<i>Caenorhabditis elegans</i>as a Model Host for<i>Staphylococcus aureus</i>Pathogenesis

Sifri, Costi D.; Begun, Jakob; Ausubel, Frederick M.; Calderwood, Stephen B.

doi:10.1128/iai.71.4.2208-2217.2003

Cited by 304 publications

(366 citation statements)

References 76 publications

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“…In contrast, relatively little is known about innate immunity in the nematode Caenorhabditis elegans. Recent work has shown that C. elegans is killed by a variety of bacterial and fungal pathogens, including Pseudomonas aeruginosa (4)(5)(6)(7)(8)(9)(10)(11)(12). When this experimental host-pathogen system was used, a forward genetic screen for C. elegans mutants exhibiting enhanced susceptibility to P. aeruginosa-mediated killing (Esp phenotype) identified two components of a mitogen-activated protein kinase (MAPK) signaling cascade, the MAPK kinase kinase, NSY-1, and the MAPK kinase, SEK-1, that are required for pathogen resistance (13).…”

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confidence: 99%

“…When this experimental host-pathogen system was used, a forward genetic screen for C. elegans mutants exhibiting enhanced susceptibility to P. aeruginosa-mediated killing (Esp phenotype) identified two components of a mitogen-activated protein kinase (MAPK) signaling cascade, the MAPK kinase kinase, NSY-1, and the MAPK kinase, SEK-1, that are required for pathogen resistance (13). RNA interference (RNAi) inactivation of pmk-1, the gene encoding the p38 MAPK that functions downstream of NSY-1 and SEK-1, also resulted in enhanced susceptibility to killing by bacterial pathogens (11,13), and immunoblot analysis showed diminished activation of PMK-1 in nsy-1 and sek-1 mutants. Furthermore, pathogen-elicited apoptosis in C. elegans depended on PMK-1 signaling (14).…”

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confidence: 99%

“…The requirement of the PMK-1 MAPK pathway for immunity to diverse pathogens [Gram-negative (13,14) and Gram-positive (11) bacteria] suggests that various upstream signaling inputs may converge on PMK-1. To further characterize the C. elegans innate immune response, we sought to identify factors that act upstream of PMK-1.…”

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Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

Liberati

Fitzgerald

Kim

et al. 2004

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

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The p38 mitogen-activated protein kinase pathway regulates innate immune responses in evolutionarily diverse species. We have previously shown that the Caenorhabditis elegans p38 mitogenactivated protein kinase, PMK-1, functions in an innate immune response pathway that mediates resistance to a variety of microbial pathogens. Here, we show that tir-1, a gene encoding a highly conserved Toll͞IL-1 resistance (TIR) domain protein, is also required for C. elegans resistance to microbial pathogens. RNA interference inactivation of tir-1 resulted in enhanced susceptibility to killing by pathogens and correspondingly diminished PMK-1 phosphorylation. Unlike all known TIR-domain adapter proteins, overexpression of the human TIR-1 homologue, SARM, in mammalian cells was not sufficient to induce expression of NF-B or IRF3-dependent reporter genes that are activated by Toll-like receptor signaling. These data reveal the involvement of a previously uncharacterized, evolutionarily conserved TIR domain protein in innate immunity that is functionally distinct from other known TIR domain signaling adapters.

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Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

Liberati

Fitzgerald

Kim

et al. 2004

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

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213

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“…Although mouse models have been used for these purposes, simpler invertebrates such as Caenorhabditis elegans have recently become more attractive for assessing the in vivo biological costs of antibiotic resistance (23,24). Many bacterial genes known to be required for mammalian pathogenesis are needed also in the nematode (1,9,11,15,16,27,28). Some bacterial pathogens, such as Salmonella enterica serovar Typhimurium are able to establish a persistent infection in the intestine of C. elegans, reducing the life span of the host.…”

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Caenorhabditis elegans as a Model To Determine Fitness of Antibiotic-Resistant Salmonella enterica Serovar Typhimurium

