After two years of research, scientists at the National University of Singapore have developed synthetic antimicrobial peptides that create drug passageways for antibiotics to fight TB bacteria.

The peptides are corkscrew-shaped molecules which drill into the bacteria's cell membranes, creating passageways for drugs to infiltrate and kill the bacteria. In laboratory tests, the bacteria were found to develop slower drug resistance when this combination of peptides and drugs were used.

Patient samples laced with drug resistant bacteria were also tested on and it was found that the bacteria did not develop any signs of resistance against these peptides.

"Tests on human blood also found that the red blood cells were not damaged, even when the dosage was increased twentyfold or thirtyfold," said Associate Professor Rachel Ee, who led the research.

The team also said that the peptides enhanced the effectiveness of the drugs, which could minimise the dosage of medication and shorten the length of treatment. This is useful, especially when compliance with the treatment regime is an issue with patients who consume a cocktail of drugs for six to nine months - or up to two years for patients with drug resistant TB.

More than a decade before new treatments are available

A major challenge with peptide drugs is their short lifespan as they can be degraded by enzymes in the bloodstream; therefore the team added artificial amino acids to allow drugs to stay intact in the body longer.

The use of peptides as the development of new treatments can take up to 10-15 years, and whether the addition of artificial sequences will work in the human body, or cause adverse side effects is still unknown, but Professor Ee said that this the research offers a step forward in the fight against multi-drug resistant TB.

"It will open up new approaches and avenues for tackling the drug resistance problem," she added.

The study was done in collaboration with the Agency for Science, Technology and Research's Institute of Bioengineering and Nanotechnology and Imperial College London. The researchers have also secured a second round of funding from the National Medical Research Council last month to continue the research.

In 2015, there were 2,000 new TB cases among Singapore residents and long-staying foreigners and in June 2016, there was an outbreak in Ang Mo Kio where six individuals were diagnosed over four years with the same multi-drug resistant strain. The cause is still unidentified.

Globally, 10.4 million people were infected with TB in 2015 and around 3% contracted a multi-drug resistant strain. The infectious disease that killed 1.8 million people worldwide in 2015 is gaining momentum and has presented itself as a pressing issue especially in recent concerns about the rise of superbugs.

Deciphering the genetic code responsible for dormancy

Back in November 2016, a separate team of researchers from Singapore-MIT Alliance for Research and Technology (Smart) have discovered a new fundamental mechanism that is responsible for when and how TB bacteria go into dormancy. The research is significant as antibiotics are ineffective when the bacteria is dormant, allowing recurrent lapses in the future.

"The ultimate goal is to cut down the time we need to treat TB," said Dr. Chionh Yok Hian, Smart postdoctoral associate and lead author of the research. "More broadly, this allows the ability to target drug resistance, which is a growing concern worldwide."

The team examined changes in protein levels when the bacteria were starved of oxygen and discovered a mechanism that bacteria use to adapt to environmental changes.

The discovery of an alternative genetic code - that is very likely to be present in all bacteria - identifies the sequence of which genes are prioritised to be expressed. The code enables the bacterium to alter how much and which proteins it produces to allow it to enter dormancy and reactivate once the host's immunity if compromised.

"This enables the precise scheduling of gene products required to respond to starvation or to develop drug resistance," said Professor Peter Dedon, Smart principal investigator of the Infectious Diseases Interdisciplinary Research Group.

The group is working with the Experimental Therapeutics Centre of A*STAR to develop new classes of antibiotics. MIMS

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