Microbial pathogens: from Ecology to Synthetic Biology
Lead Research Organisation:
QUADRAM INSTITUTE BIOSCIENCE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Objectives: to understand microbial communities and to exploit synthetic biology to turn E. coli into a smart probiotic capable of improving such communities. We have investigated the ecology of complex microbial communities using high-throughput sequencing on the Illumina platform in two settings: the gut microbiome in critically ill patients from the UK (focusing on drug-resistant pathogens) and the gut microbiome in ticks (focusing on potential vertebrate pathogens and tick endosymbionts). The establishment of laboratory and bioinformatics workflows have allowed us to document the changes in the microbial ecology of adult critically ill trauma patients during their stay in the Intensive Care Unit at the Queen Elizabeth Hospital in Birmingham, performing shotgun metagenomic sequencing of serial faecal samples. We have also cultured E. coli isolates from these samples and genome-sequenced multiple colony-picks to investigate within-host diversity and ecology and evolution for this important organism. On ticks from Palestine, we have employed a two-stage surveillance protocol, initially screening pools of ticks using 16S rRNA sequencing, followed by shotgun metagenomics to investigate genomic diversity and population structure of microbes from the tick gut. We have detected and characterised a range potential pathogens or endosymbionts in ticks, including representatives of the genera Rickettsia, Anaplasma, Francisella and Coxiella. In pursuit of our goal of re-engineering E. coli, we have focused on the bacterial flagellum as a tool for surface display of enzymes and other globular proteins. To determine the constraints to the size of flagellin, we have carried out and published a survey of natural diversity in the size of flagellins and flagellar filaments. We have also created constructs needed for expression of flagellins incorporating enzymatic domains in E. coli and shown that hybrid flagellins can be used to express enzymatic activity.
Planned Impact
unavailable
Publications
Callanan J
(2021)
Leviviricetes: expanding and restructuring the taxonomy of bacteria-infecting single-stranded RNA viruses.
in Microbial genomics
Crossfield M
(2022)
Archaeal and Bacterial Metagenome-Assembled Genome Sequences Derived from Pig Feces.
in Microbiology resource announcements
Foster-Nyarko E
(2022)
The microbial ecology of Escherichia coli in the vertebrate gut.
in FEMS microbiology reviews
Foster-Nyarko E
(2020)
Genomic diversity of Escherichia coli isolates from non-human primates in the Gambia.
in Microbial genomics
Foster-Nyarko E
(2020)
Gambian poultry isolates from hyperendemic group of AMR Escherichia coli strains in sub-Saharan Africa
in Access Microbiology
Foster-Nyarko E
(2021)
Genomic diversity of Escherichia coli from healthy children in rural Gambia.
in PeerJ
Foster-Nyarko E
(2020)
Genomic diversity of Escherichia coli isolates from healthy children in rural Gambia
Gilroy R
(2020)
A Genomic Blueprint of the Chicken Gut Microbiome
Gilroy R
(2022)
Metagenomic investigation of the equine faecal microbiome reveals extensive taxonomic diversity.
in PeerJ
Glendinning L
(2019)
Assembly of hundreds of novel bacterial genomes from the chicken caecum
Glendinning L
(2021)
Author Correction: Assembly of hundreds of novel bacterial genomes from the chicken caecum.
in Genome biology
Hildebrand F
(2020)
Towards standardisation of naming novel prokaryotic taxa in the age of high-throughput microbiology.
in Gut
Konings F
(2021)
SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse.
in Nature microbiology
Pallen M
(2021)
Bacterial Nomenclature in the Era of Genomics
Pallen MJ
(2022)
Naming the unnamed: over 65,000 Candidatus names for unnamed Archaea and Bacteria in the Genome Taxonomy Database.
in International journal of systematic and evolutionary microbiology
Pallen MJ
(2021)
The status Candidatus for uncultured taxa of Bacteria and Archaea: SWOT analysis.
in International journal of systematic and evolutionary microbiology
Pallen MJ
(2021)
Bacterial nomenclature in the era of genomics.
in New microbes and new infections
Ravi A
(2019)
Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients.
in Microbial genomics
Ravi A
(2019)
Metagenomic profiling of ticks: Identification of novel rickettsial genomes and detection of tick-borne canine parvovirus.
in PLoS neglected tropical diseases
Thomson NM
(2022)
Remarkable genomic diversity among Escherichia isolates recovered from healthy chickens.
in PeerJ
Thomson NM
(2018)
Bacterial Flagellins: Does Size Matter?
in Trends in microbiology
Thomson NM
(2020)
Restoration of wild-type motility to flagellin-knockout Escherichia coli by varying promoter, copy number and induction strength in plasmid-based expression of flagellin.
in Current research in biotechnology
Thomson NM
(2018)
Giant flagellins form thick flagellar filaments in two species of marine ?-proteobacteria.
in PloS one