NUS Pharmacy researchers have developed synthetic antimicrobial peptides which are capable of killing tuberculosis (TB) mycobacteria that cannot be eradicated by standard antibiotics. The research was led by Associate Professor Rachel Ee from NUS Pharmacy and published in Journal of Antimicrobial Chemotherapy.
The World Health Organization estimates that one third of the world’s population is infected with TB. Caused by the bacterium Mycobacterium tuberculosis, TB is a virulent disease that spreads from person to person through the air. In 2015, there were 2,000 new TB cases in Singapore among residents and long-staying foreigners.
Treatment for tuberculosis involves taking several drugs for six to nine months. Incomplete consumption of these drugs gives rise to resistance to the first-line drugs, after which second-line drugs need to be taken for up to two years. Explaining further, Assoc Prof Ee said, “Even more worrying now is that there are tuberculosis strains that are resistant to even second-line drugs, which means that no treatment options are available.”
The NUS research team have designed peptides that are effective against mutant TB strains. The peptides are tiny corkscrew-shaped molecules consisting of short chains of unnatural amino acids. When the peptides are inserted into mycobacterial cell walls, they create holes in them and damage the cell surface. This mechanism does not easily allow the mycobacteria to develop resistance against peptides. When combined with existing anti-TB drugs, the peptides can further enhance the effectiveness of the drugs.
The synthetic peptides were tested on drug-resistant mycobacteria in samples from TB patients, without any sign of resistance from the mycobacteria. The team also found that red blood cells were not harmed when the peptides were tested on them, showing that the synthetic peptides are non-toxic to the body.
The researchers will be working on extending the stability of the peptides through various chemical strategies and delivery methods.