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Lipid bodies help antibiotics to kill TB infections

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Posted July 3, 2019

Researchers are a step closer to better understanding how to treat one of the world’s deadliest diseases tuberculosis (TB), according to a new study published in Science.

TB was one of the top 10 causes of death worldwide with 1.6 million deaths in 2017 according to the World Health Organization.

In the study co-led by Dr Haibo Jiang from UWA, the team identified how lipid bodies – fat-rich structures inside human cells – could help bedaquiline, a TB drug, to kill TB infections.

In some people, infection with the microbe Mycobacterium tuberculosis can lead to serious illness, and even death. In others it is harmless. Image credit: NIAID via Flickr, CC BY 2.0

In some people, infection with the microbe Mycobacterium tuberculosis can lead to serious illness, and even death. In others it is harmless. Image credit: NIAID via Flickr, CC BY 2.0

TB is caused by the pathogenic bacteria mycobacterium tuberculosis (Mtb), intracellular pathogens that infect and grow inside host cells.

“A crucial question in the treatment of diseases caused by intracellular pathogens such as Mtb is whether drugs effectively target bacteria within host cells,” Dr Jiang said.

Co-author Daniel Greenwood, from The Francis Crick Institute said bedaquiline was the first newly approved antibiotic for TB treatment in 50 years.

“But until now, we didn’t understand how a compound that that is insoluble in water could be so effective in treating TB,” Mr Greenwood said.

The UWA team, with researchers from The Francis Crick Institute and GlaxoSmithKline, developed a new drug-imaging method that involves the use correlative light, electron and ion microscopy.

“Our new drug imaging method makes it possible for us to fill gaps in our understandings of drug mechanisms,” Dr Jiang said. “This study showed that bedaquiline accumulates in lipid bodies and it helps the delivery of the drug to Mtb within host cells.”

Compounds that only dissolve in lipids, known as lipophilic compounds, are often abandoned during drug development because they tend to bind to proteins and fats in our bodies in a non-specific way.

“Our surprising findings show that even very lipophilic antibiotics like bedaquiline are worth pursuing in drug development,” Mr Greenwood said.

“Unfortunately multidrug-resistant TB has been a public health crisis with only 55 per cent of multidrug-resistant TB patients successfully treated,” Dr Jiang said.

The researchers plan to further study the working mechanisms of antibiotics and hope to provide new ideas to improve treatments and design new antibiotics to treat TB in the future.

Source: The University of Western Australia

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