The neural basis of temperature-driven host seeking in the human threadworm Strongyloides stercoralis

Soil-transmitted parasitic nematodes infect approximately one billion people and are a major cause of morbidity worldwide. The infective larvae (iL3s) of these parasites actively search for hosts in a poorly understood, sensory-driven process that requires thermal cues. Here, we describe the neural basis of temperature-driven host seeking in parasitic nematodes using the human threadworm Strongyloides stercoralis. We show that S. stercoralis thermosensation is mediated by the AFD neurons, a thermosensory neuron class that is conserved between parasitic and free-living nematodes. We demonstrate that S. stercoralis AFD displays parasite-specific adaptations that enable both nonlinear and linear encoding of temperatures up to human body temperature. Furthermore, we describe a novel thermosensory behavior in which S. stercoralis iL3s generate spontaneous reversals of temperature preference at below-body temperatures. Finally, we identify three thermoreceptors selectively expressed in S. stercoralis AFD that display parasite-specific sensitivities to human body temperatures and likely enable temperature-driven host seeking by iL3s. Our results are the first direct evidence that the sensory neurons of soil-transmitted parasitic nematodes exhibit parasite-specific neural adaptations and sensory coding strategies that allow them to target human hosts, a finding with important implications for efforts to develop new therapeutic strategies for nematode control.

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Chemosensory mechanisms of host seeking and infectivity in skin-penetrating nematodes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1909710117 ◽

2020 ◽

Vol 117 (30) ◽

pp. 17913-17923 ◽

Cited By ~ 2

Author(s):

Spencer S. Gang ◽

Michelle L. Castelletto ◽

Emily Yang ◽

Felicitas Ruiz ◽

Taylor M. Brown ◽

...

Keyword(s):

Molecular Mechanisms ◽

Strongyloides Stercoralis ◽

Sensory Cues ◽

Ancylostoma Ceylanicum ◽

Free Living ◽

Infective Larvae ◽

Host Seeking ◽

Third Stage ◽

Olfactory Preferences ◽

Insight Into

Approximately 800 million people worldwide are infected with one or more species of skin-penetrating nematodes. These parasites persist in the environment as developmentally arrested third-stage infective larvae (iL3s) that navigate toward host-emitted cues, contact host skin, and penetrate the skin. iL3s then reinitiate development inside the host in response to sensory cues, a process called activation. Here, we investigate how chemosensation drives host seeking and activation in skin-penetrating nematodes. We show that the olfactory preferences of iL3s are categorically different from those of free-living adults, which may restrict host seeking to iL3s. The human-parasitic threadwormStrongyloides stercoralisand hookwormAncylostoma ceylanicumhave highly dissimilar olfactory preferences, suggesting that these two species may use distinct strategies to target humans. CRISPR/Cas9-mediated mutagenesis of theS. stercoralis tax-4gene abolishes iL3 attraction to a host-emitted odorant and prevents activation. Our results suggest an important role for chemosensation in iL3 host seeking and infectivity and provide insight into the molecular mechanisms that underlie these processes.

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Skin-penetrating nematodes exhibit life-stage-specific interactions with host-associated and environmental bacteria

BMC Biology ◽

10.1186/s12915-021-01153-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ivan N. Chavez ◽

Taylor M. Brown ◽

Adrien Assié ◽

Astra S. Bryant ◽

Buck S. Samuel ◽

...

Keyword(s):