Paulander

Pennhag

Andersson

et al. 2007

Antimicrob Agents Chemother

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We used the ability of Salmonella enterica serovar Typhimurium to colonize the gut of Caenorhabditis elegans to measure the fitness costs imposed by antibiotic resistance mutations. The fitness costs determined in the nematode were similar to those measured in mice, validating its use as a simple host model to evaluate bacterial fitness.The persistence of antibiotic-resistant bacteria largely depends on the effect of the resistance mechanism on fitness (reviewed in references 3 and 4). The cost caused by resistance mutations can be decreased by second-site mutations that restore fitness without a loss of resistance (3,17,18). This process has been observed in many cases both in vitro (13,17,19,22,25) and in clinical settings (6,8,20,26). These findings suggest that antibiotic resistance may persist in the population for a long time and that the determination of fitness parameters is of great importance for predicting the risk of resistance development.Fitness costs are usually determined by comparing the growth rates of resistant and susceptible bacteria (3). Although mouse models have been used for these purposes, simpler invertebrates such as Caenorhabditis elegans have recently become more attractive for assessing the in vivo biological costs of antibiotic resistance (23, 24). Many bacterial genes known to be required for mammalian pathogenesis are needed also in the nematode (1,9,11,15,16,27,28). Some bacterial pathogens, such as Salmonella enterica serovar Typhimurium are able to establish a persistent infection in the intestine of C. elegans, reducing the life span of the host. Several genes needed for virulence in mammals are also required for pathogenesis in C. elegans (2,10,16,28), implying that the invasion and proliferation of serovar Typhimurium in the host intestine depend on mechanisms common to the nematode and mammals. This makes C. elegans a relevant model for determining the infectivity and fitness of antibiotic-resistant bacteria during a host infection.Virulence assays were performed as previously described (2) using C. elegans SS104 [glp-4 (ts)] (5), a temperature-sensitive mutant that produces progeny at 15°C but not at 25°C. At least 50 synchronized worms in larval stage L4 were transferred on solid nematode growth medium (NGM) (12) seeded with 10 l of serovar Typhimurium mixed 1:100 with the nonpathogenic Escherichia coli strain OP50 and maintained at 25°C. Both bacterial species grow on NGM agar with no mutual inhibition. The number of viable worms was monitored every day, and the percentages of nematode survival calculated by the KaplanMeier method (14) were used for plotting the percent survival as a function of time. Survival kinetics were compared by using the nonparametric log-rank test and were considered statistically different when P was Ͻ0.05. We found that the time to death for 50% of the nematodes was 9 days when fed with E. coli OP50 and 7 days after ingestion of the virulent wild-type strain LT2 of serovar Typhimurium (Fig. 1). As previously shown, the glp-4 (ts) strain resp...

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“…C. elegans has also been reported as a successful model for the investigation of virulence-associated factors of human pathogens such as Burkholderia pseudomallei 10) , Cryptococcus neoformans 19) , Enterococcus faecalis 27) , enteropathogenic Escherichia coli 2,16) , Listeria monocytogenes 34) , P. aeruginosa 32) , Serratia marcescens 14) , Shigella flexneri 6) , Staphylococcus aureus 11,28) , and Vibrio vulnificus 9) .…”

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Evaluation of Caenorhabditis elegans as the Host in an Infection Model for Food-borne Pathogens

香織¹,

智佳子²,

高紀³

et al. 2008

Jpn. J. Food Microbiol.

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The bacteriophagous nematode Caenorhabditis elegans has been recognized as a surrogate host for human pathogens. The aim of this study was to examine whether food-borne pathogens are pathogenic in nematodes. Young adult worms were allocated onto peptone-free medium covered with a bacterial suspension of each pathogen. The plates were incubated and as the number of live and dead worms scored at least every 24 h. Twelve of the 14 pathogenic strains, namely Aeromonas sobria, the diarrheagenic Escherichia coli strains (enteroaggregative E. coli, enterohemorrhagic E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, enteroaggregative E. coli heat-stable enterotoxin 1 gene-possessing E. coli, and di#usely adherent E. coli), Listeria monocytogenes, Salmonella Enteritidis, Staphylococcus aureus, Vibrio parahaemolyticus, and Yersinia enterocolitica reduced the survival rate of worms to varying degrees. The remaining 2 strains, Bacillus cereus and enteroinvasive E. coli, did not. Thus, food-borne pathogens can infect and proliferate within bacteriophagous nematodes on peptone-free medium to the same extent as reported with conventional peptone-containing medium. However, the non-enteropathogenic E. coli strain HS and deletion mutants of L. monocytogenes, which have lost their virulence in the murine model, were also still nematocidal. Although this nematode could be an alternative host for these pathogens, the nematocidal activity of these pathogens may not necessarily reflect enteropathogenicity in humans. Pathogens and the virulence genes to be analyzed must be carefully selected before using this alternative host.Key words: C. elegans, Enteric pathogen, Virulence, Screening, Infection model Introduction A variety of experimental models have been developed to study microbial virulence or the pathogenicity of protein toxins. However, due to increasing ethical considerations as well as economic reasons, the use of mammalian hosts is decreasing in popularity, and the establishment of e#ective alternative non-mammalian systems is urgently required.There has recently been increasing interest in the soil nematode Caenorhabditis elegans as a possible host of human pathogenic bacteria, since it was reported by Ausubel et al. in 1999 that Pseudomonas aeruginosa caused fatal infection of C. elegans 31) . C. elegans has also been reported as a successful model for the investigation of virulence-associated factors of human pathogens such as Burkholderia pseudomallei 10) , Cryptococcus neoformans 19) , Enterococcus faecalis 27) , enteropathogenic Escherichia coli 2, 16) , Listeria monocytogenes 34) , P. aeruginosa 32) , Serratia marcescens 14) , Shigella flexneri 6) , Staphylococcus aureus 11,28) , and Vibrio vulnificus 9) .We recognized nematodes as a potential new surrogate host, and the degree of similarity between this nematode, C. elegans, and humans is greater than expected 17) . In the above-cited reports, the human pathogens and associated ῍ Ί̮ ῌ558ῌ8585 ̮ῒ ̮ῐῑ̮Ὶ 3ῌ3ῌ138 ῖῚ̮Ῐῗ̮Ῑ῏῎ΐ Jpn.

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Caenorhabditis elegansas a Model Host forStaphylococcus aureusPathogenesis

Cited by 304 publications

References 76 publications

Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

Caenorhabditis elegans as a Model To Determine Fitness of Antibiotic-Resistant Salmonella enterica Serovar Typhimurium

Evaluation of Caenorhabditis elegans as the Host in an Infection Model for Food-borne Pathogens

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