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Michel Tibayrenc

Publications and source records attributed to Michel Tibayrenc.

30 records · Page 2Linked to original sources
PubMed2003

Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area.

Deciphering the structure of pathogen populations is instrumental for the understanding of the epidemiology and history of infectious diseases and for their control. Although Mycobacterium tuberculosis is the most widespread infectious agent in humans, its actual population structure has remained hypothetical until now because: (i) its structural genes are poorly polymorphic; (ii) adequate samples and appropriate statistics for population genetic analysis have not been considered. To investigate this structure, we analysed the statistical associations (linkage disequilibrium) between 12 independent M. tuberculosis minisatellite-like loci by high-throughput genotyping within a model population of 209 isolates representative of the genetic diversity in an area with a very high incidence of tuberculosis. These loci contain variable number tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed repetitive units (MIRUs). Highly significant linkage disequilibrium was detected among the MIRU-VNTR loci in this model. This linkage disequilibrium was also evident when the MIRU-VNTR types were compared with the IS6110 restriction fragment length polymorphism types. These results support a predominant clonal evolution of M. tuberculosis.

Bacterial Typing Techniques↗
PubMed2003

Chemotherapy with benznidazole and itraconazole for mice infected with different Trypanosoma cruzi clonal genotypes.

The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.

Animals↗
PubMed2002

Microsatellite analysis of Toxoplasma gondii shows considerable polymorphism structured into two main clonal groups.

Previous studies on Toxoplasma gondii population structure, based essentially on multilocus restriction fragment length polymorphism analysis or on multilocus enzyme electrophoresis, indicated that T. gondii comprises three clonal lineages. These studies showed a weak polymorphism of the markers (2-4 alleles by locus). In this study, we used eight microsatellite markers to type 84 independent isolates from humans and animals. Two microsatellite markers were present in the introns of two genes, one coding for beta-tubulin and the other for myosin A, and six were found in expressed sequence tags. With 3-16 alleles detected, these markers can be considered as the most discriminating multilocus single-copy markers available for typing T. gondii isolates. This high discriminatory power of microsatellites made it possible to detect mixed infections and epidemiologically related isolates. Evolutionary genetic analyses of diversity show that the T. gondii population structure consists of only two clonal lineages that can be equated to discrete typing units, but there is some evidence of occasional genetic exchange that could explain why one of these discrete typing units is less clearly individualised than the other.

Animals↗
PubMed2002

Evolutionary genetics and molecular diagnosis of Leishmania species.

An extensive study has been performed on various natural populations of Leishmania from the 'Old' and 'New Worlds' using multilocus enzyme electrophoresis and random amplification of polymorphic deoxyribonucleic acid. The data are interpreted in evolutionary genetic terms in order to give a firm basis to studies dealing with the relevant medical properties of pathogens. We confirm that Leishmania undergoes clonal evolution with occasional phenomena of hybridization. This suggests that the microorganism genotypes are stable in space and time and consequently have epidemiological and medical relevance. It is crucial to have a clear definition of the taxa to be identified. In the case of Leishmania, there is at present no firm consensus on the species concept. We propose that any new species of Leishmania should correspond to a 'discrete typing unit' that exhibits specific medical and/or epidemiological characters. Based on this approach, the species status of L. peruviana can be supported. On the contrary, L. panamensis cannot be clearly distinguished from L. guyanensis. Our studies on the genetic diversity of Leishmania show that a given stock is not representative of the genus, the subgenera, or any species. We suggest that the genetic polymorphism of Leishmania has a strong impact on the parasite's biomedical properties.

Animals↗
PubMed2002

The clonal theory of parasitic protozoa: 12 years on.

The question of population structure in parasitic protozoa has recently gained a renewed topicality with significant contributions on medically important pathogens, such as Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium parvum. The proposals that initiated this debate are reviewed here and the subsequent developments of the clonal theory, in light of recent contributions, are examined.

Animals↗
PubMedDate not supplied

Lack of correlation between in vitro susceptibility to Benznidazole and phylogenetic diversity of Trypanosoma cruzi, the agent of Chagas disease.

Chagas disease remains an important health problem in Central and South America. Nitroimidazole derivative drugs like Benznidazole are commonly used to treat Trypanosoma cruzi infection. Natural variation of drug susceptibility between various T. cruzi stocks has been proposed as a possible explanation of treatment failure. Thus, the aim of this work was to determine potential correlations between in vitro Benznidazole susceptibility of different T. cruzi stocks and their genetic diversity. For this purpose, 16 natural stocks representing the overall genetic diversity of the parasite were analysed. Genetic characterisation was assessed by both random amplified polymorphic DNA (RAPD) and multilocus enzyme electrophoresis (MLEE) analyses. Drug activity was determined by two complementary methods, the MTT-PMS micro-method and FACs analysis. The 50% inhibitory concentrations (IC(50)s) were determined. Important variation of IC(50) values (7.3-16.9 microM) among stocks belonging to different discrete typing units (DTUs) was recorded. Further, correlation analysis showed that natural susceptibility to Benznidazole in T. cruzi expressed as IC(50) level was not related with its genetic structure represented by the different DTUs. These results are discussed in relation with the proposed hypothesis establishing a link between genetic diversity and biological behaviour in T. cruzi.

Analysis of Variance↗