Pseudomonas aeruginosa Disrupts Caenorhabditis elegans Iron Homeostasis, Causing a Hypoxic Response and Death

Kirienko, Natalia V.; Kirienko, Daniel R.; Larkins-Ford, Jonah; Wählby, Carolina; Ruvkun, Gary; Ausubel, Frederick M.

doi:10.1016/j.chom.2013.03.003

Cited by 196 publications

(233 citation statements)

References 67 publications

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“…As our taxonomic survey of C. elegans habitats shows, nematodes encounter complex communities of microbessome beneficial, some detrimental, rather than a single species. Antagonistic bacteria that do not support optimal C. elegans growth rates or cause induction of stress reporters could produce a toxin or virulence factor that actively and perhaps potently suppresses C. elegans growth, or could fail to supply a key micro-or macronutrient [e.g., iron (32) or vitamins (33,34)]. Beneficial bacteria could either supply key nutrients or actively suppress C. elegans stress and immune responses.…”

Section: Resultsmentioning

confidence: 99%

Caenorhabditis elegans responses to bacteria from its natural habitats

Samuel

Rowedder

Braendle

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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362

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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,

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Section: Resultsmentioning

confidence: 99%

Caenorhabditis elegans responses to bacteria from its natural habitats

Samuel

Rowedder

Braendle

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

362

479

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“…This result may provide an explanation for the previous finding that the level of long-acyl AHLs is greatly reduced in cocultures as compared with P. aeruginosa pure cultures (Figure 3b). Kirienko et al (2013) demonstrated that P. aeruginosa does not require quorum-sensing pathways to kill Caenorhabditis elegans. Supporting a role for iron in P. aeruginosa pathogenesis, pyoverdine was found to be required to cause hypoxia and death in C. elegans.…”

Section: Interspecies Competition Triggers Virulencementioning

confidence: 99%

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

et al. 2014

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Inter-kingdom and interspecies interactions are ubiquitous in nature and are important for the survival of species and ecological balance. The investigation of microbe-microbe interactions is essential for understanding the in vivo activities of commensal and pathogenic microorganisms. Candida albicans, a polymorphic fungus, and Pseudomonas aeruginosa, a Gram-negative bacterium, are two opportunistic pathogens that interact in various polymicrobial infections in humans. To determine how P. aeruginosa affects the physiology of C. albicans and vice versa, we compared the proteomes of each species in mixed biofilms versus single-species biofilms. In addition, extracellular proteins were analyzed. We observed that, in mixed biofilms, both species showed differential expression of virulence proteins, multidrug resistance-associated proteins, proteases and cell defense, stress and iron-regulated proteins. Furthermore, in mixed biofilms, both species displayed an increase in mutability compared with monospecific biofilms. This characteristic was correlated with the downregulation of enzymes conferring protection against DNA oxidation. In mixed biofilms, P. aeruginosa regulates its production of various molecules involved in quorum sensing and induces the production of virulence factors (pyoverdine, rhamnolipids and pyocyanin), which are major contributors to the ability of this bacterium to cause disease. Overall, our results indicate that interspecies competition between these opportunistic pathogens enhances the production of virulence factors and increases mutability and thus can alter the course of hostpathogen interactions in polymicrobial infections.

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“…In addition, siderophores are important for acquiring iron from host iron storage proteins and the extracellular milieu, which facilitates microbial growth in this specific niche (2). Siderophores are key virulence factors in many pathosystems, including infection with Pseudomonas aeruginosa (1)(2)(3)(4). For example, mutants of P. aeruginosa with compromised pyoverdin biosynthesis exhibit attenuated pathogenesis in both C. elegans and in mice (3)(4)(5); despite this, the virulence mechanism(s) of siderophores remains unknown.…”

mentioning

confidence: 99%

Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa

Kirienko

Ausubel

Ruvkun

2015

Proc. Natl. Acad. Sci. U.S.A.

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189

193

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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

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Pseudomonas aeruginosa Disrupts Caenorhabditis elegans Iron Homeostasis, Causing a Hypoxic Response and Death

Cited by 196 publications

References 67 publications

Caenorhabditis elegans responses to bacteria from its natural habitats

Caenorhabditis elegans responses to bacteria from its natural habitats

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa

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