Biomedical subjects

Thierry Wirth

Publications and source records attributed to Thierry Wirth.

11 recordsLinked to original sources

PubMed2006

Sex and virulence in Escherichia coli: an evolutionary perspective.

Pathogenic Escherichia coli cause over 160 million cases of dysentery and one million deaths per year, whereas non-pathogenic E. coli constitute part of the normal intestinal flora of healthy mammals and birds. The evolutionary pathways underlying this dichotomy in bacterial lifestyle were investigated by multilocus sequence typing of a global collection of isolates. Specific pathogen types [enterohaemorrhagic E. coli, enteropathogenic E. coli, enteroinvasive E. coli, K1 and Shigella] have arisen independently and repeatedly in several lineages, whereas other lineages contain only few pathogens. Rates of evolution have accelerated in pathogenic lineages, culminating in highly virulent organisms whose genomic contents are altered frequently by increased rates of homologous recombination; thus, the evolution of virulence is linked to bacterial sex. This long-term pattern of evolution was observed in genes distributed throughout the genome, and thereby is the likely result of episodic selection for strains that can escape the host immune response.

Alleles↗

PubMed2005

Microsatellite analysis reveals genetic structure of Leishmania tropica.

The current rapid spread of leishmaniases caused by Leishmania tropica and the complexity of its clinical spectrum call for this parasite's epidemiological and evolutionary investigation. Evaluation of its population structure by isoenzyme electrophoresis and previous molecular biological analysis has proved difficult. In this study, we used 21 microsatellite loci to type 117 strains from different African and Asian locations. Eighty-one different genotypes were found. A genetic bottleneck supported by a gradient in the number of alleles and consistent with the geographical structure of the Middle East suggests an African origin of this species. A Bayesian approach identified 10 genetic clusters that correlated predominantly with geographical origin. The strains in the 'Asia' cluster form a very heterogeneous sub-population, with a varied but inter-related genotype that is geographically very widely dispersed and consistent with anthroponotic transmission of the parasite. The other nine clusters were more homogenous. The propagation of L. tropica appears to be predominantly clonal. In Africa and the Middle East, anthroponotic and zoonotic systems of distribution may contribute to the development of overlapping, genetically distinct populations of L. tropica.

Africa↗

PubMed2005

Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders.

Mutations in the leucine-rich, glioma-inactivated 1 gene, LGI1, cause autosomal-dominant lateral temporal lobe epilepsy via unknown mechanisms. LGI1 belongs to a subfamily of leucine-rich repeat genes comprising four members (LGI1-LGI4) in mammals. In this study, both comparative developmental as well as molecular evolutionary methods were applied to investigate the evolution of the LGI gene family and, subsequently, of the functional importance of its different gene members. Our phylogenetic studies suggest that LGI genes evolved early in the vertebrate lineage. Genetic and expression analyses of all five zebrafish lgi genes revealed duplications of lgi1 and lgi2, each resulting in two paralogous gene copies with mostly nonoverlapping expression patterns. Furthermore, all vertebrate LGI1 orthologs experience high levels of purifying selection that argue for an essential role of this gene in neural development or function. The approach of combining expression and selection data used here exemplarily demonstrates that in poorly characterized gene families a framework of evolutionary and expression analyses can identify those genes that are functionally most important and are therefore prime candidates for human disorders.

Animals↗

PubMed2005

Population genetics of microbial pathogens estimated from multilocus sequence typing (MLST) data.

The inference of population recombination (rho), population mutation (Theta), and adaptive selection is of great interest in microbial population genetics. These parameters can be efficiently estimated using explicit statistical frameworks (evolutionary models) that describe their effect on gene sequences. Within this framework, we estimated rho and Theta using a coalescent approach, and adaptive (or destabilizing) selection under heterogeneous codon-based and amino acid property models in microbial sequences from MLST databases. We analyzed a total of 91 different housekeeping gene regions (loci) corresponding to one fungal and sixteen bacterial pathogens. Our results show that these three population parameters vary extensively across species and loci, but they do not seem to be correlated. For the most part, estimated recombination rates among species agree well with previous studies. Over all taxa, the rho/Theta ratio suggests that each factor contributes similarly to the emergence of variant alleles. Comparisons of Theta estimated under finite- and infinite-site models indicate that recurrent mutation (i.e., multiple mutations at some sites) can increase Theta by up to 39%. Significant evidence of molecular adaptation was detected in 28 loci from 13 pathogens. Three of these loci showed concordant patterns of adaptive selection in two to four different species.

Alleles↗

PubMed2005

Deciphering host migrations and origins by means of their microbes.

Mitochondrial DNA and microsatellite sequences are powerful genetic markers for inferring the genealogy and the population genetic structure of animals but they have only limited resolution for organisms that display low genetic variability due to recent strong bottlenecks. An alternative source of data for deciphering migrations and origins in genetically uniform hosts can be provided by some of their microbes, if their evolutionary history correlates closely with that of the host. In this review, we first discuss how a variety of viruses, and the bacterium Helicobacter pylori, can be used as genetic tracers for one of the most intensively studied species, Homo sapiens. Then, we review statistical problems and limitations that affect the calculation of particular population genetic parameters for these microbes, such as mutation rates, with particular emphasis on the effects of recombination, selection and mode of transmission. Finally, we extend the discussion to other host-parasite systems and advocate the adoption of an integrative approach to both sampling and analysis.

