bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans

Self Cite

188

193

In the arms race of bacterial pathogenesis, bacteria produce an array of toxins and virulence factors that disrupt core host processes. Hosts mitigate the ensuing damage by responding with immune countermeasures. The iron-binding siderophore pyoverdin is a key virulence mediator of the human pathogen Pseudomonas aeruginosa, but its pathogenic mechanism has not been established. Here we demonstrate that pyoverdin enters Caenorhabditis elegans and that it is sufficient to mediate host killing. Moreover, we show that iron chelation disrupts mitochondrial homeostasis and triggers mitophagy both in C. elegans and mammalian cells. Finally, we show that mitophagy provides protection both against the extracellular pathogen P. aeruginosa and to treatment with a xenobiotic chelator, phenanthroline, in C. elegans. Although autophagic machinery has been shown to target intracellular bacteria for degradation (a process known as xenophagy), our report establishes a role for authentic mitochondrial autophagy in the innate immune defense against P. aeruginosa.mitophagy | Pseudomonas | siderophore | innate immunity | C. elegans

“…4C). Consistent with this, ZIP-2-dependent genes (19) were up-regulated in liquid killing (Fig. 4D).…”

Section: Elegans Uses a Multifaceted Innate Immune Response To Liquidsupporting

confidence: 72%

Section: Elegans Uses a Multifaceted Innate Immune Response To Liquidmentioning

confidence: 99%

Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa

Kirienko

Ausubel

Ruvkun

2015

Self Cite

188

193

“…Several conserved transcription factors including GATA/ELT-2 (1), FOXO/DAF-16 (15), and bZIP/ZIP-2 (32) regulate the expression of immunity-related genes and protect C. elegans from lethal infection by P. aeruginosa (1,32). We found that disruption of ELT-2 rendered worms hypersusceptible to B. pseudomallei infection, indicating that ELT-2 also protects C. elegans from a lethal B. pseudomallei infection.…”

Section: Discussionmentioning

confidence: 79%

Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor

Lee

Wong

Chin

et al. 2013

Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.innate immunity | ubiquitin-proteosomal system

“…elegans Strains and Maintenance. N2-Bristol, Phsp-4::GFP, Phsp-6::GFP, Pgst-4:: GFP (acquired from the Caenorhabditis Genetics Center); PF35E2.5, Pclec-60::GFP, Pirg-1::GFP (gifts from F. Ausubel, Massachusetts General Hospital, Boston) (39)(40)(41). All strains were maintained on NGM plates (no antibiotics) spotted with E. coli OP50 at 20°C-22°C using standard protocols (42) unless otherwise noted.…”

Section: Methodsmentioning

confidence: 99%

Caenorhabditis elegans responses to bacteria from its natural habitats

Samuel

Rowedder

Braendle

et al. 2016

359

479

Most Caenorhabditis elegans studies have used laboratory Escherichia coli as diet and microbial environment. Here we characterize bacteria of C. elegans' natural habitats of rotting fruits and vegetation to provide greater context for its physiological responses. By the use of 16S ribosomal DNA (rDNA)-based sequencing, we identified a large variety of bacteria in C. elegans habitats, with phyla Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria being most abundant. From laboratory assays using isolated natural bacteria, C. elegans is able to forage on most bacteria (robust growth on ∼80% of >550 isolates), although ∼20% also impaired growth and arrested and/or stressed animals. Bacterial community composition can predict wild C. elegans population states in both rotting apples and reconstructed microbiomes: alpha-Proteobacteria-rich communities promote proliferation, whereas Bacteroidetes or pathogens correlate with nonproliferating dauers. Combinatorial mixtures of detrimental and beneficial bacteria indicate that bacterial influence is not simply nutritional. Together, these studies provide a foundation for interrogating how bacteria naturally influence C. elegans physiology.Caenorhabditis elegans | host-microbe interactions | ecology B iological organisms constantly live in contact with other organisms in a complex web of ecological interactions, which include prey-predator, host-parasite, competitive, or positive symbiotic relationships. Bacteria are now considered key players in multiple aspects of the biology of multicellular organisms (1-3). The richness and importance of these interactions were so far neglected because laboratory biology had succeeded in simplifying and standardizing the environment of the model organisms, providing in most cases a single microbe as a food source, and not necessarily even a naturally encountered one. The many aspects of organismal biology that were shaped by evolution in natural environments are thus undetectable in the artificial laboratory environment and can only be revealed in the presence of other interacting species. Examples include feeding behavior, metabolism of diverse natural food sources, interactions with natural pathogens that have shaped the organism's immune system, behavioral traits, and regulation of development and reproduction. At the genomic level, many individual genes may not be required in a standard laboratory environment but their role may be revealed by using more diverse and relevant environments (4, 5).The nematode Caenorhabditis elegans is a typical example of a model organism that has been disconnected from its natural ecology: although the species has been studied intensively in the laboratory for half a century, its habitat and natural ecology-what it naturally feeds on, its natural predators and pathogens,