Biology subjects

Bryant, A. S.

Publications and source records attributed to Bryant, A. S..

6 recordsLinked to original sources

bioRxiv2025

Dopamine signaling drives skin invasion by human-infective nematodes

Skin-penetrating nematodes are one of the most prevalent causes of disease worldwide - nearly 15% of the global population is infected with at least one species of skin-penetrating nematode1,2. The World Health Organization has targeted these parasites for elimination by 20303, but the lack of preventative measures is a major obstacle to this goal. The infective larvae of skin-penetrating nematodes enter hosts through skin4, and blocking skin penetration is an as-yet unexplored approach for preventing infection. However, in order to prevent worm ingress via the skin, an understanding of the behavioral and neural mechanisms that drive skin penetration is required. Here, we describe the skin-penetration behaviors of the human-infective threadworm Strongyloides stercoralis. Using fluorescently labeled worms to enable visualization on the skin coupled with time-lapse microscopy, we show that S. stercoralis engages in repeated cycles of pushing, puncturing, and crawling on the skin surface before penetrating the skin. Pharmacological inhibition of dopamine signaling inhibits these behaviors in S. stercoralis and the human hookworm Ancylostoma ceylanicum, suggesting a critical role for dopamine signaling in driving skin penetration across distantly related nematodes. CRISPR-mediated disruption of dopamine biosynthesis and chemogenetic silencing of dopaminergic neurons also inhibit skin penetration. Finally, inactivation of the TRPN channel TRP-4, which is expressed in the dopaminergic neurons, blocks skin penetration on both rat and human skin. Our results suggest that drugs targeting TRP-4 and other nematode-specific components of the dopaminergic pathway could be developed into topical prophylactics that block skin penetration, thereby preventing infections.

neuroscience↗

bioRxiv2024

Thermosensory behaviors of the free-living life stages of Strongyloides species support parasitism in tropical environments

Soil-transmitted parasitic nematodes infect over 1 billion people worldwide and are a common source of neglected disease. Strongyloides stercoralis is a potentially fatal skin-penetrating human parasite that is endemic to tropical and subtropical regions around the world. The complex life cycle of Strongyloides species is unique among human-parasitic nematodes in that it includes a single free-living generation featuring soil-dwelling, bacterivorous adults whose progeny all develop into infective larvae. The sensory behaviors that enable free-living Strongyloides adults to navigate and survive soil environments are unknown. S. stercoralis infective larvae display parasite-specific sensory-driven behaviors, including robust attraction to mammalian body heat. In contrast, the free-living model nematode Caenorhabditis elegans displays thermosensory behaviors that guide adult worms to stay within a physiologically permissive range of environmental temperatures. Do S. stercoralis and C. elegans free-living adults, which experience similar environmental stressors, display common thermal preferences? Here, we characterize the thermosensory behaviors of the free-living adults of S. stercoralis as well as those of the closely related rat parasite, Strongyloides ratti. We find that Strongyloides free-living adults are exclusively attracted to near-tropical temperatures, despite their inability to infect mammalian hosts. We further show that lifespan is shorter at higher temperatures for free-living Strongyloides adults, similar to the effect of temperature on C. elegans lifespan. However, we also find that the reproductive potential of the free-living life stage is enhanced at warmer temperatures, particularly for S. stercoralis. Together, our results reveal a novel role for thermotaxis to maximize the infectious capacity of obligate parasites and provide insight into the biological adaptations that may contribute to their endemicity in tropical climates. Author SummarySoil-transmitted parasitic nematodes infect over 1 billion people and are a major source of neglected disease, particularly in the worlds most resource-limited communities. For most parasitic nematode species, reproductive adults exclusively reside within host animals. Species in the genus Strongyloides have a unique step in their life cycle that features soil-dwelling, non-parasitic adults. Previous studies of the free-living model nematode Caenorhabditis elegans have identified temperature as an important factor in ability of free-living nematodes to survive and reproduce in the environment. Our study investigates how the thermosensory behaviors of Strongyloides free-living adults contribute to their survival as well as their role in amplifying the quantity of infective larvae in the soil. We show that Strongyloides free-living adults display broad thermophilic preferences that are highly distinct from those of C. elegans adults. We also present the first evidence that thermotaxis acts as a robust mechanism for maximizing the infectious capacity of Strongyloides species located in tropical climates.

neuroscience↗

bioRxiv2021

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 worldwide1-8. The infective larvae (iL3s) of these parasites actively search for hosts in a poorly understood, sensory-driven process that requires thermal cues9,10. 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 nematodes11. 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.

