Otago microbiologist leading fight against tuberculosis

University of Otago postdoctoral fellow Dr Ildiko Pecsi (right), who was born in Hungary, and German-born assistant research fellow Marion Weimar. Photo / 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 space-suit-like protective gowns, researchers will from next month begin using the PC3 laboratory to take their work in trying to counter human tuberculosis to the next level.

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 make "incredibly frightening" reading, Prof Cook says.

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 warns of the growing problem of drug resistance. Some strains of tuberculosis are now resistant to each of the ten traditional mainstream drugs against Tb.

And 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.

And although 99 per cent of the disease burden is carried in developing countries, modern air links mean that new arrivals with drug-resistant strains of Tb, from places like 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 has found himself working in one of the hottest new research fields in the war against tuberculosis.

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 the world's newest anti-Tb drug, bedaquiline, works, at the molecular level.

If Otago researchers can help clarify the new drug's molecular mechanism, it could lead to the development of further much-needed drugs to counter the growing wave of Tb drug-resistance, he says.

Back 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 that "targeted the very enzyme we were working on".

This is a novel target for anti-Tb drugs, with most existing drugs targeting 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, except for one crucial amino acid which was different.

And that one amino acid ultimately 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.