# Complete genomes of Rickettsia typhi reveal a clonal population

## TL;DR

Rickettsia typhi, which causes murine typhus, has a highly stable genome with minimal genetic variation, aiding in diagnostic and vaccine development.

## Contribution

The study reveals the clonal nature of R. typhi through sequencing 25 new genomes, showing minimal genetic diversity and implications for diagnostics and vaccines.

## Key findings

- R. typhi genomes show extremely low nucleotide diversity (π = 1.27e-05) and evidence of purifying selection.
- Phylogenetic analysis reveals clustering by historic or modern origin, not host origin.
- The highly conserved genome suggests strong evolutionary constraints in this obligate intracellular parasite.

## Abstract

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 (π) 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.

Rickettsia typhi is the bacteria which causes murine typhus, an infectious disease transmitted by fleas. It is often underdiagnosed because its symptoms are similar to many other illnesses. To better understand this pathogen, we examined a large collection of R. typhi genomes taken from recent patient infections and historical bacterial collections covering almost a century. The findings showed that R. typhi has evolved very slowly over time. Even across nations, hosts, and decades, its genetic composition is extremely stable. This implies that the population of the bacteria is highly uniform and their genetics differ very little from one another. This low level of genetic variation will help in the design of effective R. typhi diagnostic tests, and simplify future vaccine development.