Biology subjects

Grisard, E. C.

Publications and source records attributed to Grisard, E. C..

4 recordsLinked to original sources

bioRxiv2026

Comprehensive genomic analysis of Trypanosoma rangeli reveals key insights into the biology and evolution of this non-virulent American mammalian trypanosome

BackgroundTrypanosoma rangeli is a non-virulent hemoflagellate protozoan parasite that infects mammals, including humans, in Central and South America. It is primarily transmitted through the bites of triatomine bugs and shares an overlapping geographical distribution with T. cruzi, as well as triatomine vectors and mammalian hosts, and various shared surface antigens. The life cycle of T. rangeli differs from those of other human-infecting trypanosomes, such as T. cruzi and T. brucei, and the molecular mechanisms underlying host-parasite and host-vector interactions are not well understood, demanding improved molecular and genomic resources. ResultsThe use of a hybrid approach to sequence and assemble the T. rangeli genome, complemented by transcriptomics and proteomics for functional gene annotation, led to the generation of the near-complete genome sequence of the parasite. Detailed intra- and inter-specific comparative genomics allowed analysis of polymorphisms, genome structure and improved resolution of genes coding for important surface molecules such as Mucins, TASV and GP63. ConclusionsThe improved T. rangeli genome assembly, combined with comparative genomics has yielded novel biological insights. These included the first description of a metalloprotease activity, attributed to specific GP63 genes that are absent in Leishmania species. In addition, a TASV gene family that is absent in T. cruzi was identified, which indicates a possible role in the T. rangeli infection process.

microbiology↗

bioRxiv2021

Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure.

Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was progressive, gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.

microbiology↗

bioRxiv2018

Multidrug-resistant Gram-negative bacteria from patients, hospital environment and healthcare workers: a six-month cross-sectional study

Healthcare-associated infections (HAI) are an important public health threat with the multidrug-resistant (MDR) gram-negative bacteria (GNB) being of particular concern. Here we present the antimicrobial resistance profile of HAI-related GNB (HAIrB) isolated from patients (PT), healthcare workers (HCW) and hospital environment (HE) in a six-month screening program. From the 180 sampling points distributed in six hospital units, a total of 1,080 swabs were collected allowing the isolation of 390 HAIrB: 50.5% from HE, 42.6% from PT and 6.9% from HCW. Among the HAIrB, 32.6% were characterized as MDR and 38.7% as extended-spectrum cephalosporins resistant (ESC-R), showing no differences in the distribution between PT, HE and HCW. Carbapenem resistance (CARB-R) was detected for 17.7% of all HAIrB, being higher among Acinetobacter spp. isolates (36.5%), followed by Enterobacteriaceae (14.5%) and Pseudomonas spp. (11.8%). Except for the ICU, that revealed higher MDR, CARB-R and ESC-R rates, HAIrB-resistant profiles were similarly detected within the hospital units. Prevalence of blaKPC-like and blaCTX-M-1 {beta}-lactamases-resistance genes was higher in K. pneumoniae and E. cloacae complex, while blaOXA-23-like and blaSPM-like were higher in A. baumannii and P. aeruginosa, respectively. This study reveals that the spreading of HAIrB within a hospital environment is higher than predicted, indicating that healthcare workers, hospital areas and equipment are key players on dissemination of MDR gram-negative bacteria and shows that an active surveillance program can provide precise understanding and direct actions towards control of HAI.

microbiology↗

bioRxiv2018

Repeat-driven generation of antigenic diversity in a major human pathogen, Trypanosoma cruzi

Trypanosoma cruzi, a zoonotic kinetoplastid protozoan with a complex genome, is the causative agent of American trypanosomiasis (Chagas disease). The parasite uses a highly diverse repertoire of surface molecules, with roles in cell invasion, immune evasion and pathogenesis. Thus far, the genomic regions containing these genes have been impossible to resolve and it has been impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here present an improved genome assembly of a T. cruzi clade I (TcI) strain using high coverage PacBio single molecule sequencing, together with Illumina sequencing of 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene structure reveals an unusual duality in the organisation of the parasite genome, a core genomic region syntenous with related protozoa flanked by unique and highly plastic subtelomeric regions encoding surface antigens. The presence of abundant interspersed retrotransposons in the subtelomeres suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response. The comparative genomic analysis of the cohort of TcI strains revealed multiple cases of such recombination events involving surface molecule genes and has provided new insights into T. cruzi population structure.

genomics↗