July 7, 2019  |  

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

Authors: Klemm, Elizabeth J and Gkrania-Klotsas, Effrossyni and Hadfield, James and Forbester, Jessica L and Harris, Simon R and Hale, Christine and Heath, Jennifer N and Wileman, Thomas and Clare, Simon and Kane, Leanne and Goulding, David and Otto, Thomas D and Kay, Sally and Doffinger, Rainer and Cooke, Fiona J and Carmichael, Andrew and Lever, Andrew Ml and Parkhill, Julian and MacLennan, Calman A and Kumararatne, Dinakantha and Dougan, Gordon and Kingsley, Robert A

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 hosts(1). 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 (IL)-12 ß-1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harbored 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.

Journal: Nature microbiology
DOI: 10.1038/NMICROBIOL.2015.23
Year: 2016

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