Take a Walk to the Wild Side of Caenorhabditis elegans-Pathogen Interactions

Abstract

Microbiomes form intimate functional associations with their hosts. Much has been learned from correlating changes in microbiome composition to host organismal functions. However, in-depth functional studies require the manipulation of microbiome composition coupled with the precise interrogation of organismal physiology-features available in few host study systems. Caenorhabditis elegans has proven to be an excellent genetic model organism to study innate immunity and, more recently, microbiome interactions. The study of C. elegans-pathogen interactions has provided in depth understanding of innate immune pathways, many of which are conserved in other animals. However, many bacteria were chosen for these studies because of their convenience in the lab setting or their implication in human health rather than their native interactions with C. elegans In their natural environment, C. elegans feed on a variety of bacteria found in rotting organic matter, such as rotting fruits, flowers, and stems. Recent work has begun to characterize the native microbiome and has identified a common set of bacteria found in the microbiome of C. elegans While some of these bacteria are beneficial to C. elegans health, others are detrimental, leading to a complex, multifaceted understanding of bacterium-nematode interactions. Current research on nematode-bacterium interactions is focused on these native microbiome components, both their interactions with each other and with C. elegans We will summarize our knowledge of bacterial pathogen-host interactions in C. elegans, as well as recent work on the native microbiome, and explore the incorporation of these bacterium-nematode interactions into studies of innate immunity and pathogenesis.

Keywords: Caenorhabditis elegans; host-pathogen interactions; innate immunity; microbiome.

FIG 1

Dynamic interactions between C. elegans and bacteria. The C. elegans response to bacteria involves interactions among three response types: neuronal, nutritional, and pathogenic. The overlapping shifts from predator-prey to pathogen-host as C. elegans age are also shown.

FIG 2

Overview of innate immune and defense pathways: the TGF-β pathway, DAF-2/16 insulin-like pathway, p38 MAPK pathway, and unfolded protein response (UPR) pathway. Purple indicates ligands, blue indicates receptors, gray indicates downstream signaling components, and gold indicates transcription factors. Boxes below pathways identify selected major downstream effectors (65, 80, 82, 83, 86, 88, 93, 96, 99, 104, 109). DAG, diacylglycerol; TF, transcription factor.

FIG 3

Functional analysis of C. elegans microbiome members. Functional analysis of bacteria representative of common families identified across C. elegans microbiomes (102) and CeMbio members (104). Mean relative abundance indicates the relative abundance of each bacterial family across 23 C. elegans isolates in samples from the natural environment (102). The beneficial/detrimental status was determined for each isolate (the number of isolates for each genus is indicated in parentheses) based on growth rate and induction of stress reporters of C. elegans upon exposure to each isolate (101). Colonization was calculated by analysis of the CFU in individual C. elegans intestines grown on each bacteria at 1 and 3 days of adulthood. Growth rate indicates time to adulthood of C. elegans upon exposure to each bacteria compared to E. coli OP50 (104). The dot size represents the value for each functional assay, green indicates the beneficial/higher growth rate, red indicates detrimental/lower growth rate, and black indicates similarity to OP50. ND, no data. See references (Zhang et al. 2017), (Samuel et al. 2016), and (Dirksen et al. 2020).