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Putting antibiotic-resistant bugs under the microscope

Professor Ben Adler is interested in the smallest things, which also happen to be among the deadliest: microscopic bacteria that can cause fatal infections in animals and humans. In his world, where evolution takes place at the cellular level, a new killer is demanding more of his time - antibiotic-resistant bacteria.

Ben is the Director of the Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics. He's been a microbiologist for 30 years but has never been quite so worried by a bug as the one now under his microscope - Acinetobacter baumannii, a potentially deadly antibiotic-resistant bacterium that has appeared in hospitals worldwide.

'It's really amazing that we've only had antibiotics for 70 years or so, since 1941 with penicillin, and are now in a situation where some bacterial infections are untreatable because they're resistant to every known antibiotic. It's scary,' he says.

A.baumanni is among the top six bugs causing infection problems in hospitals. Staphylococcus aureus (golden staph) is another.

Ben is studying A.baumanni in collaboration with Dr John Boyce from the Department of Microbiology and professors Roger Nation and Jian Li at the Monash Institute of Pharmaceutical Sciences.

People catch hospital infections because they're already sick or have their immune system suppressed by treatments, Ben says, and antibiotic-resistant bacteria are more likely to be found in the hospital environment.

But he also blames our excessive, sometimes inappropriate, use of antibiotics to treat human diseases and promote healthy growth in the animals we eat. These practices are slowly disappearing, but they've provided the perfect environment for resistant bacteria to evolve.

'It's evolution on a minute scale,' he says. 'Evolution is simply the environment selecting an individual with an advantage. If antibiotics are in animal feed, the hospital, your throat or your intestine, then mutated bacteria with a selected advantage will flourish - and bacteria are very good at spreading an advantage to other bacteria. Very good indeed.'

Ben's understanding of the genetics of infectious bacteria draws on many years of research into Leptospira, which causes leptospirosis in animals, especially cattle and pigs in Australia, and sometimes farmers, if they come in contact with animal urine. While largely an animal-to-animal disease in Australia, elsewhere it's also a serious zoonosis or animal-to-human disease. In the slums of poor tropical countries, where regular flooding brings residents in contact with rat urine, the mortality rate can be 10 to 20 per cent, mainly because people can't afford treatment.

Penicillin remains effective against leptospirosis in people, if they can afford it, because it's not used to treat the disease in animals, where it's usually found, so the Leptospira bug hasn't developed resistance to it.

It's this knowledge of the genetics of bacteria and how they mutate and evolve that makes Ben's work so valuable in the quest towards finding effective treatments for bacterial infections in animals and humans. He says some 75 per cent of human infectious diseases have animal origins.

He and his team have been funded to investigate how Leptospira causes disease and identify which of its 3000 to 3500 genes are involved. He does this by knocking out some genes to see if that stops or slows the bug's disease-causing ability.

'But Leptospira is a difficult bug,' he says. 'It's only in the last five or six years that we've been able to do that with it.'

Ben works with researchers in France, who developed a similar gene-knockout technique independently, to probe the bug.

His team are also funded to work on fowl cholera, which can devastate poultry farms, and the human disease, melioidosis, a soil-borne disease in northern Australia and South East Asia with a mortality rate of 20 to 50 percent.

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Projects 2000 2013

Research Output 1990 2016

Perturbation of the two-component signal transduction system, BprRS, results in attenuated virulence and motility defects in Burkholderia pseudomallei

Lazar Adler, N. R., Allwood, E. M., Deveson Lucas, D., Harrison, P., Watts, S., Dimitropoulos, A., Treerat, P., Alwis, P., Devenish, R. J., Prescott, M., Govan, B., Adler, B., Harper, M. & Boyce, J. D. 4 May 2016 In : BMC Genomics. 17, 17 p., 331

Research output: Research - peer-reviewArticle

Open Access

Protective efficacy afforded by live Pasteurella multocida vaccines in chickens is independent of lipopolysaccharide outer core structure

Harper, M., John, M., Edmunds, M., Wright, A. A., Ford, M. E., Turni, C., Blackall, P. J., Cox, A. D., Adler, B. & Boyce, J. D. 2016 In : Vaccine. 34, 14, p. 1696 - 1703 8 p.

Research output: Research - peer-reviewArticle

Open Access

What makes a bacterial species pathogenic?: Comparative genomic analysis of the genus Leptospira

Fouts, D. E. , Matthias, M. A. , Adhikarla, H. , Adler, B. , Amorim-Santos, L. , Berg, D. E. , Bulach, D. , Buschiazzo, A. , Chang, Y-F. , Galloway, R. L. , Haake, D. A. , Haft, D. H. , Hartskeerl, R. , Ko, A. I. , Levett, P. N. , Matsunaga, J. , Mechaly, A. E. , Monk, J. M. , Nascimento, A. L. T. , Nelson, K. E. & 9 others Palsson, B., Peacock, S. J., Picardeau, M., Ricaldi, J. N., Thaipandungpanit, J., Wunder Jr., E. A., Yang, X. F., Zhang, J-J. & Vinetz, J. M. 18 Feb 2016 In : PLoS Neglected Tropical Diseases. 10, 2, 57 p., 0004403

Research output: Research - peer-reviewArticle

Open Access
Open Access