Life Cycle ◽

Life Stage ◽

Behavioral Responses ◽

Strongyloides Stercoralis ◽

Amplicon Sequencing ◽

Ecological Niches ◽

Free Living ◽

Egg Hatching ◽

Host Seeking ◽

Environmental Bacteria

Abstract Background Skin-penetrating nematodes of the genus Strongyloides infect over 600 million people, posing a major global health burden. Their life cycle includes both a parasitic and free-living generation. During the parasitic generation, infective third-stage larvae (iL3s) actively engage in host seeking. During the free-living generation, the nematodes develop and reproduce on host feces. At different points during their life cycle, Strongyloides species encounter a wide variety of host-associated and environmental bacteria. However, the microbiome associated with Strongyloides species, and the behavioral and physiological interactions between Strongyloides species and bacteria, remain unclear. Results We first investigated the microbiome of the human parasite Strongyloides stercoralis using 16S-based amplicon sequencing. We found that S. stercoralis free-living adults have an associated microbiome consisting of specific fecal bacteria. We then investigated the behavioral responses of S. stercoralis and the closely related rat parasite Strongyloides ratti to an ecologically diverse panel of bacteria. We found that S. stercoralis and S. ratti showed similar responses to bacteria. The responses of both nematodes to bacteria varied dramatically across life stages: free-living adults were strongly attracted to most of the bacteria tested, while iL3s were attracted specifically to a narrow range of environmental bacteria. The behavioral responses to bacteria were dynamic, consisting of distinct short- and long-term behaviors. Finally, a comparison of the growth and reproduction of S. stercoralis free-living adults on different bacteria revealed that the bacterium Proteus mirabilis inhibits S. stercoralis egg hatching, and thereby greatly decreases parasite viability. Conclusions Skin-penetrating nematodes encounter bacteria from various ecological niches throughout their life cycle. Our results demonstrate that bacteria function as key chemosensory cues for directing parasite movement in a life-stage-specific manner. Some bacterial genera may form essential associations with the nematodes, while others are detrimental and serve as a potential source of novel nematicides.

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TRPA1 tunes mosquito thermotaxis to host temperatures

10.1101/027896 ◽

2015 ◽

Author(s):

Roman A Corfas ◽

Leslie B Vosshall

Keyword(s):

High Temperature ◽

Body Temperature ◽

Human Body ◽

Thermal Environment ◽

Ambient Air ◽

Body Temperatures ◽

Host Body ◽

Host Seeking ◽

Thermal Stimuli ◽

Body Heat

While most ectotherms thermotax only to regulate their temperature, female mosquitoes are attracted to human body heat during pursuit of a blood meal. Here we elucidate the basic rules of Aedes aegypti thermotaxis and test the function of candidate thermoreceptors in this important behavior. We show that host-seeking mosquitoes are maximally attracted to thermal stimuli approximating host body temperatures, seeking relative warmth while avoiding both relative cooling and stimuli exceeding host body temperature. We found that the cation channel TRPA1, in addition to playing a conserved role in thermoregulation and chemosensation, is required for this specialized host-selective thermotaxis in mosquitoes. During host-seeking, AaegTRPA1-/- mutants failed to avoid stimuli exceeding host temperature, and were unable to discriminate between host-temperature and high-temperature stimuli. TRPA1-dependent tuning of thermotaxis is likely critical for mosquitoes host-seeking in a complex thermal environment in which humans are warmer than ambient air, but cooler than surrounding sun-warmed surfaces.

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Transgenesis in Strongyloides and related parasitic nematodes: historical perspectives, current functional genomic applications and progress towards gene disruption and editing

Parasitology ◽

10.1017/s0031182016000391 ◽

2016 ◽

Vol 144 (3) ◽

pp. 327-342 ◽

Cited By ~ 31

Author(s):

J. B. LOK ◽

H. SHAO ◽

H. C. MASSEY ◽

X. LI

Keyword(s):

Developmental Regulation ◽

Strongyloides Stercoralis ◽

Parasitic Nematodes ◽

Adult Males ◽

Free Living ◽

Historical Perspectives ◽

Males And Females ◽

Shed Light ◽

Related Parasite ◽

F1 Generation

SUMMARYTransgenesis for Strongyloides and Parastrongyloides was accomplished in 2006 and is based on techniques derived for Caenorhabditis elegans over two decades earlier. Adaptation of these techniques has been possible because Strongyloides and related parasite genera carry out at least one generation of free-living development, with adult males and females residing in soil contaminated by feces from an infected host. Transgenesis in this group of parasites is accomplished by microinjecting DNA constructs into the syncytia of the distal gonads of free-living females. In Strongyloides stercoralis, plasmid-encoded transgenes are expressed in promoter-regulated fashion in the F1 generation following gene transfer but are silenced subsequently. Stable inheritance and expression of transgenes in S. stercoralis requires their integration into the genome, and stable lines have been derived from integrants created using the piggyBac transposon system. More direct investigations of gene function involving expression of mutant transgene constructs designed to alter intracellular trafficking and developmental regulation have shed light on the function of the insulin-regulated transcription factor Ss-DAF-16. Transgenesis in Strongyloides and Parastrongyloides opens the possibility of powerful new methods for genome editing and transcriptional manipulation in this group of parasites. Proof of principle for one of these, CRISPR/Cas9, is presented in this review.

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