Biology subjects

Samuel K Sheppard

Publications and source records attributed to Samuel K Sheppard.

4 recordsLinked to original sources

bioRxiv2016

Genomic plasticity and rapid host switching promote the evolution of generalism in the zoonotic pathogen Campylobacter

Horizontal gene transfer accelerates bacterial adaptation to novel environments, allowing selection to act on genes that have evolved in multiple genetic backgrounds. This can lead to ecological specialization. However, little is known about how zoonotic bacteria maintain the ability to colonize multiple hosts whilst competing with specialists in the same niche. Here we develop a stochastic evolutionary model and show how genetic transfer of niche specifying genes and the opportunity for host transition can interact to promote the emergence of host generalist lineages of the zoonotic bacterium Campylobacter. Using a modelling approach we show that increasing levels of recombination enhance the efficiency with which selection can fix combinations of beneficial alleles, speeding adaptation. We then show how these predictions change in a multi-host system, with low levels of recombination, consistent with real r/m estimates, increasing the standing variation in the population, allowing a more effective response to changes in the selective landscape. Our analysis explains how observed gradients of host specialism and generalism can evolve in a multihost system through the transfer of ecologically important loci among coexisting strains.

Microbiology↗

bioRxiv2016

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found four outer membrane proteins with atypical levels of Asian ancestry in American strains, including the adhesion factor AlpB, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.\n\nAuthor SummaryHelicobacter pylori is one of the best studied examples of an intimate association between bacteria and humans, due to its ability to colonize the stomach for decades and to transmit from generation to generation. A number of studies have sought to link diversity in H. pylori to human migrations but there are some discordant signals such as an \"out of Africa\" dispersal within the last few thousand years that has left a much stronger signal in bacterial genomes than in human ones. In order to understand how such discrepancies arise, we have investigated the evolution of H. pylori during the recent colonization of the Americas. We find that bacterial populations evolve quickly and can spread rapidly to people of different ethnicities. Distinct new bacterial subpopulations have formed in Colombia from a European source and in Nicaragua and the US from African sources. Genetic exchange between bacterial populations is rampant within Central and South America but is uncommon within North America, which may reflect differences in prevalence. Our results also suggest that adaptation of bacteria to particular human ethnic groups may be confined to a handful of genes involved in interaction with the immune system.

Genetics↗

bioRxiv2016

Genetic and chemical differentiation of Campylobacter coli and Campylobacter jejuni lipooligosaccharide pathways

Despite the importance of lipooligosaccharides (LOS) in the pathogenicity of campylobacteriosis, little is known about the genetic and phenotypic diversity of LOS in C. coli. In this study, we investigated the distribution of LOS locus classes among a large collection of unrelated C. coli isolates sampled from several different host species. Furthermore, we paired C. coli genomic information and LOS chemical composition for the first time to identify mechanisms consistent with the generation of LOS phenotypic heterogeneity. After classifying three new LOS locus classes, only 85% of the 144 isolates tested were assigned to a class, suggesting higher genetic diversity than previously thought. This genetic diversity is at the basis of a completely unexplored LOS structure heterogeneity. Mass spectrometry analysis of the LOS of nine isolates, representing four different LOS classes, identified two features distinguishing C. coli LOS from C. jejunis. GlcN-GlcN disaccharides were present in the lipid A backbone in contrast to the GlcN3N-GlcN backbone observed in C. jejuni. Moreover, despite that many of the genes putatively involved in Qui3pNAcyl were absence in the genomes of various isolates, this rare sugar was found in the outer core of all C. coli. Therefore, regardless the high genetic diversity of LOS biosynthes is locus in C. coli, we identified species-specific phenotypic features of C. coli LOS which might explain differences between C. jejuni and C. coli in terms of population dynamics and host adaptation.\n\nDepositories (where applicable)The whole genome sequences of C. coli are publicly available on the RAST server (http://rast.nmpdr.org) with guest account (login and password guest) under IDs: 195.91, 195.96-195.119, 195.124-195.126, 195.128-195.130, 195.133, 195.134, 6666666.94320

Microbiology↗

bioRxiv2015

The impact of host metapopulation structure on the population genetics of colonizing bacteria

Many key bacterial pathogens are frequently carried asymptomatically, and the emergence and spread of these opportunistic pathogens can be driven, or mitigated, via demographic changes within the host population. These inter-host transmission dynamics combine with basic evolutionary parameters such as rates of mutation and recombination, population size and selection, to shape the genetic diversity within bacterial populations. Whilst many studies have focused on how molecular processes underpin bacterial population structure, the impact of host migration and the connectivity of the local populations has received far less attention. A stochastic neutral model incorporating heightened local transmission has been previously shown to fit closely with genetic data for several bacterial species. However, this model did not incorporate transmission limiting population stratification, nor the possibility of migration of strains between subpopulations, which we address here by presenting an extended model. The model captures the observed population patterns for the common nosocomial pathogens Staphylococcus epidermidis and Enterococcus faecalis, while Staphylococcus aureus and Enterococcus faecium display deviations attributable to adaptation. It is demonstrated analytically and numerically that expected strain relatedness may either increase or decrease as a function of increasing migration rate between subpopulations, being a complex function of the rate at which microepidemics occur in the metapopulation. Moreover, it is shown that in a structured population markedly different rates of evolution may lead to indistinguishable patterns of relatedness among bacterial strains; caution is thus required when drawing evolution inference in these cases.

Genetics↗