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Title: Comparative genomic analyses reveal broad diversity in botulinum-toxin-producing Clostridia

Journal Article · · BMC Genomics
 [1];  [1];  [2];  [3];  [4];  [5];  [6];  [7];  [7];  [1];  [1];  [3]
  1. Northern Arizona Univ., Flagstaff, AZ (United States). Center for Microbial Genetics and Genomics
  2. US Army Medical Research Inst. of Infectious Diseases, Fort Detrick, MD (United States)
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Div.
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Div.
  5. US Army Medical Research Inst of Infecgious Diseases, Fort Detrick, MD (United States). Medical Countermeasures Technology, US Army Medical Research and Material Command
  6. Área Microbiología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Centro Universitario, Mendoza (Argentina)
  7. Univ. of Helsinki (Finland). Dept. of Food Hygiene and Environmental Health

Background: Clostridium botulinum is a diverse group of bacteria characterized by the production of botulinum neurotoxin. Botulinum neurotoxins are classified into serotypes (BoNT/A–G), which are produced by six species/Groups of Clostridia, but the genetic background of the bacteria remains poorly understood. The purpose of this study was to use comparative genomics to provide insights into the genetic diversity and evolutionary history of bacteria that produce the potent botulinum neurotoxin. Results: Comparative genomic analyses of over 170 Clostridia genomes, including our draft genome assemblies for 59 newly sequenced Clostridia strains from six continents and publicly available genomic data, provided in-depth insights into the diversity and distribution of BoNT-producing bacteria. These newly sequenced strains included Group I and II strains that express BoNT/A,/B,/E, or/F as well as bivalent strains. BoNT-producing Clostridia and closely related Clostridia species were delineated with a variety of methods including 16S rRNA gene, concatenated marker genes, core genome and concatenated multi-locus sequencing typing (MLST) gene phylogenies that related whole genome sequenced strains to publicly available strains and sequence types. These analyses illustrated the phylogenetic diversity in each Group and the diversity of genomic backgrounds that express the same toxin type or subtype. Comparisons of the botulinum neurotoxin genes did not identify novel toxin types or variants. Conclusions: This study represents one of the most comprehensive analyses of whole genome sequence data for Group I and II BoNT-producing strains. Read data and draft genome assemblies generated for 59 isolates will be a resource to the research community. Core genome phylogenies proved to be a powerful tool for differentiating BoNT-producing strains and can provide a framework for the study of these bacteria. Comparative genomic analyses of Clostridia species illustrate the diversity of botulinum-neurotoxin-producing strains and the plasticity of the genomic backgrounds in which bont genes are found.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE; U.S. Department of Homeland Security
Grant/Contract Number:
AC52-06NA25396; HSHQDC-10-C-00139; DHS-2010-ST-108-000019
OSTI ID:
1626797
Journal Information:
BMC Genomics, Vol. 17, Issue 1; ISSN 1471-2164
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English

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An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production journal November 2016
Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature journal January 2017
Diversity of Group I and II Clostridium botulinum Strains from France Including Recently Identified Subtypes journal April 2016
Differentiating Botulinum Neurotoxin-Producing Clostridia with a Simple, Multiplex PCR Assay journal July 2017
Diversity of the Germination Apparatus in Clostridium botulinum Groups I, II, III, and IV journal October 2016
Optimization of SNAP-25 and VAMP-2 Cleavage by Botulinum Neurotoxin Serotypes A–F Employing Taguchi Design-of-Experiments journal October 2019
Botulinum neurotoxin–encoding plasmids can be conjugatively transferred to diverse clostridial strains journal February 2018
Genomic insights into the evolution and ecology of botulinum neurotoxins journal April 2018
Reoccurrence of botulinum neurotoxin subtype A3 inducing food-borne botulism, Slovakia, 2015 journal August 2017
Genetic Characterization of the Exceptionally High Heat Resistance of the Non-toxic Surrogate Clostridium sporogenes PA 3679 journal April 2017
Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip journal May 2018
Botulinum Neurotoxin Detection Methods for Public Health Response and Surveillance journal June 2018
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