DNA databases tapped for typhoid clues

Using international DNA databases, a University of Melbourne PhD student has discovered a variety of previously anonymous bacteria in the mammalian gut that may explain why live oral vaccines against bacterial diseases like typhoid fever often produce erratic results.

Maja Galic, a researcher with the Cooperative Research Centre for Vaccine Technology, believes the protective effect of live oral vaccines for humans could be significantly improved by modifying the gut flora.

Galic says the weakened strains of pathogenic microbes used in live oral vaccines -- Salmonella typhi, in the case of typhoid fever -- must interact with resident, communal microbes in the intestinal tract.

Only about 40 per cent of bacteria species that inhabit the human gut have been identified; the rest have remained anonymous because they are anaerobic, and their nutrient requirements are unknown, making them very difficult to culture in the laboratory.

Galic is a member of a Vaccine Technology CRC team that is studying whether altering the composition of the microbial population of the gut enhances their response to oral vaccines.

She and her colleagues have identified a host of new bacterial species, and are investigating whether any of them play significant roles in protecting against Salmonella protection.

In a mouse model, the CRCVT researchers have found intestinal microfloras vary markedly between individuals and groups, presumably because of a combination of diet, the individual's genetic makeup, and the fact that chance has a large role in determining which microbes colonise the gut.

The researchers have been trying to determine of the composition of an individual's commensal microflora determines how well -- or poorly -- they respond to oral vaccines.

Galic said new bacteria entering the intestine, whether benign or pathogenic, had to compete with resident commensal microbes for living room and access to nutrients.

Pathogenic Salmonella could only cause serious disease if they successfully spread to other organs, like the spleen and liver, after surviving confrontation with the resident intestinal microflora.

In experiments in mice, the researchers found that mice treated with antibiotics subsequently became much more susceptible to infection by pathogenic Salmonella.

Galic said her identification of a host of new, albeit probably benign, species of bacteria in the gut, including new anaerobic species like Lactobacillus, was relevant both to the use of antibiotics to treat bacterial infections, and to augment the efficacy of oral vaccines.

It was likely some of the more dominant species in the anonymous horde were reducing the efficacy of oral vaccines by out-competing their weakened Salmonella strains. If such vaccines were administered after antibiotic treatment, they might elicit a more protective immune response.