Genome structural variation in escherichia coli o157:H7

Stephen F. Fitzgerald*, Nadejda Lupolova, Sharif Shaaban, Timothy J. Dallman, David Greig, Lesley Allison, Sue C. Tongue, Judith Evans, Madeleine K. Henry, Tom N. McNeilly, James L. Bono, David L. Gally

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The human zoonotic pathogen Escherichia coli O157:H7 is defined by its extensive prophage repertoire including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage can enable the generation of large-chromosomal rearrangements (LCRs) by homologous recombination. This work examines the types and frequencies of LCRs across the major lineages of the O157:H7 serotype. We demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157:H7 and by using both optical mapping and Oxford Nanopore long-read sequencing prove that LCRs are generated in laboratory cultures started from a single colony and that these variants can be recovered from colonized cattle. LCRs are biased towards the terminus region of the genome and are bounded by specific prophages that share large regions of sequence homology associated with the recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants indicated that important virulence phenotypes such as Shiga-toxin production, type-3 secretion and motility can be affected by LCRs. In summary, E. coli O157:H7 has acquired multiple prophage regions over time that act to continually produce structural variants of the genome. These findings raise important questions about the significance of this prophage-mediated genome contingency to enhance adaptability between environments.

Original languageEnglish
Article number000682
JournalMicrobial Genomics
Volume7
Issue number11
DOIs
Publication statusPublished - 2021
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge funding from a Food Standards Scotland/Food Standards Agency research grant (FSS101055) along with a BBSRC research grant BB/P02095X/1. We also acknowledge the support from an institute core strategic grant to the Roslin Institute: BBS/E/D/20002173.

Funding Information:
We acknowledge funding from a Food Standards Scotland/Food Standards Agency research grant (FSS101055) along with a BBSRC research grant BB/P02095X/1. We also acknowledge the support from an institute core strategic grant to the Roslin Institute: BBS/E/D/20002173. The authors would like to thank Sandy Fryda-Bradley and the USMARC core sequencing facility for excellent technical assistance. The mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the USDA and does not imply approval to the exclusion of other products that might be suitable. The USDA is an equal opportunity employer and provider.

Publisher Copyright:
© 2021 The Authors.

Keywords

  • Cattle
  • Duplication
  • E. coli
  • Genome structure
  • Inversion
  • O157:H7
  • Optical mapping
  • PFGE
  • Prophage
  • Shiga toxin
  • Type 3 secretion

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