Genomic epidemiology of a respiratory tularemia outbreak

For agents of concern in bioterrorism, such as Francisella tularensis, knowledge on the genetic diversity of strains occurring in natural outbreaks is of special interest. An outbreak of respiratory tularemia type B occurred in Jämtland county, Sweden. F. tularensis was isolated from blood or pleural fluid of ten humans living in various parts of the county. Single nucleotide polymorphism (SNPs) across the genomes, genetic similarities among the isolates were measured and compared also with 110 historic isolates derived from various parts of the world. The genomes of ten outbreak isolates and the 25 most closely related historic isolates, all derived from various parts of Sweden had 1,568,083 shared nucleotide positions and 757 SNPs. The outbreak genomes clustered into three distinct genetic clades. Extreme sequence similarity, in some cases identical genomes, linked outbreak and historic isolates originating from patients in distant geographical regions and up to ten years earlier. The outbreak was caused by genetically diverse F. tularensis sources from multiple localities. The pattern of genetic diversity contradicts an explanation based on single wave replication of outbreak-specific strains. The genetic pattern in natural occurrence of respiratory tularemia should be expected to be quite different from an outbreak due to intentional spread of F. tularensis.