Biology subjects

Robinson, M. T.

Publications and source records attributed to Robinson, M. T..

2 recordsLinked to original sources

bioRxiv2025

Complete genomes of Rickettsia typhi reveal a clonal population

Murine typhus, caused by infection with Rickettsia typhi, is a neglected disease contributing to infectious disease burden in south- and southeast Asia. Despite its importance, we have minimal knowledge of the genomics of R. typhi, with only four complete genomes being sequenced prior to this work. We sequenced a further 25 genomes including historical strains collected before 1976 from both human and rat hosts, and recent genomes isolated from patients at a single hospital in Laos. Whole genome SNP analysis reveals extremely low levels of genetic diversity across the 29 genomes, with overall nucleotide diversity ({pi}) of 1.27e-05 and evidence of purifying selection, and a minimal pan-genome. Phylogenetic analysis shows clustering of the genome by historic or modern origin, with the exception of one modern strain which is most closely related to historic strains from Thailand, and no clustering by host origin. The highly conserved genome of R. typhi suggests strong constraints on genome evolution in this obligate intracellular parasite, and has implications for the design of future murine typhus diagnostic tools and vaccines. Impact StatementRickettsia typhi is the causative agent of murine typhus, an infectious disease that causes morbidity and mortality in humans. This study has expanded the genomic dataset from a small number of genomes to a comprehensive collection of 29 complete genomes. The genome comparison includes historic and modern strains and reveals a clonal population structure with minimal genetic diversity across time. This shows the evolutionary stability of R. typhi, which is most likely due to strong purifying selection and an intracellular lifestyle. This extremely low genomic variation has significant impacts for the development of murine typhus vaccines and robust diagnostic assays.

microbiology↗

bioRxiv2018

MinION sequencing enables rapid whole genome assembly of Rickettsia typhi in a resource-limited setting

The infrastructure challenges and costs of next-generation sequencing have been largely overcome, for many sequencing applications, by Oxford Nanopore Technologies portable MinION sequencer. However the question remains open whether MinION-based bacterial whole-genome sequencing (WGS) is by itself sufficient for the accurate assessment of phylogenetic and epidemiological relationships between isolates and whether such tasks can be undertaken in resource-limited settings. To investigate this question, we sequenced the genome of an isolate of Rickettsia typhi, an important and neglected cause of fever across much of the tropics and subtropics, for which only three genomic sequences previously existed. We prepared and sequenced libraries on a MinION in Vientiane, Lao PDR using v9.5 chemistry and in parallel we sequenced the same isolate on the Illumina platform in a genomics laboratory in the UK. The MinION sequence reads yielded a single contiguous assembly, in which the addition of Illumina data revealed 226 base-substitution and 5,856 in/del errors. The combined assembly represents the first complete genome sequence of a human R. typhi isolate collected in the last 50 years and differed from the genomes of existing strains collected over a 90-year time period at very few sites, and with no re-arrangements. Filtering based on the known error profile of MinION data improved the accuracy of the Nanopore-only assembly. However, the frequency of false-positive errors remained greater than true sequence divergence from recorded sequences. While Nanopore-only sequencing cannot yet recover phylogenetic signal in R. typhi, such an approach may be applicable for more diverse organisms.

genomics↗