Genomic Analysis of Bacterial Outbreaks

The study of outbreaks of infectious diseases has been revolutionized by the current availability of fast and efficient, high-throughput methods capable of yielding the nucleotide sequence of complete genomes of viruses and bacteria within a few days, or even hours. These methods are replacing previous molecular techniques which have been used for the past 30 years, although many of them are still the usual approach for many such investigations. Here we review the major technologies currently in use for high-throughput sequencing of bacterial genomes emphasizing their advantages and drawbacks for the analysis of outbreaks. The use of more efficient methods does not necessarily mean that all the problems in the study of outbreaks are automatically solved. In fact, because these methods are capable of revealing genetic variation at an unprecedented level and scale they also pose new challenges for the interpretation of the resulting data. We analyze some of these new challenges, especially those in which the short term evolution of microorganism plays an important role in understanding and interpreting the results and, quite often, in reconciling them with those derived from classical epidemiological analyses. Finally, we exemplify the advantages of using complete genome analysis with two cases, involving outbreaks of Mycobacterium tuberculosis and Legionella pneumophila.