Breakthrough: Fighting 'superbugs' using skin as shield

In what appears to be a significant breakthrough that has the potential to aid millions of people, a team of scientists — from industry and academia — have discovered a way to stimulate skin cells to secrete naturally occurring antibiotics called Antimicrobial Peptides (AMPs).

That AMPs target and kill bacteria in such variable ways that very few bacteria ever become resistant to these, makes them uniquely suited to treat antibiotic-resistant bacteria, also called “superbugs”.

Superbugs have evolved so many clever ways of protecting themselves against antibiotics that the World Health Organisation (WHO) now fears that humanity may slip back to the pre-antibiotic era.

The death toll caused by antimicrobial resistance is estimated to rise to 10 million per annum by 2050 with India carrying one of the largest burdens of drug-resistant pathogens worldwide.

In the context of such public health threat, scientists from the Institute for Stem Cell Science and Regenerative Medicine (inStem) and Unilever joined together to work on innovative strategies to deal with antimicrobial resistance and probed the cellular mechanisms that regulate the release of AMPs.

“AMPs are a diverse class of naturally occurring molecules that utilize varied modes of bactericidal activity, which may be harnessed as a strategy to avoid the development of bacterial resistance to these compounds,” the research paper reads.

While there has been a lot of work going on globally about finding ways to harness AMPs, as of now, no one has been able to artificially create effective AMPs for use as an antibiotic and the new findings by inStem and Unilever scientists has found a way to overcome this limitation.

The findings have been published with the national center for biotechnology information (NCBI) — part of the United States National Library of Medicine, a branch of the National Institutes of Health — is in this context.

“The skin is the body’s first line of defence against the external environment. This is mainly accomplished via three modes: First, the layer of elaborate cross-linked proteins in a lipid matrix that form a physical barrier; second, commensal bacteria on the surface of the skin that counteract pathogenic bacteria and third a rich reservoir of AMPs with bactericidal activity that form a biochemical barrier,” the research paper reads.

And, apart from their role as natural antibiotics, AMPs are also known to be involved in wound healing in the skin. This spurred Amitabha Majumdar (Unilever R&D) to hypothesize that the same machinery used to release AMPs during wound healing could be harnessed to control AMP release from skin cells for treating or preventing infections.

To test this, Majumdar contacted Colin Jamora from inStem’s centre for inflammation and tissue homeostasis, whose group works extensively on the mechanisms of wound healing in skin. The team — Majumdar and Jamora along with Bhatt T, Bhosale A, Bajantri B, Mathapathi MS, Rizvi A, and Scita G, — together discovered a new signalling pathway for long-term release of AMPs.

“Usually, AMPs are released to fight off bacterial infections when direct contact between skin epidermal cells and bacteria occur, and this process is triggered by a reduction in the levels of a protein called caspase-8,” the scientists said.

Researchers then found that reducing caspase-8 via molecular techniques is also enough to trigger the release of stored AMP from skin cells. Just by modulating caspase-8 levels in the skin, AMP release can be controlled to prevent a whole spectrum of infections; this may be especially useful for diabetics and patients with weakened immune systems who are highly susceptible to bacterial, yeast, fungal, and viral infections in post-surgery wounds.

Terming it a fruitful collaboration, Jamora and Majumdar emphasised on how partnerships between academic institutions and industry can benefit consumers and society.