Inferring bacterial transmission dynamics using deep sequencing genomic surveillance data
Identifying and interrupting transmission chains is important for controlling infectious diseases. One way to identify transmission pairs – two hosts in which infection was transmitted from one to the other – is using the variation of the pathogen within each single host (within-host variation). However, the role of such variation in transmission is understudied due to a lack of experimental and clinical datasets that capture pathogen diversity in both donor and recipient hosts. In this work, we assess the utility of deep-sequenced genomic surveillance (where genomic regions are sequenced hundreds to thousands of times) using a mouse transmission model involving controlled spread of the pathogenic bac- terium Citrobacter rodentium from infected to naïve female animals. We observe that within-host single nucleotide variants (iSNVs) are maintained over multiple transmission steps and present a model for inferring the likelihood that a given pair of sequenced samples are linked by transmission. In this work we show that, beyond the presence and absence of within-host variants, differences arising in the relative abundance of iSNVs (allelic frequency) can infer transmission pairs more precisely. Our approach further highlights the critical role bottlenecks play in reserving the within-host diversity during transmission.
Funding
National Institute of Health (R01AI128344)
University of Auckland’s Faculty of Medical and Health Sciences (9802- 3701152)
Maurice Wilkins Centre for Molecular Biodiscovery (9431-48516)
History
School affiliated with
- Department of Life Sciences (Research Outputs)
Publication Title
Nature CommunicationsVolume
14Pages/Article Number
6397Publisher
Nature ResearchExternal DOI
eISSN
2041-1723Date Submitted
2022-11-13Date Accepted
2023-09-27Date of First Publication
2023-10-31Date of Final Publication
2023-10-31Open Access Status
- Open Access