Phylogeography of Bacillus anthracis in the Country of Georgia Shows Evidence of Population Structuring and Is Dissimilar to Other Regional Genotypes

Khmaladze, Ekaterine; Birdsell, Dawn N.; Naumann, Amber; Hochhalter, Christian B.; Seymour, Meagan L.; Nottingham, Roxanne; Beckstrom-Sternberg, Stephen M.; Beckstrom-Sternberg, James; Nikolich, Mikeljon P.; Chanturia, Gvantsa; Zhgenti, Ekaterine; Zakalashvili, Mariam; Malania, Lile; Babuadze, Giorgi; Tsertsvadze, Nikoloz; Abazashvili, Natalia; Kekelidze, Merab; Tsanava, Shota; Imnadze, Paata; Ganz, Holly H.; Getz, Wayne M.; Pearson, Ofori N.; Gajer, Pawel; Eppinger, Mark; Wagner, David M.; Okinaka, Richard T.; Schupp, James M.; Keim, Paul; Pearson, Talima

doi:10.1371/journal.pone.0102651

Cited by 19 publications

(38 citation statements)

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“…Although distinct, the two subclades are closely related with only 16 SNPs separating them. This level of variation is frequently seen within a single country ( Khmaladze et al, 2014 , Simonson et al, 2009 , Kenefic et al, 2009 ) and could be indicative of a close geographic relationship for the two sources.…”

Section: Discussionmentioning

confidence: 78%

Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

et al. 2015

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BackgroundAnthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. Injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple European countries and this outbreak has been difficult to trace back to a source.MethodsWe took a molecular epidemiological approach in understanding this disease outbreak, including whole genome sequencing of Bacillus anthracis isolates from the anthrax victims. We also screened two large strain repositories for closely related strains to provide context to the outbreak.FindingsAnalyzing 60 Bacillus anthracis isolates associated with injectional anthrax cases and closely related reference strains, we identified 1071 Single Nucleotide Polymorphisms (SNPs). The synapomorphic SNPs (350) were used to reconstruct phylogenetic relationships, infer likely epidemiological sources and explore the dynamics of evolving pathogen populations. Injectional anthrax genomes separated into two tight clusters: one group was exclusively associated with the 2009–10 outbreak and located primarily in Scotland, whereas the second comprised more recent (2012–13) cases but also a single Norwegian case from 2000.InterpretationGenome-based differentiation of injectional anthrax isolates argues for at least two separate disease events spanning > 12 years. The genomic similarity of the two clusters makes it likely that they are caused by separate contamination events originating from the same geographic region and perhaps the same site of drug manufacturing or processing. Pathogen diversity within single patients challenges assumptions concerning population dynamics of infecting B. anthracis and host defensive barriers for injectional anthrax.FundingThis work was supported by the United States Department of Homeland Security grant no. HSHQDC-10-C-00,139 and via a binational cooperative agreement between the United States Government and the Government of Germany. This work was supported by funds from the German Ministry of Defense (Sonderforschungsprojekt 25Z1-S-431,214). Support for sequencing was also obtained from Illumina, Inc. These sources had no role in the data generation or interpretation, and had not role in the manuscript preparation.Panel 1: Research in Context Systematic ReviewWe searched PubMed for any article published before Jun. 17, 2015, with the terms “Bacillus anthracis” and “heroin”, or “injectional anthrax”. Other than our previously published work (Price et al., 2012), we found no other relevant studies on elucidating the global phylogenetic relationships of B. anthracis strains associated with injectional anthrax caused by recreational heroin consumption of spore-contaminated drug. There were, however, publically available genome sequences of two strains involved (Price et al., 2012, Grunow et al., 2013) and the draft genome sequence of Bacillus anthracis UR-1, isolated from a German heroin user (Ruckert et al., 2012) with only limited information on the genotyping of closely relat...

