Samuel J Bloomfield1, Anne C Midwinter2,3, Patrick J Biggs2,3,4, Nigel P French3,5, Jonathan C Marshall2,3,4, David T S Hayman2,3,6, Philip E Carter7, Alison E Mather8,9, Ahmed Fayaz2,3, Craig Thornley10, David J Kelly11, Jackie Benschop2,3. 1. Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK. samuel.bloomfield@quadram.ac.uk. 2. mEpiLab, Hopkirk Research Institute, Massey University, Palmerston North, 4410, New Zealand. 3. Infectious Disease Research Centre, Hopkirk Research Institute, Massey University, Palmerston North, 4410, New Zealand. 4. School of Fundamental Science, Massey University, Palmerston North, 4410, New Zealand. 5. New Zealand Food Safety Science and Research Centre, Hopkirk Research Institute, Massey University, Palmerston North, 4410, New Zealand. 6. Centre of Research Excellence for Complex Systems, Te Pūnaha Matatini, Auckland, New Zealand. 7. Institute of Environmental Science of Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand. 8. Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK. 9. University of East Anglia, Norwich, Norfolk, UK. 10. Regional Public Health, Hutt Hospital, Lower Hutt, 5040, New Zealand. 11. School of Biosciences, The University of Sheffield, Sheffield, South Yorkshire, UK.
Abstract
BACKGROUND: Campylobacter is a genus of bacteria that has been isolated from the gastrointestinal tract of humans and animals, and the environments they inhabit around the world. Campylobacter adapt to new environments by changes in their gene content and expression, but little is known about how they adapt to long-term human colonization. In this study, the genomes of 31 isolates from a New Zealand patient and 22 isolates from a United Kingdom patient belonging to Campylobacter jejuni sequence type 45 (ST45) were compared with 209 ST45 genomes from other sources to identify the mechanisms by which Campylobacter adapts to long-term human colonization. In addition, the New Zealand patient had their microbiota investigated using 16S rRNA metabarcoding, and their level of inflammation and immunosuppression analyzed using biochemical tests, to determine how Campylobacter adapts to a changing gastrointestinal tract. RESULTS: There was some evidence that long-term colonization led to genome degradation, but more evidence that Campylobacter adapted through the accumulation of non-synonymous single nucleotide polymorphisms (SNPs) and frameshifts in genes involved in cell motility, signal transduction and the major outer membrane protein (MOMP). The New Zealand patient also displayed considerable variation in their microbiome, inflammation and immunosuppression over five months, and the Campylobacter collected from this patient could be divided into two subpopulations, the proportion of which correlated with the amount of gastrointestinal inflammation. CONCLUSIONS: This study demonstrates how genomics, phylogenetics, 16S rRNA metabarcoding and biochemical markers can provide insight into how Campylobacter adapts to changing environments within human hosts. This study also demonstrates that long-term human colonization selects for changes in Campylobacter genes involved in cell motility, signal transduction and the MOMP; and that genetically distinct subpopulations of Campylobacter evolve to adapt to the changing gastrointestinal environment.
BACKGROUND: Campylobacter is a genus of bacteria that has been isolated from the gastrointestinal tract of humans and animals, and the environments they inhabit around the world. Campylobacter adapt to new environments by changes in their gene content and expression, but little is known about how they adapt to long-term human colonization. In this study, the genomes of 31 isolates from a New Zealand patient and 22 isolates from a United Kingdom patient belonging to Campylobacter jejuni sequence type 45 (ST45) were compared with 209 ST45 genomes from other sources to identify the mechanisms by which Campylobacter adapts to long-term human colonization. In addition, the New Zealand patient had their microbiota investigated using 16S rRNA metabarcoding, and their level of inflammation and immunosuppression analyzed using biochemical tests, to determine how Campylobacter adapts to a changing gastrointestinal tract. RESULTS: There was some evidence that long-term colonization led to genome degradation, but more evidence that Campylobacter adapted through the accumulation of non-synonymous single nucleotide polymorphisms (SNPs) and frameshifts in genes involved in cell motility, signal transduction and the major outer membrane protein (MOMP). The New Zealand patient also displayed considerable variation in their microbiome, inflammation and immunosuppression over five months, and the Campylobacter collected from this patient could be divided into two subpopulations, the proportion of which correlated with the amount of gastrointestinal inflammation. CONCLUSIONS: This study demonstrates how genomics, phylogenetics, 16S rRNA metabarcoding and biochemical markers can provide insight into how Campylobacter adapts to changing environments within human hosts. This study also demonstrates that long-term human colonization selects for changes in Campylobacter genes involved in cell motility, signal transduction and the MOMP; and that genetically distinct subpopulations of Campylobacter evolve to adapt to the changing gastrointestinal environment.
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