Antimicrobial effectors in the nematode Caenorhabditis elegans : an outgroup to the Arthropoda

Abstract

One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Nematodes and arthropods likely form the taxon Ecdysozoa. Information on antimicrobial effectors from the model nematode Caenorhabditis elegans may thus shed light on the evolutionary origin of these defences in arthropods. This nematode species possesses an extensive armory of putative antimicrobial effector proteins, such as lysozymes, caenopores (or saposin-like proteins), defensin-like peptides, caenacins and neuropeptide-like proteins, in addition to the production of reactive oxygen species and autophagy. As C. elegans is a bacterivore that lives in microbe-rich environments, some of its effector peptides and proteins likely function in both digestion of bacterial food and pathogen elimination. In this review, we provide an overview of C. elegans immune effector proteins and mechanisms. We summarize the experimental evidence of their antimicrobial function and involvement in the response to pathogen infection. We further evaluate the microbe-induced expression of effector genes using WormExp, a recently established database for C. elegans gene expression analysis. We emphasize the need for further analysis at the protein level to demonstrate an antimicrobial activity of these molecules both in vitro and in vivo.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

“…Indeed, it is well established that histidine, glutamic acid and aspartic acid residues have a strong potential for α-helical formation that is enhanced by low pH [98,292]. The pore forming antimicrobial proteins reviewed here are strongly α-helical (Figure 2) and it is known that changes to the levels of α-helical architecture possessed by these proteins are enhanced by low pH, which promotes their pore forming mechanisms and are key to their ability to kill microbes [35,82,84,89]. A full description of these conformational changes is beyond the scope of this review but as an example, the protonation of C-terminal histidine residues by low pH promotes conformational changes that lead to the construction of hexameric membrane pores via the formation of active dimers from inactive monomers in the case of amoebapores [79,81,231] caenopores [85,86,87,88,89] and psoriasin [34,35,36].…”

“…At neutral pH, acanthaporin appears to exist as an inactive dimer but low pH triggers the histidine mediated production of monomers and the formation of membrane pores, which promoted the activity of the peptide against a variety of bacteria [84]. Caenopores, also known as saposin-like proteins (SPP), are cystein stabilized helical proteins that are found in the nematode, Caenorhabditis elegans [89,232,233,234,235] and are distantly related to amoebapores with which they share structural and functional features [85,88,236,237]. Many of the genes encoding SPP proteins in C. elegans are induced in response to microbial challenge [232] and several of their gene products have been reported to exhibit pH dependent antimicrobial activity, including SSP-1 [85,86], SPP-3 [87], SPP-5 [88] and SPP-12 [86].…”

“…For each of these proteins, antimicrobial activity appeared to be based on an ability to form pores in membranes of target organisms under acid pH conditions and it was suggested that this ability was mediated by the multiple internal histidine residues possessed by caenopores. Due to these residues, the positive charge of these proteins is enhanced under acid conditions, increasing the potential for interaction with anionic components of microbial membranes and possibly mediating pore formation, as described for amoebapores [86,87,88,89,236,237]. It was observed that the pH dependent activity of these proteins would appear to reflect the pH conditions at the site of their functional action, such as SPP-1 and SPP-5, which are active in the acidic environment of the C. elegans intestine [88,89,236,237].…”

Caenorhabditis elegans as a Model for Microbiome Research

“…Due to these advantages, C. elegans has been used extensively for studying host-pathogen interactions, including mostly bacterial pathogens, but also fungi, microsporidia and viruses. This work has expanded our understanding of mechanism of innate immunity (Meisel and Kim, 2014; Cohen and Troemel, 2015; Dierking et al, 2016; Ewbank and Pujol, 2016; Kim and Ewbank, 2016). More recent work addressed the nematode's interactions with putative commensal and probiotic bacteria, such as Comamonas, Bacillus subtilis, Lactobacillus , and Bifidobacterium , yielding new insights into the mechanisms by which bacteria or their metabolites influence signaling, metabolism and life-history in the C. elegans host (reviewed in Clark and Hodgkin, 2014).…”

GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens

“…Several transcription factors have been found to contribute to C. elegans immune defence, such as the GATA transcription factor ELT-2 (Shapira et al, 2006), the basic-region leucine zipper (bZIP) transcription factors ATF-7 (Shivers et al, 2010), ATFS-1 (Pellegrino et al, 2014), ZIP-2 (Estes et al, 2010), and SKN-1 (Papp et al, 2012), the basic helix-loop-helix (bHLH) transcription factor HLH-30 (Visvikis et al, 2014), the signal transducer and activator of transcription (STAT)-like transcription factor STA-2 (Dierking et al, 2011), and the activator protein 1 (AP-1) transcription factor dimer JUN-1/FOS-1 (Kao et al, 2011). Moreover, pathogen elimination involves certain antimicrobial peptides (reviewed in Dierking et al, 2016), including, for example, the caenacins and related peptides (Couillault et al, 2004), the caenopores (Mysliwy et al, 2010;Roeder et al, 2010), and additionally the generation of reactive oxygen species (ROS) (Chávez et al, 2009;Van Der Hoeven et al, 2011). While it remains unclear if and how pathogens are directly recognized by C. elegans, nematode defence can also be activated indirectly through a cellular surveillance system and/or damage signals, allowing the worms to respond to the cellular disturbance caused by an infection (Melo and Ruvkun, 2012;Zugasti et al, 2014;Ewbank and Pujol, 2016).…”