Combining anti-TB drugs for new treatment approach
Postdoctoral research fellow, Charles Omollo,
is based in the South African Medical Research
Council / National Health Laboratory Service /
UCT Molecular Mycobacteriology Research Unit
at the IDM and Department of Pathology..
Tuberculosis (TB) is the top infectious disease killer in the world, with one in four people estimated to be infected by TB bacteria. As TB Awareness Month is commemorated globally in March, researchers at the University of Cape Town’s (UCT) Institute of Infectious Disease and Molecular Medicine (IDM) have published a paper in Antimicrobial Agents and Chemotherapy, a leading journal of the American Society for Microbiology.
The paper, Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistant Mycobacterium tuberculosis, describes the use of newly designed drug combinations against drug-resistant strains of Mycobacterium tuberculosis (M. tb), the bacterium which causes TB. The paper highlights two key results; the first is the powerful anti-mycobacterial activity of the two-drug combination of spectinomycin and chlorpromazine. Approved for use in tackling other conditions, the drugs have very limited effect against M. tb on their own but are shown here to be effective when used in combination. This result also provided compelling evidence that chlorpromazine inhibits a key mycobacterial efflux pump used by M. tb to force out other antibiotics, thereby limiting their effect.
The second result is the potential for strongly synergising drug combinations to be effective in cases where pre-existing genetic resistance is already present. That is, a strategy to preserve the usefulness of antibiotics against which M. tb is already resistant.
The paper, Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistant Mycobacterium tuberculosis, describes the use of newly designed drug combinations against drug-resistant strains of Mycobacterium tuberculosis (M. tb), the bacterium which causes TB. The paper highlights two key results; the first is the powerful anti-mycobacterial activity of the two-drug combination of spectinomycin and chlorpromazine. Approved for use in tackling other conditions, the drugs have very limited effect against M. tb on their own but are shown here to be effective when used in combination. This result also provided compelling evidence that chlorpromazine inhibits a key mycobacterial efflux pump used by M. tb to force out other antibiotics, thereby limiting their effect.
The second result is the potential for strongly synergising drug combinations to be effective in cases where pre-existing genetic resistance is already present. That is, a strategy to preserve the usefulness of antibiotics against which M. tb is already resistant.
“Identifying potent, new multi-drug combinations for M. tb is one of several approaches towards combating the emergence and spread of drug-resistant TB, especially the more problematic multi- and extensively drug-resistant forms,” said Postdoctoral research fellow, Charles Omollo, the lead author of the paper and a Carnegie Developing Emerging Academic Leader.
“We have prioritised a drug repurposing strategy which aims to identify potent compounds and combinations from existing clinically approved agents which might not necessarily possess anti-TB activity individually. In addition to identifying new combinations, we also aim to understand the mechanisms underlying the observed potentiation effects, thereby facilitating the future development of other drugs and regimen designs that can incorporate this knowledge,” he said.
Read the paper here.