Caenorhabditis elegans as a Model Organism for Host-Pathogen Interaction Studies

Written by : Mohd Azrul Hisham Ismail and Hui-min Neoh

Date Publish :  06 Disember 2022

UKM Medical Molecular Biology Institute (UMBI)

Caenorhabditis elegans as a Model Organism for Host-Pathogen Interaction Studies

 

Caenorhabditis elegans, a nematode, has been introduced into the laboratory from its natural habitat by Nobel Prize laureate, Sydney Brenner over 50 years ago (Corsi et al., 2015). Since then, C. elegans has piqued the interest of scientists to use this tiny organism as an animal research model. C. elegans is a unique organism because it is a free living nematode that can be found naturally in soil and compost heaps (Marsh & May, 2012). They are able to self-fertilize as they are dominated by hermaphrodites (XX), with rare presence of males (XO) in each population (Hodgkin, 2002).

Utilizing animal models in host-pathogen interaction studies has a distinct advantage compared to in vitro studies, as animal models can mimic cellular complexities that occur in humans more accurately (Graves et al., 2012). Using animals as hosts for studying pathogen interactions does have its limitations; but these models for host-pathogen studies is practical and important for better extrapolation of study results to the human condition. A variety of animals have been used as models for host-pathogen interaction studies, including primates, pigs, ferrets, cats, dogs and mice  (Lee, 1998). C. elegans has also been used widely as a model for host-pathogen interaction studies to investigate the effects of infection and colonization by various commensals or pathogens, be it bacterial or fungal. The nematode may activate its protective mechanism from infection either via avoidance behavior or via its innate immune response (when the pathogen could not be avoided). Table 1 summarizes infection source, pathogens, key features and experimental aspects of infections on C. elegans.

 

Table 1 Key features of infections in C. elegans (Marsh & May, 2012)

Source (type of infection) Pathogen Key feature (s) Molecular and Experimental aspects
Environment M. nematophilum Swelling of tail region (Dar); nonlethal Induces ERK MAPK response; infection limited to rectal area
D. coniospora Fungal infection: hyphae penetrate entire worm Induces NLP and CNC response genes; difficult to grow or control infectious dose
N. parisii Intracellular parasite Horizontal transfer of infection; unique immune response; cannot be cultured in vitro
Nodavirus Intestinal structure disrupted; life span unchanged Induces natural RNAi response; horizontally transmitted
Human (bacterial) P. aeruginosa Medium-dependent fast and slow killing, which are toxin and infection based, respectively Induces p38 MAPK response; killing mechanism is strain dependent
S. enterica Persistent bacterial infection Primarily an extracellular infection in C. elegans, unlike in mammals
S. marcescens Grossly distended intestine; 6-day survival Triggers inducible immune response; may be a natural host-pathogen interaction
E. coli Nonpathogenic food source; pathogenic strains exhibit fast and slow killing Results in a behavioral conditioning response; type III secretion system not required (unlike mammalian host)
S. aureus Intact bacteria overwhelm animal; not persistent until infection threshold reached bar-1 and egl-5 response is key; conservation of virulence factors between C. elegans and mammals
Human (fungal) C. albicans Persistent lethal infection Coinfection model particularly informative
C. neoformans Rapid infection, accumulation of yeast; not persistent Mechanism of pathogenesis unclear; does not disseminate in C. elegans (unlike mammalian host)

 

Unique characteristics of C. elegans which eases its utilization as an animal model includes ease in handling, a transparent body, its short lifespan (Rosa et al., n.d.) and lack of ethical concerns. In addition, C. elegans consumes bacteria (Escheria coli OP50) as its source of food (Legu et al., 2020), making it an easy model to be infected with microorganisms or pathogens that are being investigated.

C. elegans has been used widely as a model for methicillin-resistant Staphylococcus aureus (MRSA) infections (Wu et al., 2009), (Kong et al., 2014), (Day et al., 2012), (Son et al., 2016), (Peterson & Pukkila-Worley, 2018). In UKM Medical Molecular Biology (UMBI), we are equipped with a dedicated laboratory and conducive instruments required to handle C. elegans for host-pathogen interaction studies. We have conducted studies on the nematode infected with MRSA and tested its versatility in detecting sepsis (Tan et al., 2019; Tee et al., 2019). In Tan et al., (2019), the nematode was used as a model to investigate virulence of vancomycin-intermediate S. aureus (VISA) strains compared to vancomycin-susceptible S. aureus (VSSA) infections. C. elegans infected with VISA strains were found to have a shorter life span compared to nematodes infected with VSSA. In Tee et al. (2019), a C. elegans Sepsis Detection Assay (CESDA) was established, where the assay was able to identify sepsis and bacterial infection cases with good sensitivity and specificity using urine samples of patients admitted to the Department of Emergency Medicine (ED), Hospital Canselor Tuanku Mukhriz, Universiti Kebangsaan Malaysia (UKM).

