Invasiveness of bacteria pathogens in Gambian children

The ability to tell which bacteria are most likely to cause disease and kill humans is very important for treatment, tracking these bacteria and to vaccine development. We now use a new method called multilocus sequence typing (MLST) to do so. MLST unambiguously characterises bacterial strains using its genetic material. Most MLST studies done so far have focused on bacteria isolated in the USA and Europe although most bacterial disease occurs in the developing world; therefore, the identity of a lot of disease causing bacteria from Africa is unknown. This is crucial in terms of future vaccine development in Africa as one need to know what types of bacteria strains to target in a vaccine. We therefore propose to undertake a detailed MLST study on bacterial isolates from The Gambia and determine which bacterial clones are more likely to cause invasive disease in The Gambia. We will then compare strains causing disproportionately more invasive disease with strains less likely associated with invasive disease and with global isolates at the genetic level.

The ability to distinguish accurately between different strains within a bacterial species is key to disease treatment, epidemiological surveillance and to vaccine development. Until recently the methods that were used to characterise bacterial isolates were unsatisfactory as they indexed genetic variation that was difficult to compare between laboratories. A new approach; multilocus sequence typing (MLST) unambiguously characterises isolates of bacterial pathogens using the nucleotide sequences of internal fragments of seven house-keeping genes scattered roughly equally around the circular bacterial chromosome. Most MLST studies thus far have focused on bacteria isolated in the USA and Europe although most bacterial disease occurs in the developing world; hence a considerable portion of the global diversity of bacterial pathogens is unexplored. This is crucial in terms of future vaccine development in Africa as one needs to know what types of strains or serotypes to target in a vaccine, because different geographical regions may harbour different clonal groupings and different clonal groupings may predominate at different periods of time. We therefore propose to undertake a detailed MLST study on bacterial isolates and determine which bacterial clones are more likely to cause invasive disease in The Gambia. We will then compare strains causing disproportionately more invasive disease with strains less likely associated with invasive disease and with global isolates at the genetic level.