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Section: Discussionmentioning

confidence: 78%

Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

et al. 2015

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“…This technique categorizes isolates into one of 12 sub-lineages (C.Br.A1055, B.Br.CNEVA, B.Br.KrugerB, A.Br.Vollum, A.Br.Aust94, A.Br.Ames, A.Br.WNA, B.Br.001/002, A.Br.005/006, A.Br.003/004, A.Br.001/002, A.Br.008/009). Additional canSNP that provides resolution within the A.Br.008/009, A.Br.001/002, A.Br.Ames and A.Br.Aust94 groups were also used [ 10 , 14 , 18 , 20 – 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…In a continued effort to acquire and molecularly subtype isolates from around the world, other SNPs that define further the population structure of some lineages and groups or that lie on various branches of the B . anthracis SNP tree have also been identified [ 14 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

Whole Genome-Sequencing and Phylogenetic Analysis of a Historical Collection of Bacillus anthracis Strains from Danish Cattle

et al. 2015

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Bacillus anthracis, the causative agent of anthrax, is known as one of the most genetically monomorphic species. Canonical single-nucleotide polymorphism (SNP) typing and whole-genome sequencing were used to investigate the molecular diversity of eleven B. anthracis strains isolated from cattle in Denmark between 1935 and 1988. Danish strains were assigned into five canSNP groups or lineages, i.e. A.Br.001/002 (n = 4), A.Br.Ames (n = 2), A.Br.008/011 (n = 2), A.Br.005/006 (n = 2) and A.Br.Aust94 (n = 1). The match with the A.Br.Ames lineage is of particular interest as the occurrence of such lineage in Europe is demonstrated for the first time, filling an historical gap within the phylogeography of the lineage. Comparative genome analyses of these strains with 41 isolates from other parts of the world revealed that the two Danish A.Br.008/011 strains were related to the heroin-associated strains responsible for outbreaks of injection anthrax in drug users in Europe. Eight novel diagnostic SNPs that specifically discriminate the different sub-groups of Danish strains were identified and developed into PCR-based genotyping assays.

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“…Such a spread of related strains over vast geographic distances seems not to be uncommon for B. anthracis as evidenced by the A.Br.013/015 node which is basal to the Aust94 lineage. This A.Br.013/015 node and its expansion comprise isolates from the countries of Georgia, Europe and the U.S.A. (Khmaladze et al, 2014). The authors deduced from their data that the A.Br.013/015 node is not ecologically established in Europe and the USA.…”

Section: Epidemiological Analysis Suggests Historic Importation Of Bmentioning

confidence: 96%

“…This is due in part, because meta-data on the origins of older European strains are often fragmentary and MLVA-data for individual markers (MLVA-31) of many strains in collections are largely not published (Derzelle and Thierry, 2013;Girault et al, 2014a;Girault et al, 2014c). Similarly, it has been proposed that the presence of the A.Br.013/015 node which leads to the Aust94 branch, in Europe, the U.S.A. and possibly Georgia and Turkey actually originated from the importation of contaminated animal products (Khmaladze et al, 2014).…”

Section: Epidemiological Analysis Suggests Historic Importation Of Bmentioning

confidence: 99%

Unexpected genomic relationships between Bacillus anthracis strains from Bangladesh and Central Europe

Rume

Ahsan

Biswas

et al. 2016

Infection, Genetics and Evolution

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The zoonosis anthrax caused by the bacterium Bacillus anthracis has a broad geographical distribution. Active enzootic areas are typically located away from central and northern Europe where cases of the disease occur only sporadically and in limited numbers. In contrast, a few out of the 64 districts of Bangladesh are hyper-endemic for anthrax and there the disease causes major losses in live-stock. In this study we genotyped eight strains of B. anthracis collected from the districts of Sirajganj and Tangail in 2013. All these strains belonged to canSNP group A.Br.001/002 Sterne differing only in a few of 31 tandem-repeat (MLVA)-markers. Whole genome sequences were obtained from five of these strains and compared with genomic information of B. anthracis strains originating from various geographical locations. Characteristic signatures were detected defining two "Bangladesh" clusters potentially useful for rapid molecular epidemiology. From this data high-resolution PCR assays were developed and subsequently tested on additional isolates from Bangladesh and Central Europe. Remarkably, this comparative genomic analysis focusing on SNP-discovery revealed a close genetic relationship between these strains from Bangladesh and historic strains collected between 1991 and 2008 in The Netherlands and Germany, respectively. Possible explanations for these phylogenetic relationships are discussed.

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Phylogeography of Bacillus anthracis in the Country of Georgia Shows Evidence of Population Structuring and Is Dissimilar to Other Regional Genotypes

Cited by 19 publications

References 12 publications

Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

Whole Genome-Sequencing and Phylogenetic Analysis of a Historical Collection of Bacillus anthracis Strains from Danish Cattle

Unexpected genomic relationships between Bacillus anthracis strains from Bangladesh and Central Europe

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