Pore worms: Using Caenorhabditis elegans to study how bacterial toxins interact with their target host

Huffman, Danielle L.; Bischof, Larry J.; Griffitts, Joel S.; Aroian, Raffi V.

doi:10.1078/1438-4221-00303

Cited by 51 publications

(37 citation statements)

References 58 publications

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“…The role of PFTs is unlikely to be rapid cell lysis, because most mammalian cells do not rapidly swell and lyse when treated with low (physiological) concentrations of PFTs but rather stay viable for many hours (the toxins are, however, cytolytic at higher concentrations) (1). Interestingly, different cell types treated with different PFTs can display similar physiological responses, e.g., increases in cytosolic Ca 2ϩ and vacuolization, implying some conserved and possibly concerted responses (1)(2)(3)(4). However, the functional significance of these responses is uncertain; they could promote pathogenesis or cellular defenses or promote both or neither.…”

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confidence: 99%

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Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins

Huffman

Abrami²,

Šášik³

et al. 2004

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

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308

385

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Cytolytic pore-forming toxins are important for the virulence of many disease-causing bacteria. How target cells molecularly respond to these toxins and whether or not they can mount a defense are poorly understood. By using microarrays, we demonstrate that the nematode Caenorhabditis elegans responds robustly to Cry5B, a member of the pore-forming Crystal toxin family made by Bacillus thuringiensis. This genomic response is distinct from that seen with a different stressor, the heavy metal cadmium. A p38 mitogen-activated protein kinase (MAPK) kinase and a c-Jun N-terminal-like MAPK are both transcriptionally up-regulated by Cry5B. Moreover, both MAPK pathways are functionally important because elimination of either leads to animals that are (i) hypersensitive to a low, chronic dose of toxin and (ii) hypersensitive to a high, brief dose of toxin such that the animal might naturally encounter in the wild. These results extend to mammalian cells because inhibition of p38 results in the hypersensitivity of baby hamster kidney cells to aerolysin, a pore-forming toxin that targets humans. Furthermore, we identify two downstream transcriptional targets of the p38 MAPK pathway, ttm-1 and ttm-2, that are required for defense against Cry5B. Our data demonstrate that cells defend against pore-forming toxins by means of conserved MAPK pathways.

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confidence: 99%

“…[1][2][3][4]. Prominent examples of PFTs that attack human cells include cholesterol-dependent cytolysins (e.g., Streptococcus pyogenes streptolysin O), repeats in toxin cytolysins (e.g., Escherichia coli ␣-hemolysin), Aeromonas hydrophila aerolysin, Staphylococcus aureus ␣-toxin, and Vibrio cholerae hemolysin.…”

mentioning

confidence: 99%

Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins

Huffman

Abrami²,

Šášik³

et al. 2004

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

Self Cite

308

385

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“…Caenorhabditis elegans, a freeliving soil nematode that feeds primarily on bacteria (10), possesses important attributes, permitting it to serve as a model host to address such questions. Its rapid generation time, ease of propagation, well-defined cell lineage, fully sequenced genome containing a large number of vertebrate orthologues (50), and genetic tractability has aided the study of many biological processes, including microbial pathogenesis (1,2,8,14,15,21,22,24,29,31,39,57) and immunity (26,30,32,36,40,41,52,55,56). C. elegans possesses evolutionarily conserved signaling pathways for innate immunity, especially those involving the DAF-2 insulin/IGF-Ilike receptor (12,19,20,48), p38 MAP kinase (37,38,58), and transforming growth factor ␤ (TGF-␤) (16,46), which regulate an array of antibacterial effector molecules, including lysozymes, lipases, and C-type lectins (18,26,47).…”

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confidence: 99%

Competition and Resilience between Founder and Introduced Bacteria in the Caenorhabditis elegans Gut

Portal-Celhay

Blaser

2012

Infect Immun

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The microbial communities that reside within the intestinal tract in vertebrates are complex and dynamic. In this report, we establish the utility of Caenorhabditis elegans as a model system for identifying the factors that contribute to bacterial persistence and for host control of gut luminal populations. We found that for N2 worms grown on mixed lawns of bacteria, Salmonella enterica serovar Typhimurium substantially outcompeted Escherichia coli, even when E. coli was initially present at 100-foldhigher concentrations. To address whether innate immunity affects the competition, the daf-2 and daf-16 mutants were studied; their total gut bacterial levels reflect overall capacity for colonization, but Salmonella outcompeted E. coli to an extent similar to wild-type worms. To address the role of virulence properties, Salmonella ⌬spi-1 ⌬spi-2 was used to compete with E. coli. The net differential was significantly less than that for wild-type Salmonella; thus, spi-1 spi-2 encodes C. elegans colonization factors. An E. coli strain with repeated in vivo passage had an enhanced ability to compete against an in vitro-passed E. coli strain and against Salmonella. Our data provide evidence of active competition for colonization niches in the C. elegans gut, as determined by bacterial factors and subject to in vivo selection.

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“…The underlying strategy created by Donkin and Dusenbery [315][316][317][318][319][320][321][322][323][324][325][326][327][328] has prompted to an institutionalized soil toxicological testing technique received in 2001 by the American Society for Testing and Materials and as of late the International Standards Organization in Europe (ISO 2007). The underlying extraction technique has been enhanced using transgenic strains of nematodes which takes into consideration GFP-named worms to be utilized that recognizes the worms being tried in soils from the vast quantities of indigenous species that are comparable in size and appearance.…”

Section: Strains Investigated Observations Referencesmentioning

confidence: 99%

Discovering Capacity in Novel Targets: C. Elegans as a Model Life Form in Toxicological Research

Ac¹,

Costa²,

Tec³

et al. 2017

J Clinic Toxicol

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The nematode Caenorhabditis elegans has risen as a critical creature show in different fields including neurobiology, formative science, and hereditary qualities. Qualities of this creature demonstrate that have added to its prosperity incorporate its hereditary manipulability, invariant and completely depicted formative program, all around portrayed genome, simplicity of support, short and productive life cycle, and little body estimate. These same elements have prompted to an expanding utilization of C. elegans in toxicology, both for robotic reviews and highthroughput screening approaches. We depict a portion of the exploration that has been completed in the territories of neurotoxicology, hereditary toxicology, and ecological toxicology, and additionally high-throughput tries different things with C. elegans including all inclusive screening for sub-atomic focuses of harmfulness and fast danger evaluation for new chemicals. We contend for an expanded part for C. elegans in supplementing other model frameworks in toxicological research.

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Pore worms: Using Caenorhabditis elegans to study how bacterial toxins interact with their target host

Cited by 51 publications

References 58 publications

Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins

Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins

Competition and Resilience between Founder and Introduced Bacteria in the Caenorhabditis elegans Gut

Discovering Capacity in Novel Targets: C. Elegans as a Model Life Form in Toxicological Research

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