Location: Meat Safety and QualityTitle: Genome structural variation in Escherichia coli O157:H7
|FITZGERALD, STEPHEN - Roslin Institute|
|LUPOLOVA, NADEJDA - Roslin Institute|
|SHAABAN, SHARIF - Roslin Institute|
|DALLMAN, TIMOTHY - Public Health England (PHE)|
|GREIG, DAVID - Public Health England (PHE)|
|ALLISON, LESLEY - National Health Service Scotland, Health Protection Scotland|
|TONGUE, SUE - Sruc-Scotland'S Rural College|
|EVANS, JUDITH - Sruc-Scotland'S Rural College|
|HENRY, MADELEINE - Sruc-Scotland'S Rural College|
|MCNEILLY, TOM - Moredon Research Institute|
|Bono, James - Jim|
|GALLY, DAVID - Roslin Institute|
Submitted to: Microbial Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/2021
Publication Date: 11/9/2021
Citation: Fitzgerald, S., Lupolova, N., Shaaban, S., Dallman, T.J., Greig, D.Q., Allison, L., Tongue, S.C., Evans, J., Henry, M.K., McNeilly, T., Bono, J.L., Gally, D.L. 2021. Genome structural variation in Escherichia coli O157:H7. Microbial Genomics. 7(11). Article 000682. https://doi.org/10.1099/mgen.0.000682.
Interpretive Summary: Shiga toxin-containing Escherichia coli O157:H7 (STEC O157) is a bacterium that can cause diarrhea, bloody diarrhea, and kidney failure in humans. Zoonotic infections with STEC O157 have emerged as a serious threat to human health in the last three decades. Cattle are a natural reservoir for STEC O157 strains. However, it also survives in environments outside the gut. There are different ways that STEC O157 can adapt to changes in its environment, with one of them occurring as a rearrangement of the chromosome where a section can be inverted. This study determined that large chromosomal rearrangements were common in STEC O157 and these variants can give the bacteria altered phenotypes, such as increased motility or toxin production, that allows them to adapt to a specific environment. This mechanism is another way bacteria can generate variations in the population without changing their overall gene content.
Technical 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.