Avipsha Datta, Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta
Antibiotics were considered to be “wonder drugs” in the 20th century. But, as days passed, we started the over usage of these medicines and basically helped the bacteria to become pretty clever and evade these wonder drugs, that is, they developed resistance! Antibiotic resistance occurs when bacteria change themselves in response to the use of these medicines-they produce enzymes that help them to develop the resistance. The emergence of multi-drug resistant organisms (MDROs) is a global public health issue, severely hindering the antimicrobial therapy. Hence, the advent of new drugs are an immediate necessity.
Drug repurposing is a drug development strategy during which new pharmaceutical applications are identified for already approved drugs.
From the viewpoint of the development of virulence inhibitors, inhibition of Quorum Sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS gene expression.
In a study conducted by Molecular biologist Bonnie Bassler and her graduate student Justin Silpe revealed that viruses can use quorum-sensing chemicals released by bacteria to determine when best to start multiplying and murdering.
Gajdács et al. conducted an experiment with 45 pharmacological agents with a wide spectrum of different chemical structures and mechanism of actions. The antimicrobial activity of these compounds was tested using the Broth Microdilution Method. Screening and semi-quantitative assessment of QS- inhibition by the compounds was performed using QS-signal molecule-producing and indicator strains.
14 out of 45 showed antibacterial activity in the tested concentration range, while 8 of them(5-fluorouracil, metamizole-sodium, cisplatin, methotrexate, bleomycin, promethazine, chlorpromazine and thioridazine) showed dose-dependent QS inhibitory activity in the in-vitro model systems used during the experiment.
These results opened a huge arena for the use of drugs other than antimicrobials to treat microbial infection, that is the beauty of drug repurposing! Virulence inhibitors represent an attractive alternate strategy to combat bacterial pathogens, thereby helping us to cope up with the problem of antimicrobial resistance. Some of the non-antibacterial drugs showed promising QS inhibitory results, the exact accuracy of which could be determined by further experiments. Thus, drug repurposing is a very promising area of this new age Biology, research studies in which will help us to overcome various problems which are an inherent part of the biological world.
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