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Phasome analysis of pathogenic and commensal Neisseria species expands the known repertoire of phase variable genes, and highlights common adaptive strategies

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posted on 2018-05-18, 14:24 authored by Joseph J. Wanford, Luke R. Green, Jack Aidley, Christopher D. Bayliss
Pathogenic Neisseria are responsible for significantly higher levels of morbidity and mortality than their commensal relatives despite having similar genetic contents. Neisseria possess a disparate arsenal of surface determinants that facilitate host colonisation and evasion of the immune response during persistent carriage. Adaptation to rapid changes in these hostile host environments is enabled by phase variation (PV) involving high frequency, stochastic switches in expression of surface determinants. In this study, we analysed 89 complete and 79 partial genomes, from the NCBI and Neisseria PubMLST databases, representative of multiple pathogenic and commensal species of Neisseria using PhasomeIt, a new program that identifies putatively phase-variable genes and homology groups by the presence of simple sequence repeats (SSR). We detected a repertoire of 884 putative PV loci with maxima of 54 and 47 per genome in gonococcal and meningococcal isolates, respectively. Most commensal species encoded a lower number of PV genes (between 5 and 30) except N. lactamica wherein the potential for PV (36–82 loci) was higher, implying that PV is an adaptive mechanism for persistence in this species. We also characterised the repeat types and numbers in both pathogenic and commensal species. Conservation of SSR-mediated PV was frequently observed in outer membrane proteins or modifiers of outer membrane determinants. Intermittent and weak selection for evolution of SSR-mediated PV was suggested by poor conservation of tracts with novel PV genes often occurring in only one isolate. Finally, we describe core phasomes—the conserved repertoires of phase-variable genes—for each species that identify overlapping but distinctive adaptive strategies for the pathogenic and commensal members of the Neisseria genus.

Funding

We are thankful for funding from the Medical Research Council (grant MR/M020193/1) awarded to Christopher Bayliss, the Biotechnology and Biological Sciences Research Council (grant BB1193044) for funding Jack Aidley. The authors would like to acknowledge the MRC IMPACT PhD studentship scheme for funding JW.

History

Citation

PLoS ONE, 2018, 13 (5), e0196675

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Genetics and Genome Biology

Published in

PLoS ONE

Publisher

Public Library of Science

Acceptance date

2018-04-17

Copyright date

2018

Available date

2018-05-18

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196675

Notes

The dataset can be accessed online at: https://figshare.com/s/d31b7b0b6ca4aeeb48df. The PhasomeIt program can also be downloaded online from: https://github.com/JackAidley/PhasomeIt/. All other relevant data are within the paper and its Supporting Information files.

Language

en

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