Investigating development of infective stage larvae of filarial nematodes

Smith, Heidi L.

doi:10.2741/a570

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…infective larva following a bite of the arthropod vector (Smith, 2000). Traveling through subcutaneous tissue for several days, the larva does not complete development through L4 to adulthood until it reaches the lymphatic system.…”

Section: Discussionmentioning

confidence: 99%

Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans

et al. 2009

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In response to pheromone(s), Caenorhabditis elegans interrupts its reproductive life cycle and enters diapause as a stress-resistant dauer larva. This decision is governed by a complex system of neuronal and hormonal regulation. All the signals converge onto the nuclear hormone receptor DAF-12. A sterol-derived hormone, dafachronic acid (DA), supports reproductive development by binding to DAF-12 and inhibiting its dauer-promoting activity. Here, we identify a methyltransferase, STRM-1, that modulates DA levels and thus dauer formation. By modifying the substrates that are used for the synthesis of DA, STRM-1 can reduce the amount of hormone produced. Loss of STRM-1 function leads to elevated levels of DA and inefficient dauer formation. Sterol methylation was not previously recognized as a mechanism for regulating hormone activity. Moreover, the C-4 sterol nucleus methylation catalyzed by STRM-1 is unique to nematodes and thus could be a target for therapeutic strategies against parasitic nematode infections.

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Section: Discussionmentioning

confidence: 99%

Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans

et al. 2009

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“…It is generally believed that the host provides some development cues to the parasite . The dependency of parasite development on host environmental cues appears to be most pronounced in the infective stage of the parasite . Babu et al .…”

Section: Host–parasite Interaction Plays a Key Role In Disease Pathogmentioning

confidence: 99%

Lymphatic Filariasis: Perspectives on Lymphatic Remodeling and Contractile Dysfunction in Filarial Disease Pathogenesis

et al. 2013

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Lymphatic filariasis, one of the most debilitating diseases associated with the lymphatic system, affects over a hundred million people worldwide and manifests itself in a variety of severe clinical pathologies. The filarial parasites specifically target the lymphatics and impair lymph flow, which is critical for the normal functions of the lymphatic system in maintenance of body fluid balance and physiological interstitial fluid transport. The resultant contractile dysfunction of the lymphatics causes fluid accumulation and lymphedema, one of the major pathologies associated with filarial infection. In this review, we take a closer look at the contractile mechanisms of the lymphatics, its altered functions and remodeling during an inflammatory state and how it relates to the severe pathogenesis underlying a filarial infection. We further elaborate on the complex host parasite interactions, and molecular mechanisms contributing to the disease pathogenesis. The overall emphasis is on elucidating some of the emerging concepts and new directions that aim to harness the process of lymphangiogenesis or enhance contractility in a dysfunctional lymphatics, thereby restoring the fluid imbalance and mitigating the pathological conditions of lymphatic filariasis.

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“…This is due in part to the complex life cycles of these parasites. Some parasitic nematodes, such as the filarial worms B. malayi and Onchocerca volvulus, require both invertebrate and vertebrate hosts and are transmitted to humans when hematophagous arthropods take a blood meal (Devaney, 2006;Nelson, 1991;Smith, 2000). Skin-penetrating nematodes such as hookworms and threadworms have both freeliving stages that develop in the environment and parasitic life stages that live in mammalian hosts (Bryant and Hallem, 2018a,b;Gang and Hallem, 2016).…”

Section: Introductionmentioning

confidence: 99%

Recent advances in functional genomics for parasitic nematodes of mammals

Castelletto

Gang

Hallem

2020

Journal of Experimental Biology

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Human-parasitic nematodes infect over a quarter of the world's population and are a major cause of morbidity in low-resource settings. Currently available treatments have not been sufficient to eliminate infections in endemic areas, and drug resistance is an increasing concern, making new treatment options a priority. The development of new treatments requires an improved understanding of the basic biology of these nematodes. Specifically, a better understanding of parasitic nematode development, reproduction and behavior may yield novel drug targets or new opportunities for intervention such as repellents or traps. Until recently, our ability to study parasitic nematode biology was limited because few tools were available for their genetic manipulation. This is now changing as a result of recent advances in the large-scale sequencing of nematode genomes and the development of new techniques for their genetic manipulation. Notably, skin-penetrating gastrointestinal nematodes in the genus Strongyloides are now amenable to transgenesis, RNAi and CRISPR/Cas9-mediated targeted mutagenesis, positioning the Strongyloides species as model parasitic nematode systems. A number of other mammalian-parasitic nematodes, including the giant roundworm Ascaris suum and the tissue-dwelling filarial nematode Brugia malayi, are also now amenable to transgenesis and/or RNAi in some contexts. Using these tools, recent studies of Strongyloides species have already provided insight into the molecular pathways that control the developmental decision to form infective larvae and that drive the host-seeking behaviors of infective larvae. Ultimately, a mechanistic understanding of these processes could lead to the development of new avenues for nematode control.

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Investigating development of infective stage larvae of filarial nematodes

Cited by 6 publications

References 42 publications

Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans

Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans

Lymphatic Filariasis: Perspectives on Lymphatic Remodeling and Contractile Dysfunction in Filarial Disease Pathogenesis

Recent advances in functional genomics for parasitic nematodes of mammals

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