IISc team moots alternative to antibiotic resistant infections

Bangalore Mirror Bureau | Jul 26, 2016, 04.00 AM IST

By: Mihika Basu

Nanoscale blockers plug pores formed by bacteria by 91%, stop cell death

Stating that antibiotic resistant bacterial strains have given rise to the so called 'superbug', which cannot be treated by known antibiotics, resulting in infections that are often fatal, professors at the Indian Institute of Science (IISc), Bangalore, have found a novel way of combating such bacteria.

Prof Prabal K Maiti from the Department of Physics and Centre for Condensed MatterTheory and Prof Ganapathy Ayappa from the Department of Chemical Engineering and Centre for Biosystems Science and Engineering, along with their research scholars Taraknath Mandal and Subbarao Kanchi, have come up with an alternative therapeutic strategy, where instead of targeting the bacteria with antibiotics, the nanosized pores formed by the bacteria in the host cellular membrane are blocked by what they call "synthetic polymers".

This, the researchers say, will prevent cell death and reduce the intensity of the infection. Results from computer simulations have shown that nanoscale blockers designed by the team can plug E.coli bacterial pores by a massive 91 per cent.

The findings have been published in the journal "RSC Nanoscale".

"Certain pathogenic bacteria have adopted a unique 'style' of killing it's victims by boring nanoscale holes into the host cellular membrane. Scientists across the globe have been actively working on designing various nanoscale (1-100 nanometre) blockers to plug these pores and prevent cell damage. Using computer simulations, we have suggested an effective nanoscale blocker made up of Polyamido-amine (PAMAM) dendrimers, a synthetic polymer. Each bacterial toxin will form a unique pore of a given size and structure with its own physical and chemical characteristics. We have investigated one such particular nanoscale pore formation by E.Coli and designed a blocker for this particular pore, which shows 91 per cent blockage," said Prof Ayappa.

This first-of-its-kind study has focused on the efficacy of the dendrimers in blocking pores formed by a pore forming toxin produced by certain strains of E.coli and other bacteria.

"Although this pore blocking strategy has the potential to treat a wide variety of pore mediated bacterial infections such as food poisoning, pneumonia, anthrax and cholera to name a few, theeventual success would depend on extensive laboratory and clinical testing," added Prof Maiti.

They have successfully demonstrated the potential of these dendrimers in plugging the pores formed by toxins released by the bacteria during an infection. It is these toxins that rapidly puncture the target cell membrane, and the cell leaks to death in a process known as apoptosis.

Funded by the Department of Science and Technology (DST), this work is part of a larger collaborative interdisciplinary research initiative at IISc, aimed at understanding the interactions of proteins and nanoparticles on biological membranes.

Prof Ayappa elaborated that these predictions were based on accurate computer simulations carried out at the high performance computing facility at IISc. "Once these predictions are verified in the laboratory, drug formulations can be tested using a variety of dendrimer blockers on pores implicated in other diseases as well. That will be the next step in our research work. Extensive studies will have to be conducted at the clinical level to exploit this novel concept. It could be administered orally or delivered locally," he said. The word 'dendrimer' refers to a molecule with tree-like branching and is highly regarded in modern nanotechnology due to its flexible properties. Polyamido-amine is a type of star-shaped dendrimer with repetitive branched subunits of amide and amine functional groups. "The structure and size or generation of the dendrimer depends on the extent of branching in the molecule," said Prof Maiti.

While designing a specific dendrimer to effectively block the pore, both the size of the dendrimer molecule and its charge, are important factors, explained the authors.