Molecular evolution and population structure of Mycobacterium tuberculosis in Scotland
Molecular techniques were used to explore the population of M. tuberculosis and to study clinical and epidemiological features. Three genetic typing methods were used in this study: SS-PCR (spacer-specific PCR), IS6110 RFLP fingerprints and IS6110 flanking DNA sequence fingerprints, and these were applied to a collection of more than one hundred M. tuberculosis isolates. An analysis of genetic diversity in relation to drug resistance in the study collection showed that there is no clonal relationship between the drug resistant isolates, suggesting that these drug resistant isolates had developed their drug resistances independently. The implication of this finding is that the dissemination of drug resistance by means of primary resistance (strains which are already resistant to one or more drugs) is not a serious problem in Scotland. An analysis of genetic diversity in relation to global geographical distribution suggests that there are predominant clones of M. tuberculosis circulating in Scotland. The implication is that in industrialised countries there may be predominant clones of M. tuberculosis, even although more polymorphism is apparent in the population of M. tuberculosis than in developing countries. More locally, isolates of a certain SS-PCR types were only found in certain health board areas, suggesting that dissemination from person to person may still be occurring in Scotland. To test whether reinfection or reactivation is presently the main reason for tuberculosis in Scotland, an analysis of the distribution and dynamics of genetic markers in different population of M. tuberculosis in terms of patients' age was conducted. This suggested a complex picture whose interpretation was dependent on the relative stability of different genetic markers. The population genetics of polymeric M. tuberculosis genetic markers warrants much future research if they are to be used to understand the evolution of M. tuberculosis.