Complete Genome Sequence of a Francisella tularensis subsp.
            <i>holarctica</i>
            Strain from Germany Causing Lethal Infection in Common Marmosets

Antwerpen, Markus; Schacht, Erik; Kayßer, Philipp; Splettstoesser, Wolf D.

doi:10.1128/genomea.00135-12

Cited by 12 publications

(6 citation statements)

References 7 publications

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“…Several genome sequences of F. tularensis subsp. holarctica are published but only a limited number of genomes has been fully assembled and annotated ( Larsson et al, 2005 , 2009 ; Beckstrom-Sternberg et al, 2007 ; Chaudhuri et al, 2007 ; Rohmer et al, 2007 ; Barabote et al, 2009 ; Champion, 2011 ; Modise et al, 2012 ; Sjodin et al, 2012 ; Svensson et al, 2012 ; Antwerpen et al, 2013 , 2015 ; Atkins et al, 2015 ; Busch et al, 2017 ). The here described assembly is a high quality full genome sequence.…”

Section: Discussionmentioning

confidence: 99%

Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis

et al. 2018

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Francisella (F.) tularensis is a highly virulent, Gram-negative bacterial pathogen and the causative agent of the zoonotic disease tularemia. Here, we generated, analyzed and characterized a high quality circular genome sequence of the F. tularensis subsp. holarctica strain 12T0050 that caused fatal tularemia in a hare. Besides the genomic structure, we focused on the analysis of oriC, unique to the Francisella genus and regulating replication in and outside hosts and the first report on genomic DNA methylation of a Francisella strain. The high quality genome was used to establish and evaluate a diagnostic whole genome sequencing pipeline. A genotyping strategy for F. tularensis was developed using various bioinformatics tools for genotyping. Additionally, whole genome sequences of F. tularensis subsp. holarctica isolates isolated in the years 2008–2015 in Germany were generated. A phylogenetic analysis allowed to determine the genetic relatedness of these isolates and confirmed the highly conserved nature of F. tularensis subsp. holarctica.

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Section: Discussionmentioning

confidence: 99%

Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis

et al. 2018

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“…Genome sequencing has been performed on several F. tularensis and F. novicida strains, with a limited number of genomes fully assembled and annotated (Larsson et al, 2005 ; Beckstrom-Sternberg et al, 2007 ; Chaudhuri et al, 2007 ; Rohmer et al, 2007 ; Barabote et al, 2009 ; Champion et al, 2009 ; Larsson et al, 2009 ; Modise et al, 2012 ; Sjödin et al, 2012 ; Svensson et al, 2012 ; Antwerpen et al, 2013 ). Consistent with the high degree of genetic similarity previously determined via DNA-DNA re-association (Hollis et al, 1989 ), the average nucleotide identity observed across 1.1 MB of genomic sequence from 3 F. novicida strains and 13 F. tularensis strains (8 subsp.…”

Section: Genomicsmentioning

confidence: 99%

Comparative review of Francisella tularensis and Francisella novicida

Kingry

Petersen

2014

Front. Cell. Infect. Microbiol.

176

209

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Francisella tularensis is the causative agent of the acute disease tularemia. Due to its extreme infectivity and ability to cause disease upon inhalation, F. tularensis has been classified as a biothreat agent. Two subspecies of F. tularensis, tularensis and holarctica, are responsible for tularemia in humans. In comparison, the closely related species F. novicida very rarely causes human illness and cases that do occur are associated with patients who are immune compromised or have other underlying health problems. Virulence between F. tularensis and F. novicida also differs in laboratory animals. Despite this varying capacity to cause disease, the two species share ~97% nucleotide identity, with F. novicida commonly used as a laboratory surrogate for F. tularensis. As the F. novicida U112 strain is exempt from U.S. select agent regulations, research studies can be carried out in non-registered laboratories lacking specialized containment facilities required for work with virulent F. tularensis strains. This review is designed to highlight phenotypic (clinical, ecological, virulence, and pathogenic) and genomic differences between F. tularensis and F. novicida that warrant maintaining F. novicida and F. tularensis as separate species. Standardized nomenclature for F. novicida is critical for accurate interpretation of experimental results, limiting clinical confusion between F. novicida and F. tularensis and ensuring treatment efficacy studies utilize virulent F. tularensis strains.

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“…Consistent with the previous observation that Lon predominantly cleaves substrates at the hydrophobic amino acids 29 , 37 , 8 of the 15 Lon substrates were composed of more than 40% nonpolar amino acids (FTL196, FTL578, FTL964, FTL1003, FTL1167, FTL1216, FTL1228, and FTL1935) (Table S4 ). However, this trial did not reveal any obvious biochemical characteristics shared by all of the Lon substrates although they represent an extreme small fraction of the 1800 cellular proteins encoded by the Francisella genomes 46 – 48 .…”

Section: Resultsmentioning

confidence: 72%

Multiple domains of bacterial and human Lon proteases define substrate selectivity

Luo

Yang

et al. 2018

Emerging Microbes & Infections

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The Lon protease selectively degrades abnormal proteins or certain normal proteins in response to environmental and cellular conditions in many prokaryotic and eukaryotic organisms. However, the mechanism(s) behind the substrate selection of normal proteins remains largely unknown. In this study, we identified 10 new substrates of F. tularensis Lon from a total of 21 candidate substrates identified in our previous work, the largest number of novel Lon substrates from a single study. Cross-species degradation of these and other known Lon substrates revealed that human Lon is unable to degrade many bacterial Lon substrates, suggestive of a “organism-adapted” substrate selection mechanism for the natural Lon variants. However, individually replacing the N, A, and P domains of human Lon with the counterparts of bacterial Lon did not enable the human protease to degrade the same bacterial Lon substrates. This result showed that the “organism-adapted” substrate selection depends on multiple domains of the Lon proteases. Further in vitro proteolysis and mass spectrometry analysis revealed a similar substrate cleavage pattern between the bacterial and human Lon variants, which was exemplified by predominant representation of leucine, alanine, and other hydrophobic amino acids at the P(−1) site within the substrates. These observations suggest that the Lon proteases select their substrates at least in part by fine structural matching with the proteins in the same organisms.

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Complete Genome Sequence of a Francisella tularensis subsp. holarctica Strain from Germany Causing Lethal Infection in Common Marmosets

Abstract: Here, we describe the genome sequence of the Francisella tularensis subsp. holarctica strain F92, belonging to the Franco-Iberian subgroup. This strain represents the first-time isolate of this subgroup in Germany and was obtained from naturally infected marmosets.

Cited by 12 publications

References 7 publications

Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis

Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis

Comparative review of Francisella tularensis and Francisella novicida

Multiple domains of bacterial and human Lon proteases define substrate selectivity

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