Abstract
The recognition of pathogens and subsequent activation of defense responses are critical for the survival of organisms. The nematode Caenorhabditis elegans recognizes pathogenic bacteria and elicits defense responses by activating immune pathways and pathogen avoidance. Here we show that chemosensation of phenazines produced by pathogenic Pseudomonas aeruginosa, which leads to rapid activation of DAF-7/TGF-β in ASJ neurons, is insufficient for the elicitation of pathogen avoidance behavior. Instead, intestinal infection and bloating of the lumen, which depend on the virulence of P. aeruginosa, regulates both pathogen avoidance and aversive learning by modulating not only the DAF-7/TGF-β pathway but also the G-protein coupled receptor NPR-1 pathway, which also controls aerotaxis behavior. Modulation of these neuroendocrine pathways by intestinal infection serves as a systemic feedback that enables animals to avoid virulent bacteria. These results reveal how feedback from the intestine during infection can modulate the behavior, learning, and microbial perception of the host.
Highlights
In nature, all organisms are continuously exposed to a complex environment and are under constant threat of attack by pathogenic microbes
Because P. aeruginosa-produced phenazines lead to induction of the neuromodulator DAF-7/TGF-b in the ASJ neuron pair (Meisel et al, 2014), we studied the role of phenazines in the elicitation of the pathogen avoidance behavior
Phenazine-1-carboxylic acid, the precursor of all other phenazines produced by P. aeruginosa, is synthesized from chorismate by Figure 1 continued photomicrographs of N2 animals exposed for 8 hr to E. coli lawns containing 20 mg of phenazine-1-carboxylic acid (PCA), 1-hydroxyphenazine (1-HPZ), pyocyanin (PYO), and phenazine-1-carboxamide (PCN)
Summary
All organisms are continuously exposed to a complex environment and are under constant threat of attack by pathogenic microbes. To ensure their survival, organisms must recognize pathogens and mount a robust defense in response to their attack. Olfactory chemosensory neurons and nociceptor sensory neurons detect bacterial toxins, quorum-sensing molecules, formyl peptides, and lipopolysaccharides through distinct molecular mechanisms that lead to rapid avoidance behaviors (Boillat et al, 2015; Chiu et al, 2013; Meseguer et al, 2014; Riviere et al, 2009; Tizzano et al, 2010; Yang and Chiu, 2017). A deeper understanding of the various mechanisms of pathogen avoidance has the potential to uncover conserved host defense responses that are important against pathogen infections
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