Phase III Clinical Trial to Evaluate Ivermectin in the Reduction of Mansonella ozzardi infection in the Brazilian Amazon

et al. 2023

Preprint

The filarial parasitesMansonella ozzardiandMansonella perstans, causative agents of mansonellosis, infect hundreds of millions of people worldwide, yet remain among the most understudied of the human filarial pathogens.M. ozzardiis highly prevalent in Latin American countries and Caribbean Islands, whileM. perstansis predominantly found in sub-Saharan Africa as well in a few areas in South America. In addition to the differences in their geographical distribution, the two parasites are transmitted by different insect vectors, as well as exhibit differences in their responses to commonly used anthelminthic drugs. The lack of genome information has hindered investigations into the biology and evolution of Mansonella parasites and understanding the molecular basis of the clinical differences between species. In the current study, high quality genomes of two independent clinical isolates ofM. perstansfrom Cameroon and twoM. ozzardiisolates one from Brazil and one from Venezuela are reported. The genomes are approximately 76 Mb in size, encode about 10,000 genes each, and are largely complete based on BUSCO scores of about 90%, similar to other completed filarial genomes. These sequences represent the first genomes from Mansonella parasites and enabled a comparative genomic analysis of the similarities and differences between Mansonella and other filarial parasites. Horizontal DNA transfers (HDT) from mitochondria (nuMTs) as well as transfers from genomes of endosymbiotic Wolbachia bacteria (nuWTs) to the host nuclear genome were identified and analyzed. Sequence comparisons and phylogenetic analysis of known targets of anti-filarial drugs diethylcarbamazine (DEC), ivermectin and mebendazole revealed thatM. ozzardilacks an ortholog ofgon-2, a target for DEC, whileM. perstanslacks an ortholog ofavr-14, a target of ivermectin. These new reference genome sequences will provide a valuable resource for further studies on biology, symbiosis, evolution and drug discovery.

Section: Resultsmentioning

confidence: 99%

Section: Analysis and Comparison Of Genes Encoding Drug Targets For T...mentioning

confidence: 99%

Genomes of the human filarial parasitesMansonella perstansandMansonella ozzardi

et al. 2023

Preprint

“…Written informed consent was obtained from all patients or their parents or guardians if participants were minors aged <18 years. Diagnosed infections were treated with a single dose of 0.2 mg/kg of ivermectin after blood sampling ( De Almeida Basano et al 2018 ; Lima et al 2018 , 39).…”

Section: Methodsmentioning

confidence: 99%

Multiple Lineages of Nematode-Wolbachia Symbiosis in Supergroup F and Convergent Loss of Bacterioferritin in Filarial Wolbachia

Genome Biology and Evolution

et al. 2023

The intracellular endosymbiotic proteobacteria Wolbachia have evolved across the phyla nematoda and arthropoda. In Wolbachia phylogeny, supergroup F is the only clade known so far with members from both arthropod and filarial nematode hosts and therefore can provide unique insights into their evolution and biology. In this study, 4 new supergroup F Wolbachia genomes have been assembled using a metagenomic assembly and binning approach, wMoz and wMpe from the human filarial parasites Mansonella ozzardi and Mansonella perstans, and wOcae and wMoviF from the blue mason bee Osmia caerulescens and the sheep ked Melophagus ovinus respectively. A comprehensive phylogenomic analysis revealed two distinct lineages of filarial Wolbachia in supergroup F, indicating multiple horizontal transfer events between arthropod and nematode hosts. The analysis also reveals that the evolution of Wolbachia-filaria symbioses is accompanied by a convergent pseudogenization and loss of the bacterioferritin gene, a phenomenon found to be shared by all filarial Wolbachia, even those outside supergroup F. These observations indicate that differences in heme metabolism might be a key feature distinguishing filarial and arthropod Wolbachia. The new genomes provide a valuable resource for further studies on symbiosis, evolution, and the discovery of new antibiotics to treat mansonellosis.

“…Written informed consent was obtained from all patients, or their parents or guardians if participants were minors aged <18 years. Diagnosed infections were treated with a single dose of 0.2 mg/kg of ivermectin after blood sampling (Basano et al 2018; Lima et al 2018, 39).…”

Section: Methodsmentioning

confidence: 99%

Multiple origins of nematode-Wolbachiasymbiosis in supergroup F and convergent loss of bacterioferritin in filarialWolbachia

et al. 2021

Preprint

Mansonella ozzardi and Mansonella perstans, filarial parasites infecting millions of people worldwide, harbor their unique obligate endosymbionts, the alpha-proteobacteria Wolbachia wMoz and wMpe, respectively. Currently, little is known about these Wolbachia and no genome sequences are available. In the current study, high quality draft genomes of wMoz and wMpe were assembled from complex clinical samples using a metagenome assembly and binning approach. These represent the first genomes from supergroup F Wolbachia originating from human parasites and share features characteristic of filarial as well arthropod Wolbachia, consistent with their position in supergroup F. Metagenomic data analysis was also used to estimate Wolbachia titers, which revealed wide variation in levels across different clinical isolates, addressing the contradicting reports on presence or absence of Wolbachia in M. perstans. These findings may have implications for the use antibiotics to treat mansonellosis. The wMoz and wMpe genome sequences provide a valuable resource for further studies on symbiosis, evolution and drug discovery.