Is there such a thing as a “mitotic accelerator” specific for tuberculosis?
Part of the seven-point action plan to fight Mycobacteria
tuberculosis (TB) is increased support for research and development of
anti-tuberculous drugs. (1) Most bacterial infections are cured after days
of antibiotic monotherapy, whereas several months of polytherapy are
required for TB. Prolonged treatment is probably required because of the
waxy outer coat and slow mitotic rate of this intramacrophage parasite.
Compliance with lengthy multi-drug therapy is hard to achieve for many
reasons, but compliance failure increases the risk of drug-resistant
Whilst isoniazid is bacteriostatic for resting bacilli, it is
bactericidal for rapidly dividing ones. It inhibits the synthesis of the
long chain mycolic acids required for the waxy coats. Rifampicin inhibits
RNA transcription and ethambutol, which is taken up most avidly by
mycobacterial cultures in the exponential growth phase, blocks the ability
of tubercle bacilli to build and maintain their waxy outer coats.
Resistance develops rapidly to any of these drugs when used alone. (2) As
isoniazid and ethambutol are particularly effective against rapidly
dividing bacilli, and as RNA synthesis and waxy coat construction must be
particularly crucial when new bacilli are being synthesised, it would seem
likely that TB bacilli are most weakened by antibiotics and most
vulnerable to successful macrophage attack whilst undergoing mitosis.
Therefore, if one could guarantee absolute antibiotic compliance over a
period of time, which is at least conceivable if appropriate depot
injections were developed, then the introduction of a “mitotic
accelerator” specific for TB to suitably antibiotic-primed patients could
transform the treatment of TB by placing the bacilli in their most
vulnerable state more frequently. Much shorter treatment courses with full
compliance might ensue, which would greatly reduce the risk of drug-
resistant tuberculosis into the bargain.
Has such a thing as a “mitotic accelerator” specific for TB already
been discovered or developed? If not, is it an idea worth exploring?
Combined with the right antibiotics, it could potentially become one of
the most important global developments in this emergent medical era of
deliberate manipulation of gene regulation and expression. Equivalent
products specific for particular lines of cancer cells could also hold
promise. Many cells are more vulnerable to successful attack during
mitosis so, having set a suitable trap, why not herd them into it?
1. Moszynski P. Experts devise strategy to fight new TB strain. BMJ
2. Dollery C, ed. Therapeutic Drugs, Second Edition. Edinburgh,
Churchill Livingstone 1999.
Competing interests: No competing interests