New weapon in fight against TB
doi:10.1038/nindia.2019.8 Published online 22 January 2019
Indian researchers have shown a better way to cure infections caused by pathogens such as Mycobacterium tuberculosis (Mtb), which make biofilms that create a physical barrier against drugs or immune surveillance.
Biofilms are formed by several proteins, including cyclophilins, and targeting and inhibiting their formation could be a strategy for intervention against bacterial pathogens, the researchers report1.
In their laboratory study using Mtb as a model, the researchers identified 'peptidyl-prolyl isomerase' (PpiB) as the cyclophilin directly involved in biofilm formation.
They then showed that the PpiB protein can be inhibited – and thereby biofilm formation suppressed – in the presence of the USFDA-approved drugs cyclosporine-A (an immuno-suppressant) and acarbose, a drug widely used in the management of type 2 diabetes.
"Cyclosporine-A, as an adjunct to existing anti-tubercular drugs, could be a potential strategy to address the problem of eradicating latent TB by first activating the bacterium by virtue of its immune-suppressive action, followed by the biofilm inhibition reported in our study," their report says. Using acarbose as an adjunct was also found to result in a reduction of the dosage of the anti-TB drug isoniazid.
Both cyclosporine-A and acarbose suppressed the formation of biofilms in Mtb, thereby exposing the bacterium directly to the drugs. "It points to their ability to act as therapeutic interventions to counter drug tolerance and also possibly reduce dosage of existing anti-tubercular drugs," the report adds.
Seyed Hasnain, head of Jamia Hamdard-Institute of Molecular Medicine in New Delhi and co-lead author, says the finding that the repurposed drugs are able to disrupt biofilm formation is not confined to just Mtb.
"That the drug binding site is shared by many other biofilm forming pathogens renders the use of these two repurposed drugs as a generic strategy for intervention against an array of such pathogens," he told Nature India.
1. Kumar, A. et al. Peptidyl-prolyl isomerase-B is involved in Mycobacterium tuberculosis biofilm formation and a generic target for drug repurposing-based intervention. NPJ Biofilms. Microbiomes. 5, 3 (2019) doi: 10.1038/s41522-018-0075-0