Researchers at the Indian Institute of Technology, Roorkee have discovered a novel compound that can effectively kill a multitude of notorious antibiotic resistant bacteria.
Antibiotics have been considered as the cornerstones of both basic and modern medicine and it is difficult to envisage a world without them. However, injudicious over the counter sales and excessive use and abuse of antibiotics in poultry, livestock and agriculture has given rise to the global problem of antibiotic resistance.
With the ever-increasing rise in drug resistant superbugs and lack of effective antibiotics against them, it has become imperative to search for novel antibacterial molecules. Moreover, gram negative bacterial pathogens present a major threat owing to their outer membrane permeability barrier and presence of efflux pumps that may act as tiny motors to flush antibiotics out of the bacterial cells.
In a new study published in the journal, ‘Journal of Antimicrobial Chemotherapy’, IIT Roorkee researchers screened a library of 11,000 compounds against the Gram negative bacteria, Escherichia coli and discovered 30 novel potent anti-bacterials.
The research team led by Dr. Ranjana Pathania, Associate Professor at the Department of Biotechnology, IIT Roorkee identified a small molecule “IITR06144” that can kill highly multidrug resistant strains of Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia as well as Mycobacterium tuberculosis. The molecule also showed promising activity against the diarrhoea causing bacteria, Clostridium difficile and the wound pathogen, Staphylococcus aureus.
The aim of this study was to evaluate the biological properties of a small molecule, IITR06144, identified in a phenotypic screen against the Gram negative model organism Escherichia coli.
The team compared the properties of IITR06144 with structurally analogous antibiotics Nitrofurantoin and Furazolidone, which are commonly administered in clinics for the treatment of urinary tract infections (UTIs) and intestinal ailments respectively. UTIs are one of the world’s most common infections known to be associated with frequent cases of recurrence in female patients. Considering the global antibiotic resistance catastrophe, only a few “front-line” drugs prove to be effective against them. IITR06144 inhibited the growth of several nitrofurantoin resistant UTI pathogens isolated from clinics and proved to be a powerful weapon against antibiotic tolerant E. coli strains, which are responsible for infection relapse and recurrence.
IITR06144 acts by targeting multiple pathways in the bacterial cell such as DNA repair and cell division machinery. Since multi-targeting antibiotics are less prone to resistance generation, therefore IITR06144 holds immense therapeutic potential as a novel antibacterial. Importantly, while most of the antibiotics currently prescribed in clinics seem to kill the healthy gut bacteria, IITR06144 did not inhibit them, this being one of the most desirable properties of a novel antibacterial.
IITR06144 also displayed considerable in vivo efficacy to rescue mice suffering from A. baumannii infection, which is one of the most troublesome pathogens and tops the WHO’s (World Health Organisation) list of threats that urgently need new antibiotics.
Timsy Bhando, Tapas Bhattacharyya, Amit Gaurav, Jawed Akhter, Mahak Saini, Vivek Kumar Gupta, Santosh Kumar Srivastava, Himanshu Sen, Naveen K Navani, Varsha Gupta, Debasis Biswas, Rama Chaudhry, Ranjana Pathania, Antibacterial properties and in vivo efficacy of a novel nitrofuran, IITR06144, against MDR pathogens, Journal of Antimicrobial Chemotherapy, dkz428, https://doi.org/10.1093/jac/dkz428