Project description:Here we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos regions using genome-scanning, a microarray-based technique which delineates the majority of single-base changes, indels and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon is highly structured with a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes indicating mutations arising during self-mating or mitotic replication. The data also reveal that 1 or 2 meioses separate different isolates showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pair-wise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase clindamycin EC50 in strains harboring one of these mutations. This evidence of clindamycin resistant parasites in the Amazon suggests a shift should be made in health policy away from quinine+clindamycin therapy for malaria in pregnant women and infants and that the development of new lincosamide antibiotics for malaria should be reconsidered.
Project description:Here we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos regions using genome-scanning, a microarray-based technique which delineates the majority of single-base changes, indels and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon is highly structured with a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes indicating mutations arising during self-mating or mitotic replication. The data also reveal that 1 or 2 meioses separate different isolates showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pair-wise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase clindamycin EC50 in strains harboring one of these mutations. This evidence of clindamycin resistant parasites in the Amazon suggests a shift should be made in health policy away from quinine+clindamycin therapy for malaria in pregnant women and infants and that the development of new lincosamide antibiotics for malaria should be reconsidered. Genome DNA from Peruvian Isolates vs. Reference 3D7
Project description:Vulvovaginal candidiasis (VVC) affects nearly ¾ of women during their lifetime and its symptoms seriously reduce quality of life. Although Candida albicans is a common commensal, it is unknown if VVC results from a commensal to pathogenic state switch, if only some strains can cause VVC, and/or if there is displacement of commensal strains with more pathogenic strains. We studied a set of VVC and Colonizing C. albicans strains to identify consistent in vitro phenotypes associated with one group or the other. We find that the strains do not differ in overall genetic profile or behavior in culture media (i.e. MLST profile, rate of growth, filamentation), but they show strikingly different behavior during their interactions with vaginal epithelial cells. Epithelial infections with VVC-derived strains yielded stronger fungal proliferation and shedding of fungi and epithelial cells. RNA-seq analysis of representative epithelial cell infections with selected pathogenic or commensal isolates identified several differentially activated epithelial signaling pathways, including the integrin, ferroptosis and type I interferon pathways; the latter has been implicated in damage protection. The type I interferon pathway is activated more by the Colonizing strains, while type I interferon inhibition selectively increases fungal shedding of only the colonizing fungi. These data suggest that VVC strains may intrinsically have more pathogenic potential via differential elicitation of epithelial responses, including type I interferon pathway. Therefore, it may be possible to evaluate pathogenic potential in vitro to refine VVC diagnosis.
2023-02-07 | GSE207081 | GEO
Project description:Arbuscular Mycorrhizal Fungi in organic layers of the Amazon region