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The Unique Life Cycle of Strongyloides stercoralis and Implications for Public Health Action.

ABSTRACT: Strongyloides stercoralis has one of the most complex life cycles of the human-infecting nematodes. A common misconception in medical and public health professions is that S. stercoralis in its biology is akin to other intestinal nematodes, such as the hookworms. Despite original evidence provided by medical and veterinary research about this unique helminth, many assumptions have entered the scientific literature. This helminth is set apart from others that commonly affect humans by (a) the internal autoinfective cycle with autoinfective larvae randomly migrating through tissue, parthenogenesis, and the potential for lifelong infection in the host, the profound pathology occurring in hyperinfection and systemic manifestations of strongyloidiasis, and (b) a limited external cycle with a single generation of free-living adults. This paper aims to review and discuss original research on the unique life cycle of S. stercoralis that distinguishes it from other helminths and highlight areas where increased understanding of the parasite's biology might lead to improved public health prevention and control strategies.

SUBMITTER: Page W

PROVIDER: S-EPMC6073624 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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The Unique Life Cycle of Strongyloides stercoralis and Implications for Public Health Action.

Page Wendy W Judd Jenni A JA Bradbury Richard S RS

Tropical medicine and infectious disease 20180525 2

<i>Strongyloides stercoralis</i> has one of the most complex life cycles of the human-infecting nematodes. A common misconception in medical and public health professions is that <i>S. stercoralis</i> in its biology is akin to other intestinal nematodes, such as the hookworms. Despite original evidence provided by medical and veterinary research about this unique helminth, many assumptions have entered the scientific literature. This helminth is set apart from others that commonly affect humans ...[more]

PMID: 30274449

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Project description:The complex life cycle of the parasitic nematode Strongyloides stercoralis leads to either developmental arrest of infectious third-stage larvae (iL3) or growth to reproductive adults. In the free-living nematode Caenorhabditis elegans, analogous determination between dauer arrest and reproductive growth is governed by dafachronic acids (DAs), a class of steroid hormones that are ligands for the nuclear hormone receptor DAF-12. Biosynthesis of DAs requires the cytochrome P450 (CYP) DAF-9. We tested the hypothesis that DAs also regulate S. stercoralis development via DAF-12 signaling at three points. First, we found that 1 ?M ?7-DA stimulated 100% of post-parasitic first-stage larvae (L1s) to develop to free-living adults instead of iL3 at 37°C, while 69.4±12.0% (SD) of post-parasitic L1s developed to iL3 in controls. Second, we found that 1 ?M ?7-DA prevented post-free-living iL3 arrest and stimulated 85.2±16.9% of larvae to develop to free-living rhabditiform third- and fourth-stages, compared to 0% in the control. This induction required 24-48 hours of ?7-DA exposure. Third, we found that the CYP inhibitor ketoconazole prevented iL3 feeding in host-like conditions, with only 5.6±2.9% of iL3 feeding in 40 ?M ketoconazole, compared to 98.8±0.4% in the positive control. This inhibition was partially rescued by ?7-DA, with 71.2±16.4% of iL3 feeding in 400 nM ?7-DA and 35 ?M ketoconazole, providing the first evidence of endogenous DA production in S. stercoralis. We then characterized the 26 CYP-encoding genes in S. stercoralis and identified a homolog with sequence and developmental regulation similar to DAF-9. Overall, these data demonstrate that DAF-12 signaling regulates S. stercoralis development, showing that in the post-parasitic generation, loss of DAF-12 signaling favors iL3 arrest, while increased DAF-12 signaling favors reproductive development; that in the post-free-living generation, absence of DAF-12 signaling is crucial for iL3 arrest; and that endogenous DA production regulates iL3 activation.

Dataset Information

The Unique Life Cycle of Strongyloides stercoralis and Implications for Public Health Action.

Publications

The Unique Life Cycle of Strongyloides stercoralis and Implications for Public Health Action.

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