In summary, C. elegans is a versatile model organism for host-pathogen interaction studies; with the development of various OMICS platforms, the nematode’s potential as a tool to better understand infectomics should be further explored.

 

References

Corsi, A. K., Wightman, B., & Editor, W. (2015). GENETICS | PRIMER A Transparent Window into Biology : A Primer on. 200(2446), 387–407. https://doi.org/10.1534/genetics.115.176099

Day, S. R., Moore, C. M., Kundzins, J. R., & Sifri, C. D. (2012). Community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus virulence toward Caenorhabditis elegans compared. Virulence, 3(7). https://doi.org/10.4161/viru.22120

Graves, D. T., Kang, J., Andriankaja, O., Wada, K., & Rossa Jr, C. (2012). Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis. Front Oral Biol, 15, 117–132. https://doi.org/10.1159/000329675.Animal

Hodgkin, J. (2002). Exploring the Envelope : Systematic Alteration in the Sex-Determination System of the Nematode Caenorhabditis elegans.

Kong, C., Yehye, Wageeh A, ABd Rahman, N., Tan, M.-W., & Nathan, S. (2014). Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model. BMC Complementary & Alternative Medicine, 14(4). https://doi.org/10.1063/1.4895251

Lee, A. (1998). Animal models for host-pathogen interaction studies. British Medical Bulletin, 54(1), 163–173. https://doi.org/10.1093/oxfordjournals.bmb.a011666

Legu, M., Id, J. U., Id, P. B., & Id, A. C. (2020). PLOS BIOLOGY Bacterially produced metabolites protect C . elegans neurons from degeneration. https://doi.org/10.1371/journal.pbio.3000638

Marsh, E. K., & May, R. C. (2012). Caenorhabditis elegans, A model organism for investigating immunity. In Applied and Environmental Microbiology (Vol. 78, Issue 7, pp. 2075–2081). https://doi.org/10.1128/AEM.07486-11

Peterson, N. D., & Pukkila-Worley, R. (2018). Caenorhabditis elegans in high-throughput screens for anti-infective compounds. Current Opinion in Immunology, 54, 59–65. https://doi.org/10.1016/j.coi.2018.06.003

Rosa, G. Di, Brunetti, G., Scuto, M., Salinaro, A. T., Calabrese, E. J., Crea, R., Schmitz-linneweber, C., Calabrese, V., & Saul, N. (n.d.). Healthspan Enhancement by Olive Polyphenols in C . elegans Wild Type and Parkinson ’ s Models.

Son, S. J., Park, M. R., Ryu, S. D., Maburutse, B. E., Oh, N. S., Park, J., Oh, S., & Kim, Y. (2016). Short communication: In vivo screening platform for bacteriocins using Caenorhabditis elegans to control mastitis-causing pathogens. Journal of Dairy Science, 99(11), 8614–8621. https://doi.org/10.3168/jds.2016-11330

Tan, X., Neoh, H., Cui, L., Hiramatsu, K., & Jamal, R. (2019). Oxidative stress resistance and fitness-compensatory response in vancomycin-intermediate Staphylococcus aureus ( VISA ). 628(May), 623–628.

Tee, L. F., Tan, T. L., Neoh, H., & Jamal, R. (2019). Short Communication Rapid Detection of Sepsis using CESDA : the Caenorhabditis elegans Sepsis Detection Assay. August 2018, 0–2. https://doi.org/10.1590/0037-8682-0300-2018

Wu, K., Conly, J., Mcclure, J., Elsayed, S., Louie, T., & Zhang, K. (2009). Caenorhabditis elegans as a host model for community-associated methicillin-resistant Staphylococcus aureus. Journal of Compilation, 16(3), 245–254. https://doi.org/10.1111/j.1469-0691.2009.02765.x