Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations

ABSTRACT Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a wides...

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Autores principales:	Jack Aidley, Shweta Rajopadhye, Nwanekka M. Akinyemi, Lea Lango-Scholey, Christopher D. Bayliss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1049e634d6cf4d498b5eccabfc0703f5
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spelling	oai:doaj.org-article:1049e634d6cf4d498b5eccabfc0703f52021-11-15T15:50:59ZNonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations10.1128/mBio.02311-162150-7511https://doaj.org/article/1049e634d6cf4d498b5eccabfc0703f52017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02311-16https://doaj.org/toc/2150-7511ABSTRACT Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using both in vitro testing of C. jejuni populations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental and in silico modeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes. IMPORTANCE Transmission and within-host spread of pathogenic organisms are associated with selective and nonselective bottlenecks that significantly reduced population diversity. In several bacterial pathogens, hypermutable mechanisms have evolved that mediate high-frequency reversible switching of specific phenotypes, such as surface structures, and hence counteract bottleneck-associated reductions in population diversity. Here, we investigated how combinations of hypermutable simple sequence repeats interact with nonselective bottlenecks by using a stochastic computer model and experimental data for Campylobacter jejuni, a food-borne pathogen. We find that bottleneck size qualitatively alters the output populations, with large bottlenecks maintaining population diversity while small bottlenecks produce dramatic shifts in the prevalence of particular variants. We conclude that narrow bottlenecks are capable of producing host-to-host variation in repeat-controlled bacterial phenotypes, leading to a potential for stochastic person-to-person variations in disease outcome for C. jejuni and other organisms with similar hypermutable mechanisms.Jack AidleyShweta RajopadhyeNwanekka M. AkinyemiLea Lango-ScholeyChristopher D. BaylissAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jack Aidley Shweta Rajopadhye Nwanekka M. Akinyemi Lea Lango-Scholey Christopher D. Bayliss Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations
description	ABSTRACT Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using both in vitro testing of C. jejuni populations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental and in silico modeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes. IMPORTANCE Transmission and within-host spread of pathogenic organisms are associated with selective and nonselective bottlenecks that significantly reduced population diversity. In several bacterial pathogens, hypermutable mechanisms have evolved that mediate high-frequency reversible switching of specific phenotypes, such as surface structures, and hence counteract bottleneck-associated reductions in population diversity. Here, we investigated how combinations of hypermutable simple sequence repeats interact with nonselective bottlenecks by using a stochastic computer model and experimental data for Campylobacter jejuni, a food-borne pathogen. We find that bottleneck size qualitatively alters the output populations, with large bottlenecks maintaining population diversity while small bottlenecks produce dramatic shifts in the prevalence of particular variants. We conclude that narrow bottlenecks are capable of producing host-to-host variation in repeat-controlled bacterial phenotypes, leading to a potential for stochastic person-to-person variations in disease outcome for C. jejuni and other organisms with similar hypermutable mechanisms.
format	article
author	Jack Aidley Shweta Rajopadhye Nwanekka M. Akinyemi Lea Lango-Scholey Christopher D. Bayliss
author_facet	Jack Aidley Shweta Rajopadhye Nwanekka M. Akinyemi Lea Lango-Scholey Christopher D. Bayliss
author_sort	Jack Aidley
title	Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations
title_short	Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations
title_full	Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations
title_fullStr	Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations
title_full_unstemmed	Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations
title_sort	nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/1049e634d6cf4d498b5eccabfc0703f5
work_keys_str_mv	AT jackaidley nonselectivebottleneckscontrolthedivergenceanddiversificationofphasevariablebacterialpopulations AT shwetarajopadhye nonselectivebottleneckscontrolthedivergenceanddiversificationofphasevariablebacterialpopulations AT nwanekkamakinyemi nonselectivebottleneckscontrolthedivergenceanddiversificationofphasevariablebacterialpopulations AT lealangoscholey nonselectivebottleneckscontrolthedivergenceanddiversificationofphasevariablebacterialpopulations AT christopherdbayliss nonselectivebottleneckscontrolthedivergenceanddiversificationofphasevariablebacterialpopulations
_version_	1718427381813739520

Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations

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