Genome solved -- hunt for vaccine targets begins

The genes of a bacterium that can kill or cause permanent organ damage in humans have been identified by Monash University researchers, whose efforts are now focused on finding a suitable vaccine.

Professor Ben Adler from the Department of Microbiology led Australia's first bacterial genome project that has identified the genes of the bacterium Leptospira. The team has now begun work on finding targets for a vaccine against Leptospira, which causes the disease leptospirosis.

"Leptospirosis is an infection of some importance both around the world and in Australia, especially in farming communities," Prof. Adler said. The disease is transmitted to humans by animals and in Australia typically causes influenza-like symptoms and high fever.

There are estimated to be one million cases of leptospirosis worldwide each year. Although in Australia the disease is rarely fatal, mortality rates in developing countries can be as high as 20%. Workers who have contact with animals are at highest risk - in Australia leptospirosis is most common among dairy and pig farmers and banana plantation workers who are infected through contact with rat urine.

Most mammals have co-evolved with species-specific strains, or serovars, of Leptospira. The hosts can have no symptoms but still transmit these strains to humans. Prof. Adler worked with researchers at the US Department of Agriculture and the Australian Genome Research Facility to determine the genetic sequences of two strains of the Hardjo serovar of Leptospira, the serovar common to Australia.

The team used the bacterium's genetic sequence to identify individual genes but then, using scripts and programs designed by the Victorian Bioinformatics Consortium to process the data, they ascribed a function to each gene.

More than 3000 genes were identified over the bacterium's two circular chromosomes - 3111 genes on the large chromosome and 292 on the small one.

Efforts to develop a vaccine against Leptospira have been frustrated by the diversity of its main antigens (the sugar components on the outer membrane of the bacterium).

"These proteins of the outer membrane interact with the host, whether it's human or animal, and are targets for antibiotics as well as potential vaccine candidates," Prof. Adler said. "Without a genome sequence, we just tried to find proteins that might be on the outer membrane of the organism and might play a role in stimulating immunity," he said. "By knowing every single gene that the organism has, we can predict which genes produce the antigens that are potentially important in immunity.

The Leptospira vaccines that exist at the moment are not suitable for humans and are only effective against individual serovars. "With the genome, we can find surface proteins that are common to all serovars of Leptospira and use these as the basis for a single vaccine," Prof. Adler said.

Item provided courtesy of Monash University