In a remarkable development that holds the potential to revolutionise the diagnosis of Tuberculosis (TB) through culture diagnostics, a groundbreaking study has unveiled an unexpected behavior in peptides. This research, recently published in the scientific journal Microorganisms https://www.mdpi.com/2076-2607/11/9/2225, may prove to be a crucial puzzle piece in the battle against one of the world’s deadliest diseases.
For the very first time, scientists have identified a hormetic response induced by antimicrobial peptides (AMPs) in slow-growing mycobacteria, including Mycobacterium tuberculosis, the bacterium responsible for TB. A hormetic response is a biological phenomenon in which a low dose of a substance stimulates the organism, while a high dose inhibits it.
Antimicrobial peptides, which consist of short chains of amino acids, are commonly recognized for their ability to kill bacteria. However, the groundbreaking discovery lies in the fact that at lower concentrations, these peptides actually stimulate the growth of specific mycobacteria, rendering them more detectable. “This is a paradigm shift in how we perform culture diagnostics in TB. For decades, culture diagnostics has not seen changes in the media used,” commented Tim Bull, director of TiKa Diagnostics Ltd.
The implications of this discovery are staggering. As per the World Health Organisation, TB continues to rank among the top 10 causes of death globally. Antibiotic resistance in M. tuberculosis is on the rise, making it all the more urgent to find innovative diagnostic approaches. “Despite much faster diagnostics available, culturing M. tuberculosis is the gold standard because it is still the only method allowing testing for all antibiotic sensitivities. Imagine reducing the time it takes to provide such information, getting patients the treatment they need faster, and curbing the spread of the disease. That’s the kind of impact we’re talking about,” explained Kai Hilpert, director of TiKa Diagnostics Ltd.
Mycobacterium tuberculosis is known for its slow growth, dividing only every 16-20 hours, in stark contrast to bacteria like E. coli, which can divide every 20 minutes. The AMPs identified in this study have the potential to significantly shorten the time needed to confirm a TB diagnosis, particularly when bacterial levels are low. This presents a quicker and more sensitive approach to TB testing.
Additionally, this research underscores the versatility of peptide-based technology, with potential applications that extend beyond human diagnostics to include animal health. This breakthrough paves the way for a new era in the management of infectious diseases, not limited to TB but potentially applicable to other mycobacterial infections as well.
The study involved a comprehensive screening process that encompassed both designed and naturally occurring peptides. Notably, Lasioglossin LL-III from bees and Ranacyclin E from frogs emerged as the most potent natural peptides. The study also brought attention to Peptide 14, which exhibited growth-stimulating activity across a wide concentration range, along with its stability-optimised variant, Peptide 14D, which demonstrated a more specific activity range. These peptides are not mere scientific curiosities; they are already being commercially employed by TiKa Diagnostics Ltd to enhance the recovery and culture diagnostics of mycobacteria in both humans and animals.