Natural C. elegans Microbiota Protects against Infection via Production of a Cyclic Lipopeptide of the Viscosin Group

Caenorhabditis elegans is associated in nature with a species-rich, distinct microbiota, which was characterized only recently [1]. Thus, our understanding of the relevance of the microbiota for nematode fitness is still at its infancy. One major benefit that the intestinal microbiota can provide to its host is protection against pathogen infection [2]. However, the specific strains conferring the protection and the underlying mechanisms of microbiota-mediated protection are often unclear [3]. Here, we identify natural C. elegans microbiota isolates that increase C. elegans resistance to pathogen infection. We show that isolates of the Pseudomonas fluorescens subgroup provide paramount protection from infection with the natural pathogen Bacillus thuringiensis through distinct mechanisms. We found that the P. lurida isolates MYb11 and MYb12 (members of the P. fluorescens subgroup) protect C. elegans against B. thuringiensis infection by directly inhibiting growth of the pathogen both in vitro and in vivo. Using genomic and biochemical analyses, we further demonstrate that MYb11 and MYb12 produce massetolide E, a cyclic lipopeptide biosurfactant of the viscosin group [4, 5], which is active against pathogenic B. thuringiensis. In contrast to MYb11 and MYb12, P. fluorescens MYb115-mediated protection involves increased resistance without inhibition of pathogen growth and most likely depends on indirect, host-mediated mechanisms. This work provides new insight into the functional significance of the C. elegans natural microbiota and expands our knowledge of bacteria-derived compounds that can influence pathogen colonization in the intestine of an animal. [Display omitted] •Natural C. elegans microbiota confer protection against pathogen infection•Different Pseudomonas isolates protect C. elegans through distinct mechanisms•P. lurida isolates produce massetolide E and directly inhibit pathogen growth•P. fluorescens-mediated protection may depend on indirect, host-mediated mechanisms Kissoyan et al. provide novel insights into the function of the native microbiota of the model nematode C. elegans. Their work highlights the role of microbes in supporting C. elegans defense responses and the diversity of immune-protective mechanisms, including the involvement of microbiota-derived metabolites.