibility and morphological plasticity in mycobacteria. Future Microbiol. 2015 Apr;10:449-52).

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Mechanism of Action of Perchlozone Solved

23/4/2026

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Ms. Pooja Gopal, PhD student in A/Prof. Thomas Dick's lab, lead of the perchlozone project
Perchlozone®, a new thiosemicarbazone class drug, was approved for treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia in 2012. The mechanism of action of the drug was at the time unknown. 
Another thiosemicarbazone is a well-studied old TB drug thiacetazone. It is known to inhibit the FASII dehydratase complex HadABC, which is involved in cell wall biosynthesis in Mycobacterium tuberculosis. Thiosemicarbazone is a prodrug requiring activation by the monooxygenase EthA.

SPRINT-TB Theme 1 performed a comparative in vitro analysis of both drugs. The two compounds were found to have an identical spectrum of activity. Spontaneous drug-resistant mutants exibited cross-resistance, which was mapped to HadABC and EthA, thereby suggesting that perchlozone, like thiacetazone, is activated by EthA with its principal target being HadABC.

The study was published in the International Journal of Antimicrobial Agents in April 2015 (Gopal P, Dick T. The new tuberculosis drug Perchlozone shows cross-resistance with Thiacetazone. Int J Antimicrob Agents. 2015 Apr;45(4):430-3.)

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