Researchers Find A Potent Molecule To Fight Multidrug-Resistant Bacteria

Researchers from the Indian Institute of Technology (IIT) Roorkee found a new molecule that has the potential to kill multidrug-resistant Bacteria.

For finding the new molecule, researchers from IIT Roorkee have screened a small-molecule library of 11,000 compounds.
They found a potent molecule that belongs to nitrofuran class of antibiotics – nitrofurantoin and furazolidone – to exhibit broad-spectrum bacterial activity against multidrug-resistant bacteria like E. Coli, Mycobacterium tuberculosis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus and Clostridium difficile.

The researchers have tested the molecule in mice infected with sepsis-causing bacteria A. baumannii.
The molecule reduced the bacterial load significantly in the spleen, kidney, lungs and liver.
Only half the dose of the new molecule compared to nitrofurantoin was enough to reduce the bacterial load.
The researchers found that the molecule kills the bacteria in two ways.
It damages the DNA of the bacteria by inhibiting cell division.
When half the dose to kill the bacteria was used, the molecule hindered cell division in daughter cells leading to the bacteria forming into long filaments.
Because of the two pathways in which the molecule kills the bacteria, developing resistance by the bacteria will take a very long time, explains the researchers.
They also found that, even at a low 16-fold concentration, the molecule was able to kill E. Coli compared to nitrofurantoin.
The molecule was also effective against both gram-negative and gram-positive bacteria and anaerobic bacteria.
Also, persister bacteria that are dormant were also killed by the molecule.

The researchers generated mutants of the molecule and developed a pro-drug.
This pro-drug will become active only after getting inside the body of a bacteria, thereby limiting the scope of bacteria to develop resistance.
Also, the components formed by the pro-drug are potent and short-lived, thus leaving less time for bacteria to develop resistance.

The molecule was effective at inhibiting bacteria’s ability to develop biofilm, the protective layer that bacteria use against antibiotics.
It is also effective at disrupting already formed biofilms.
The researchers also found that the bacteria’s mechanism to flush out drugs from its body through efflux pumps was ineffective against the new molecule.
Also, the tested the molecule to see whether reactive oxygen species (ROS) were generated to kill the bacteria.
They found that ROS was produced after the bacterial kill. That means formation of ROS is a consequence of the bacterial kill and not the killing mechanism.