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Biology subjects

Caldeira, R. L.

Publications and source records attributed to Caldeira, R. L..

2 recordsLinked to original sources

Environmental RNA improves detection and surveillance of schistosomiasis transmission

Environmental diagnosis of schistosomiasis, a tropical disease affecting more than 250 million people globally, is still challenging, which limits efficient eradication plans. There is a crucial need for resolutive and highly sensitive environmental tools to improve disease control. However, a major obstacle is the inability of current methods, including environmental DNA (eDNA), to distinguish infectious parasite life stages. Here, we develop and validate an environmental RNA (eRNA) approach that enables the detection and absolute quantification of Schistosoma mansoni miracidia and cercariae directly from water samples. After identifying life stage-specific transcripts, we design specific ddPCR assays which are strongly specific to S. mansoni and to each life stage. Comparing with eDNA assays, laboratory experiments demonstrate that stage-specific eRNA assays accurately reflect the relative abundance of each life stage, detect nucleic acids released from organisms, exhibit detection limits tenfold lower than eDNA assays. Also, under laboratory conditions, RNA persists in water longer than DNA. Field validation at six endemic sites in Brazil confirms that eRNA outperforms eDNA and conventional snail surveys in detecting active presence of S. mansoni cercariae, which indicates schistosomiasis transmission risk to humans locally. By enabling active-stage discrimination in environmental monitoring and improving sensitivity (compared to eDNA), our study advances both fundamental understanding and applied surveillance of schistosomiasis transmission, supporting elimination initiatives in affected regions.

ecology↗

Diminished adherence of snail hemocytes to schistosome sporocysts of Schistosoma mansoni following programmed knockout of the allograft inflammatory factor of Biomphalaria glabrata

BackgroundLarval development in an intermediate host gastropod snail of the genus Biomphalaria is an obligatory component of the life cycle of Schistosoma mansoni. Understanding of the mechanism(s) of host defense may hasten the development of tools that block transmission of schistosomiasis. The allograft inflammatory factor 1, AIF, which is evolutionarily conserved and expressed in phagocytes, is a marker of macrophage activation in both mammals and invertebrates. AIF enhances cell proliferation and migration. The embryonic cell line, termed Bge, from Biomphalaria glabrata is a versatile resource for investigation of the snail-schistosome relationship since Bge exhibits a hemocyte-like phenotype. Hemocytes perform central roles in innate and cellular immunity in gastropods and in some cases can kill the parasite. However, the Bge cells do not kill the parasite in vitro. MethodsBge cells were transfected by electroporation with plasmid pCas-BgAIFx4, encoding the Cas9 nuclease and a guide RNA specific for exon 4 of the B. glabrata AIF (BgAIF) gene. Transcript levels for Cas9 and for BgAIF were monitored by quantitative reverse-transcription-PCR and, in parallel, adhesion of gene-edited Bge cells during co-culture with of schistosome sporocysts was assessed. ResultsGene knockout manipulation induced gene-disrupting indels, frequently 1-2 bp insertions and/or 8-30 bp deletions, at the programmed target site; a range from 9 to 17% of the copies of the BgAIF gene in the Bge population of cells were mutated. Transcript levels for BgAIF were reduced by up to 73% (49.5{+/-}20.2% S.D, P [≤] 0.05, n =12). Adherence by BgAIF gene-edited ({Delta}BgAIF) Bge to sporocysts diminished in comparison to wild type cells, although cell morphology did not change. Specifically, as scored by a semi-quantitative cell adherence index (CAI), fewer {Delta}BgAIF than control wild type cells adhered to sporocysts; control CAI, 2.66{+/-}0.10, {Delta}BgAIF, 2.30{+/-}0.22 (P [≤] 0.01). ConclusionThe findings supported the hypothesis that BgAIF plays a role in the adherence of B. glabrata hemocytes to sporocysts during schistosome infection in vitro. This demonstration of the activity of programmed gene editing will enable functional genomics approaches using CRISPR/Cas9 to investigate additional components of the snail-schistosome host-parasite relationship.

molecular biology↗