An Outbreak of Respiratory Tularemia Caused by Diverse Clones of Francisella tularensis

Johansson, Anders; Lärkeryd, Adrian; Widerström, Micael; Mörtberg, Sara; Myrtännäs, Kerstin; Öhrman, Caroline; Birdsell, Dawn N.; Keim, Paul; Wagner, David M.; Forsman, Mats; Larsson, Pär

doi:10.1093/cid/ciu621

Cited by 51 publications

(57 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings are in analogy with those reported in a recent genomic study of a respiratory tularaemia outbreak in Sweden [30]. In the latter study it was shown that the respiratory form of tularaemia was not tied to specific genotypes of F. tularensis and that outbreak genomes shared high sequence similarity with archived isolates originating from patients from distant geographical regions and collected up to 10 years apart [30]. Despite the mentioned lack of significant association in our study, it is worth noting that F. tularensis of clade B.12 was found mainly in patients with ulceroglandular tularaemia, and that all three isolates from patients with typhoidal tularaemia belonged to subclade B.7 (Table).…”

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

“…An alternative explanation may be that identical genotypes of F. tularensis have evolved by parallel evolution in many geographical regions of the Scandinavian Peninsula. Our results may be consistent with a life cycle of the bacterium that includes a state of quiescence (absence or very low level of replication) for long periods of time between outbreaks [30,31].…”

Section: Discussionsupporting

confidence: 88%

See 2 more Smart Citations

Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011

et al. 2015

View full text Add to dashboard Cite

In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Second, there are no data on generation times or mutation rates in environmental B. pseudomallei strains, with evolution and doubling rates likely to vastly differ from those of in vitro-or mammalian-passaged strains. This issue of different generation times has recently been exemplified in an outbreak of Francisella tularensis (tularemia) in Sweden, where no correlations between spatial, temporal, and genetic distances were found (46). Third, there is insufficient resolution among the Australian ST-562 genomes, as evidenced by several polytomies in our ST-562 phylogenies (see Fig.…”

Section: Discussionmentioning

confidence: 89%

Unprecedented Melioidosis Cases in Northern Australia Caused by an Asian Burkholderia pseudomallei Strain Identified by Using Large-Scale Comparative Genomics

Price

Sarovich

Smith

et al. 2016

Appl Environ Microbiol

Self Cite

View full text Add to dashboard Cite

Melioidosis is a disease of humans and animals that is caused by the saprophytic bacterium Burkholderia pseudomallei. Once thought to be confined to certain locations, the known presence of B. pseudomallei is expanding as more regions of endemicity are uncovered. There is no vaccine for melioidosis, and even with antibiotic administration, the mortality rate is as high as 40% in some regions that are endemic for the infection. Despite high levels of recombination, phylogenetic reconstruction of B. pseudomallei populations using whole-genome sequencing (WGS) has revealed surprisingly robust biogeographic separation between isolates from Australia and Asia. T he Gram-negative soil-dwelling bacterium Burkholderia pseudomallei is the etiologic agent of melioidosis, an often deadly tropical disease that can be difficult to diagnose, particularly in nonendemic or resource-poor regions where cases are not expected and appropriate microbiological diagnostic tools are not readily available (1). Diabetics are particularly susceptible to melioidosis. B. pseudomallei infection can be acquired from contaminated soil or water by percutaneous inoculation, inhalation, aspiration, or ingestion, and no vaccine targeting this organism is available (2). In 2012, B. pseudomallei was reclassified by U.S. federal agencies as a tier 1 select agent, the highest risk category for a biological entity, due to concerns that this bacterium would pose a severe threat to humans and animals in the event of its deliberate misuse (3).The B. pseudomallei genome exhibits high homologous recombination rates. On a per-allele basis, recombination is estimated to occur between 18 and 30 times more frequently than mutation (4). This extensive lateral gene transfer can confound population analyses, particularly those that are based on studying limited geographic regions (e.g., the Northern Territory, Australia [5]) due to high rates of homoplasy observed among genetic variants. In contrast, genomic analyses of B. pseudomallei populations on a continental scale have revealed a clear separation of B. pseudomallei isolates between Asia and Australia (4, 6, 7). Bayesian analysis of B. pseudomallei genome variation points to an ancient separation, with migration out of Australia into Asia occurring tens of thousands of years ago during the Pleistocene (4). The rarity of pathogen movement is due largely to one factor: new melioidosis cases almost always result from bacterial infection acquired from the local environment, with human-to-human and zoonotic transmission of this pathogen being exceedingly rare (8). In support of the rarity of B. pseudomallei movement across major biogeographic boundaries, the definitive transmission of B. pseudomallei from Asia into Australia has not yet been observed. Nevertheless, melioidosis cases imported into nonendemic locations via travelers are being increasingly reported, as is recognition of locations that are endemic for melioidosis outside the classical regions of Southeast Asia and Australia (9). With modern global tra...

show abstract

“…It was not until November 1997 that a new tularemia focus appeared and new F. tularensis strains were isolated in Bulgaria. Recent genomic epidemiological studies of tularemia in Sweden and Norway have revealed strains that are almost 100% identical at the genome level despite being isolated many years apart and/or separated by several hundreds of km (8, 9). In light of these findings, we asked if the clone/clones that caused the recent epidemics in Bulgaria were the same as those that occurred in the early 1960s.…”

mentioning

confidence: 99%

Introduction and persistence of tularemia in Bulgaria

Myrtennäs

Marinov

Johansson

et al. 2016

Infection Ecology & Epidemiology

Self Cite

View full text Add to dashboard Cite

IntroductionOutbreaks of the zoonotic disease tularemia occurred in north-east Bulgaria in the 1960s. Then came 30 years of epidemiological silence until new outbreaks occurred in west Bulgaria in the 1990s. To investigate how bacterial strains of Francisella tularensis causing tularemia in wildlife and humans in the 1960s and the 1990s were related, we explored their genetic diversity.Material and methodsTen F. tularensis genomes from the 1960s (n=3) and the 1990s (n=7) were sequenced, assigned to canonical single-nucleotide polymorphism (canSNP) clades, and compared to reference genomes. We developed four new canSNP polymerase chain reaction (PCR) assays based on the genome sequence information.Results and discussionThe genetic analysis showed that the outbreaks in the 1960s as well as in the 1990s involved multiple clones and new genetic diversity. The smallest genetic difference found between any of the Bulgarian strains was five SNPs between the strains L2 and 81 isolated 43 years apart, indicating that F. tularensis may persist locally over long time periods without causing outbreaks. The existence of genetically highly similar strain-pairs isolated the same year in the same area from different hosts supports a hypothesis of local expansion of clones during outbreaks. Close relationship (two SNPs) was found between one strain isolated 1961 in northeast Bulgaria and one strain isolated 5 years before in USSR. Historical data coinciding with the actual time point describe the introduction of water rats from USSR into the Bulgarian outbreak area, which may explain the close genetic relationship and the origin of the outbreak.ConclusionGenome analysis of strains from two outbreaks in the 1960s and the 1990s provided valuable information on the genetic diversity and persistence of F. tularensis in Bulgaria.

show abstract

An Outbreak of Respiratory Tularemia Caused by Diverse Clones of Francisella tularensis

Cited by 51 publications

References 39 publications

Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011

Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011

Unprecedented Melioidosis Cases in Northern Australia Caused by an Asian Burkholderia pseudomallei Strain Identified by Using Large-Scale Comparative Genomics

Introduction and persistence of tularemia in Bulgaria

Contact Info

Product

Resources

About