New Delhi,15 January 2020- 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 antibacterials.
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
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
IIT Roorkee (https://www.iitr.ac.in/)
Roorkee is an institute of national importance imparting higher education in
engineering, sciences, management, architecture and planning, and humanities
and social sciences. Since its establishment in 1847, the Institute has played
a vital role in providing technical manpower and know-how to the country. In
the Times Higher Education Asia University Rankings 2019, the institute has
been ranked 3rd among the IITs, while on the citations criterion it has been
ranked 1st among all the Institutes in India.
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