Journal Article

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

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

2016

Overview

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-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.

• Subject: Adaptation, Biological / Bacteremia - microbiology / Evolution, Molecular / Gene Deletion / Genetic Variation / Genome, Bacterial / Host-Pathogen Interactions / Humans / Immunocompromised Host / Mutation Rate / MutS DNA Mismatch-Binding Protein - deficiency / Phylogeny / Salmonella enteritidis - classification / Salmonella enteritidis - genetics / Salmonella enteritidis - isolation & purification / Salmonella Infections - microbiology / Time Factors