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Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host


Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts1. Host adaptation can potentially progress to host restriction, where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin-12 β1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harboured a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.

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Figure 1: Phylogeny of S. Enteritidis gastroenteritis isolates and blood isolates from the IL-12 β1 receptor-deficient patient.
Figure 2: Patient isolates have acquired a large number of pseudogenes.
Figure 3: Colonization of the murine host and interaction with epithelial-like cells by patient isolates.


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The authors thank D. Harris, G. Langridge and the Pathogen Informatics team for help with sequencing and bioinformatics and the Sanger Institute Research Support Facility for help with the animal studies. This work was funded by the Wellcome Trust through core funding for the Sanger Institute Pathogen Variation Group.

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Authors and Affiliations



R.A.K. and G.D. designed the study. E.J.K., D.K., R.D., A.C., A.M.L.L., J.H., R.A.K., E.G.K., J.H., J.F., S.C., L.K., S.K., D.G., T.W., C.H. and F.J.C. collected the data. E.J.K., R.A.K., T.D.O., J.F., J.P., S.H. and C.M. analysed the data. E.J.K., R.A.K., G.D., E.G.K. and J.P. wrote the manuscript.

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Correspondence to Robert A. Kingsley.

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The authors declare no competing financial interests.

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Supplementary Figures 1–10, Tables I–V, Discussion and References (PDF 3741 kb)

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Klemm, E., Gkrania-Klotsas, E., Hadfield, J. et al. Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host. Nat Microbiol 1, 15023 (2016).

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