Emigration and Immigration↗

PubMed2004

Microevolution and history of the plague bacillus, Yersinia pestis.

The association of historical plague pandemics with Yersinia pestis remains controversial, partly because the evolutionary history of this largely monomorphic bacterium was unknown. The microevolution of Y. pestis was therefore investigated by three different multilocus molecular methods, targeting genomewide synonymous SNPs, variation in number of tandem repeats, and insertion of IS100 insertion elements. Eight populations were recognized by the three methods, and we propose an evolutionary tree for these populations, rooted on Yersinia pseudotuberculosis. The tree invokes microevolution over millennia, during which enzootic pestoides isolates evolved. This initial phase was followed by a binary split 6,500 years ago, which led to populations that are more frequently associated with human disease. These populations do not correspond directly to classical biovars that are based on phenotypic properties. Thus, we recommend that henceforth groupings should be based on molecular signatures. The age of Y. pestis inferred here is compatible with the dates of historical pandemic plague. However, it is premature to infer an association between any modern molecular grouping and a particular pandemic wave that occurred before the 20th century.

Animals↗

PubMed2004

Distinguishing human ethnic groups by means of sequences from Helicobacter pylori: lessons from Ladakh.

The history of mankind remains one of the most challenging fields of study. However, the emergence of anatomically modern humans has been so recent that only a few genetically informative polymorphisms have accumulated. Here, we show that DNA sequences from Helicobacter pylori, a bacterium that colonizes the stomachs of most humans and is usually transmitted within families, can distinguish between closely related human populations and are superior in this respect to classical human genetic markers. H. pylori from Buddhists and Muslims, the two major ethnic communities in Ladakh (India), differ in their population-genetic structure. Moreover, the prokaryotic diversity is consistent with the Buddhists having arisen from an introgression of Tibetan speakers into an ancient Ladakhi population. H. pylori from Muslims contain a much stronger ancestral Ladakhi component, except for several isolates with an Indo-European signature, probably reflecting genetic flux from the Near East. These signatures in H. pylori sequences are congruent with the recent history of population movements in Ladakh, whereas similar signatures in human microsatellites or mtDNA were only marginally significant. H. pylori sequence analysis has the potential to become an important tool for unraveling short-term genetic changes in human populations.

DNA, Bacterial↗

PubMed2003

Decline of North Atlantic eels: a fatal synergy?

Panmictic species pose particular problems for conservation because their welfare can be addressed effectively only on a global scale. We recently documented by means of microsatellite analysis that the European eel (Anguilla anguilla) is not panmictic but instead shows genetic isolation by distance. In this study, we extended the analysis to the American eel (A. rostrata) by applying identical analytical procedures and statistical power. Results obtained for the American eel were in sharp contrast with those obtained for the European eel: the null hypothesis of panmixia could not be rejected, and no isolation by distance was detected. This implies that the species must be managed as a single population. Using Bayesian statistics, we also found that the effective population sizes for both species were surprisingly low and that the populations had undergone severe contractions, most probably during the Wisconsinan glaciation. The apparent sensitivity of eels to climatic changes affecting the strength and position of the Gulf Stream 20,000 years ago is particularly worrying, given the effects of the ongoing global warming on the North Atlantic climate. Moreover, additional short-term stresses such as surging glass eel prizes, overfishing and lethal parasitic infections negatively affect eel population size. The fascinating transatlantic migration and life cycle of Atlantic eels is also their Achilles' heel as these negative short- and long-term effects will probably culminate in a fatal synergy if drastic conservation measures are not implemented to protect these international biological resources.

Anguilla↗

PubMed2003

Traces of human migrations in Helicobacter pylori populations.

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.

Africa↗

PubMed2002

Prospective study of a serogroup X Neisseria meningitidis outbreak in northern Ghana.

After an epidemic of serogroup A meningococcal meningitis in northern Ghana, a gradual disappearance of the epidemic strain was observed in a series of five 6-month carriage surveys of 37 randomly selected households. As serogroup A Neisseria meningitidis carriage decreased, an epidemic of serogroup X meningococcal carriage occurred, which reached 18% (53/298) of the people sampled during the dry season of 2000, coinciding with an outbreak of serogroup X disease. These carriage patterns were unrelated to that of Neisseria lactamica. Multilocus sequence typing and pulsed-field gel electrophoresis of the serogroup X bacteria revealed strong similarity with other strains isolated in Africa during recent decades. Three closely related clusters with distinct patterns of spread were identified among the Ghanian isolates, and further microevolution occurred after they arrived in the district. The occurrence of serogroup X outbreaks argues for the inclusion of this serogroup into a multivalent conjugate vaccine against N. meningitidis.

Adolescent↗

PubMed2002

Clonal groupings in serogroup X Neisseria meningitidis.

The genetic diversity of 134 serogroup X Neisseria meningitis isolates from Africa, Europe, and North America was analyzed by multilocus sequence typing and pulsed-field gel electrophoresis. Although most European and American isolates were highly diverse, one clonal grouping was identified in sporadic disease and carrier strains isolated over the last 2 decades in the United Kingdom, the Netherlands, Germany, and the United States. In contrast to the diversity in the European and American isolates, most carrier and disease isolates recovered during the last 30 years in countries in the African meningitis belt belonged to a second clonal grouping. During the last decade, these bacteria have caused meningitis outbreaks in Niger and Ghana. These results support the development of a comprehensive conjugate vaccine that would include serogroup X polysaccharide.

Africa↗