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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Meat Safety and Quality » Research » Publications at this Location » Publication #381088

Research Project: Genomic and Metagenomic Differences in Foodborne Pathogens and Determination of Ecological Niches and Reservoirs

Location: Meat Safety and Quality

Title: Prophage-dependent recombination drives genome structural variation and phenotypic heterogeneity in Escherichia coil O157:H7

item FITZGERALD, STEPHEN - Roslin Institute
item LUPOLOVA, NADEJDA - Roslin Institute
item SHAABAN, SHARIF - Roslin Institute
item DALLMAN, TIMOTHY - Public Health England (PHE)
item GREIG, DAVID - Public Health England (PHE)
item ALLISON, LESLEY - National Health Service Scotland, Health Protection Scotland
item TONGUE, SUE - Sruc-Scotland'S Rural College
item EVANS, JUDITH - Sruc-Scotland'S Rural College
item HENRY, MADELEINE - Sruc-Scotland'S Rural College
item MCNEILLY, TOM - The Moredun Group
item Bono, James - Jim
item GALLY, DAVID - Roslin Institute

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 12/2/2020
Publication Date: 12/2/2020
Citation: Fitzgerald, S.F., Lupolova, N., Shaaban, S., Dallman, T.J., Greig, D., Allison, L., Tongue, S.C., Evans, J., Henry, M.K., McNeilly, T.N., Bono, J.L., Gally, D.L. 2020. Prophage-dependent recombination drives genome structural variation and phenotypic heterogeneity in Escherichia coil O157:H7. bioRxiv. 407981.

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 is defined by its extensive prophage repertoire 3 including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology 4 in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage 5 can enable the generation of large-chromosomal rearrangements (LCRs) by homologous 6 recombination. This work examines the types and frequencies of LCRs across the major lineages of 7 the O157 serogroup and defines the phenotypic consequences of specific structural variants. We 8 demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157 9 and by using both optical mapping and ONT long-read sequencing demonstrate that LCRs are 10 generated in laboratory cultures started from a single colony and particular variants are selected 11 during animal colonisation. LCRs are biased towards the terminus region of the genome and are 12 bounded by specific prophages that share large regions of sequence homology associated with the 13 recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants 14 indicated that important virulence phenotypes such as Shiga toxin production, type 3 secretion and 15 motility are affected by LCRs. In summary, E. coli O157 has acquired multiple prophage regions 16 over time that act as genome engineers to continually produce structural variants of the genome. 17 This structural variation is a form of epigenetic regulation that generates sub-population phenotypic 18 heterogeneity with important implications for bacterial adaptation and survival.