Caenorhabditis elegans is a model host for Salmonella typhimurium

Abstract

The idea of using simple, genetically tractable host organisms to study the virulence mechanisms of pathogens dates back at least to the work of Darmon and Depraitère [1]. They proposed using the predatory amoeba Dictyostelium discoideum as a model host, an approach that has proved to be valid in the case of the intracellular pathogen Legionella pneumophila [2]. Research from the Ausubel laboratory has clearly established the nematode Caenorhabditis elegans as an attractive model host for the study of Pseudomonas aeruginosa pathogenesis [3]. P. aeruginosa is a bacterium that is capable of infecting plants, insects and mammals. Other pathogens with a similarly broad host range have also been shown to infect C. elegans [3,4]. Nevertheless, the need to determine the universality of C. elegans as a model host, especially with regards pathogens that have a naturally restricted host specificity, has rightly been expressed [5]. We report here that the enterobacterium Salmonella typhimurium, generally considered to be a highly adapted pathogen with a narrow range of target hosts [6], is capable of infecting and killing C. elegans. Furthermore, mutant strains that exhibit a reduced virulence in mammals were also attenuated for their virulence in C. elegans, showing that the nematode may constitute a useful model system for the study of this important human pathogen.

Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium -mediated killing

“…Salmonella typhimurium, Serratia marcescens, and Burkholderia pseudomallei, kill the nematode Caenorhabditis elegans when supplied as a food source, and a variety of bacterial virulence factors have been shown to play a role in both nematode and mammalian pathogenesis (1)(2)(3)(4)(5)(6). In addition, C. elegans mutants that are either more susceptible or more resistant to bacterial killing can be readily identified (7,8).…”

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

“…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).…”

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

“…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.…”

“…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.…”

“…The competition model correlated well with the mouse model, further supporting the notion that similar factors in serovar Typhimurium are required for growth in C. elegans and mice. For example, mutations in the genes fur-1, ompR, or rpoS involved in serovar Typhimurium acid tolerance important for virulence in mammals show attenuated virulence in C. elegans (16). Similarly, the PhoP/Q signal transduction system and several of the genes located in the pathogenicity island 1 are required for virulence in both mammals and C. elegans (2,10).…”