neuroscience↗

bioRxiv2021

Manganese transport by Streptococcus sanguinis in acidic conditions and its impact on growth in vitro and in vivo

Streptococcus sanguinis is an oral commensal and an etiological agent of infective endocarditis. Previous studies have identified the SsaACB manganese transporter as essential for endocarditis virulence; however, the significance of SsaACB in the oral environment has never been examined. Here we report that a {Delta}ssaACB mutant of strain SK36 exhibits reduced growth and manganese uptake under acidic conditions. Further studies revealed that these deficits resulted from the decreased activity of TmpA, shown in the accompanying paper to function as a ZIP-family manganese transporter. Transcriptomic analysis of fermentor-grown cultures of SK36 WT and {Delta}ssaACB strains identified pH-dependent changes related to carbon catabolite repression in both strains, though their magnitude was generally greater in the mutant. In strain VMC66, which possesses a MntH transporter, loss of SsaACB did not significantly alter growth or cellular manganese levels under the same conditions. Interestingly, there were only modest differences between SK36 and its {Delta}ssaACB mutant in competition with Streptococcus mutans in vitro and in a murine oral colonization model. Our results suggest that the heterogeneity of the oral environment may provide a rationale for the variety of manganese transporters found in S. sanguinis and point to strategies for enhancing the safety of oral probiotics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/446192v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@a5afa7org.highwire.dtl.DTLVardef@1af3cdforg.highwire.dtl.DTLVardef@1c58693org.highwire.dtl.DTLVardef@1063980_HPS_FORMAT_FIGEXP M_FIG Depiction of methods. Streptococcal strains used are depicted at the top. The four methods illustrated are: 1. S. sanguinis cells were grown in media at pH 7.3 and pH 6.2 and quantified by plating. 2. S. sanguinis cells were grown in a fermentor vessel for RNA-sequencing and metal analysis. 3. S. sanguinis and S. mutans cells were grown in 12-well plates singly or in competition, then plated and the pH of the media measured. 4. S. sanguinis and S. mutans cells were inoculated into the mouths of mice. Oral swabs and dental biofilms from molars were assayed for bacterial composition by qPCR. (Biorender) C_FIG

microbiology↗

bioRxiv2021

The Wild Worm Codon Adapter: a web tool for automated codon adaptation of transgenes for expression in non-Caenorhabditis nematodes

Advances in genomics techniques are expanding the range of nematode species that are amenable to transgenesis. Due to divergent codon usage biases across species, codon optimization is often a critical step for the successful expression of exogenous transgenes in nematodes. Platforms for generating DNA sequences codon optimized for the free-living model nematode Caenorhabditis elegans are broadly available. However, until now such tools did not exist for non-Caenorhabditis nematodes. We therefore developed the Wild Worm Codon Adapter, a tool for rapid transgene codon optimization for expression in non-Caenorhabditis nematodes. The app includes built-in optimization for parasitic nematodes in the Strongyloides, Nippostrongylus and Brugia genera as well as the predatory nematode Pristionchus pacificus. The app also supports custom optimization for any species using user-provided optimization rules. In addition, the app supports automated insertion of synthetic or native introns, as well as the analysis of codon bias in transgene and native sequences. Here, we describe this web-based tool and demonstrate how it may be used to analyze genome-wide codon bias in Strongyloides species.

bioinformatics↗

bioRxiv2021

Strongyloides RNA-seq Browser: a web-based software platform for on-demand bioinformatics analyses of Strongyloides species

Soil-transmitted gastrointestinal parasitic nematodes infect approximately 1 billion people worldwide, predominantly in low-resource communities. Skin-penetrating gastrointestinal nematodes in the genus Strongyloides are emerging as model systems for mechanistic studies of soil-transmitted helminths due to the growing availability of functional genomics tools for these species. To facilitate future genomics studies of Strongyloides species, we have designed a web-based application, the Strongyloides RNA-seq Browser, that provides an open source, user-friendly portal for accessing and analyzing Strongyloides genomic expression data. Specifically, the Strongyloides RNA-seq Browser takes advantage of alignment-free read mapping tools and R-based transcriptomics tools to re-analyze publicly available RNA sequencing datasets from four Strongyloides species: Strongyloides stercoralis, Strongyloides ratti, Strongyloides papillosus, and Strongyloides venezuelensis. This application permits on-demand exploration and quantification of gene expression across life stages without requiring previous coding experience. Here, we describe this interactive application and demonstrate how it may be used by nematode researchers to conduct a standard set of bioinformatics queries.

bioinformatics↗