Researchers to use live human Tb bacteria in new lab

University of Otago postdoctoral fellow Dr Ildiko Pecsi (right), who was born in Hungary, and...
University of Otago postdoctoral fellow Dr Ildiko Pecsi (right), who was born in Hungary, and German-born assistant research fellow Marion Weimar will soon be undertaking tuberculosis research in this new state-of-the-art containment laboratory. Photo by John Gibb.
University of Otago microbiologist Prof Greg Cook and the university's new infectious disease containment laboratory have found themselves in the research front line in the international war against tuberculosis.

Clad in spacesuit-like protective gowns, researchers will from next month begin using the PC3 laboratory to take to the next level their work in trying to counter human tuberculosis.

They will use live human Tb bacteria for the first time, under strictly controlled conditions.

The laboratory offers the second highest possible level of biohazard protection.

It is the first PC3 facility in Dunedin, and only the second in the South Island.

Global tuberculosis figures made ''incredibly frightening'' reading, Prof Cook said.

About 1.7 million people die each year from the disease.

There are 10 million new cases each year and two billion of the planet's about seven billion overall population have been infected and carry a latent form of the disease.

And Prof Cook warned of the growing problem of drug resistance. Some strains of tuberculosis were now resistant to each of the 10 traditional mainstream drugs against Tb.

Only one new anti-Tb drug has been officially licensed in the past 40 years - bedaquiline, which was licensed by the US Food and Drug Administration (FDA) late last year.

Although 99% of the disease burden is carried in developing countries, modern air links mean new arrivals with drug-resistant strains of Tb from places such as India and Indonesia, where the disease is endemic, are already arriving at Auckland Airport.

Otago had its first case of an extensively resistant strain of Tb in 2010. Against this stark background, Prof Cook, who holds a prestigious James Cook Fellowship from the Royal Society of New Zealand,

is collaborating with Belgium-based drug researchers in trying to clarify exactly how bedaquiline works, at the molecular level.

If Otago researchers could help clarify the drug's molecular mechanism, it could lead to the development of further much-needed drugs to counter Tb drug-resistance, he said. In 2005, Prof Cook and research colleagues discovered that an enzyme, called F1FO ATP synthase, was essential for the growth of the deadly pathogen Mycobacterium tuberculosis.

''We believe that's its Achilles heel.''

Unknown to the Otago researchers, other researchers at Tibotec/Johnson and Johnson in Belgium had just discovered a new drug - bedaquiline - which was active against Mycobacterium tuberculosis and ''targeted the very enzyme we were working on''.

Most existing drugs target the bacterial cell wall, rather than an enzyme critical to the organism's energy source. The enzyme is found in mitochondria, the power-pack within Tb cells.

This enzyme is essentially the same as that found in human mitochondria; just one crucial amino acid is different. And that one amino acid made a huge difference, effectively protecting the human host and exposing the bacterial pathogen to a new form of attack.

''That's the window, that's the magic bullet that we never, ever would have thought would work.''

Otago researchers were working to unravel the mystery of exactly how - at the molecular level - the new drug was killing the bacteria, he said.

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