Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, which is sensed by SRB-6. This behavioral adaptation represents an important strategy for the nematode, which utilizes specialized sensory organs and a chemoreceptor that is tuned to recognize the bacteria. These findings provide a window into the molecules and organs used in the coevolutionary arms race between predator and potential prey.
Amyloids are a class of protein aggregates that have been historically characterized by their relationship with human disease. Indeed, amyloids can be the result of misfolded proteins that self-associate to form insoluble, extracellular plaques in diseased tissue. For the first 150 years of their study, the pathogen-first definition of amyloids was sufficient. However, new observations of amyloids foster an appreciation for non-pathological roles for amyloids in cellular systems. There is now evidence from all domains of life that amyloids can be non-pathogenic and functional, and that their formation can be the result of purposeful and controlled cellular processes. So-called functional amyloids fulfill an assortment of biological functions including acting as structural scaffolds, regulatory mechanisms, and storage mechanisms. The conceptual convergence of amyloids serving a functional role has been repeatedly confirmed by discoveries of additional functional amyloids. With dozens already known, and with the vigorous rate of discovery, the biology of amyloids is robustly represented by non-pathogenic amyloids.
Many organisms produce "functional" amyloid fibers, which are stable protein polymers that serve many roles in cellular biology. Certain Enterobacteriaceae assemble functional amyloid fibers called curli that are the main protein component of the biofilm extracellular matrix. CsgA is the major protein subunit of curli and will rapidly adopt the polymeric amyloid conformation in vitro. The rapid and irreversible nature of CsgA amyloid formation makes it challenging to study in vitro. Here, we engineered CsgA so that amyloid formation could be tuned to the redox state of the protein. A double cysteine variant of CsgA called CsgA CC was created and characterized for its ability to form amyloid. When kept under oxidizing conditions, CsgA CC did not adopt a β-sheet rich structure or form detectable amyloid-like aggregates. Oxidized CsgA CC remained in a soluble, non-amyloid state for at least 90 days. The addition of reducing agents to CsgA CC resulted in amyloid formation within hours. The amyloid fibers formed by CsgA CC were indistinguishable from the fibers made by CsgA WT. When measured by thioflavin T fluorescence the amyloid formation by CsgA CC in the reduced form displayed the same lag, fast, and plateau phases as CsgA WT. Amyloid formation by CsgA CC could be halted by the addition of oxidizing agents. Therefore, CsgA CC serves as a proof-of-concept for capitalizing on the convertible nature of disulfide bonds to control the aggregation of amyloidogenic proteins.
Species of the non‐motile bacterium Streptomyces protect themselves from predation by the bacteriovore Caenorhabditis elegans through the secretion of nematicides. To evade death by these agents, C. elegans has evolved the ability to detect and avoid the bacterium. We characterize fatty acid analogs, including dodecanoic acid, which elicit a fast avoidance response by C. elegans. We also detect dodecanoic acid that has been secreted by Streptomyces by derivatization and detection with high resolution mass spectrometry. By sensing these signals, C. elegans can escape the nematicidal bacteria that would otherwise be a good food source.Support or Funding InformationLaura Miller Conrad: National Institutes of Health (5SC3GM118199); Angelina Tang and Sarah Matthews: National Science Foundation (HRD‐1302873); Miri VanHoven: National Institutes of Health (NS087544, GM089595), National Science Foundation (1355202).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pseudomonas aeruginosa is an opportunistic Gram-negative bacteria capable of causing severe infectious disease. Due to its rugged defenses and ability to acquire antibiotic resistance, a new strategy of fighting P. aeruginosa infection is necessary. Unlike antibiotics, antivirulence therapeutics disarm bacteria and make them less virulent instead of affecting their growth. One antivirulence strategy is to target quorum sensing, a signaling pathway that controls many virulence genes in P. aeruginosa. Quorum sensing is triggered by a signal molecule produced by the synthase enzyme LasI. We synthesized a small collection of inhibitors designed to competitively inhibit LasI thereby disrupting quorum sensing and allow a host's immune system to better combat a non-virulent P. aeruginosa infection. Caenorhabditis elegans is a soil dwelling nematode and a model organism for understanding metazoan nervous systems. Phasmids are sensory organs found in the posterior of the animal. Hilliard and coworkers discovered the phasmid neuron PHB's ability to enable chemorepulsion. C. elegans was observed exhibiting a strong avoidance response to sodium dodecyl sulfate. We hypothesize this response is unnatural and is instead the result of an evolutionarily developed avoidance to fatty acids secreted by Streptomyces avermitilis. S. avermitilis is a species of soil bacteria made famous for the Nobel Prize awarded to the scientists that isolated Avermectin, a potent nematocidal drug. It is clear S. avermitilis secretes metabolites that nematodes would benefit from avoiding. We identified the presence of decanoic and dodecanoic acid in S. avermitilis cell free supernatant and confirmed C. elegans avoidance response is triggered in similar magnitude to these compounds.
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