This is an overview of C.elegans with a perspective of utilisation of AMPs present in C.elegans as Innate Immune Response. Thus, these AMPs of C.elegans could be novel antibiotics.
2. Contents
● What are they?
● What is their role in Healthcare system?
● Antimicrobial peptides (AMPs).
● AMPs in C.elegans.
● Conclusion.
3. What are they?
● C.elegans are unsegmented, transparent and bilaterally symmetrical
non-pathogenic species (roundworm) belongs to the phylum
“NEMATODA”.
● Length 0.8 - 1.2 mm.
● Lives in temperate soil environment.
● Feeds on bacteria.
● Two types of sex,
1. Hermaphrodites: Contains 2 ovaries, 2 oviducts, spermatheca and
single uterus. (Can produce both sperm & egg)
2. Males: Contains single lobed gonad and tail specialized for mating.
5. What are they?
Hermaphrodites ability: Either they can lay eggs and develop them externally
(or) They can fertilize the eggs inside by their own sperm.
6. Reason behind using in healthcare
● First multicellular organism to have its genome completely sequenced.
● Genes and signalling pathways are well conserved between C.elegans and
humans.
● One of simplest organism with a nervous system.
● Transparent body wall.
● Small & easy to grow.
● Can grow on agar filled petri dish.
● Can be stored by freezing with 15% glycerol at -80 C for 10 years. (35-40%
recovery after long term storage)
● Short life cycle (3 days to 2 weeks).
9. Role in Healthcare systems
● First research into molecular and developmental biology of C.elegans was
begun in 1974 by Sydney Brenner.
● Since then it has been used extensively as a model organism to study
molecular mechanisms, screening of drugs etc.
● High throughput screening of various drugs such as anti-cancers (Apoptosis
& Autophagy), anti-alzheimer's, anti-bacterials, antifungals, antivirals and
also toxicity testing.
● Extensive research is progressing till date to make use of its innate defence
mechanism of killing bacteria and fungi.
● This may lead to development of novel Antimicrobial peptides (AMPs)
10. Antimicrobial peptides (AMPs)
● Also called host defence peptides.
● Part of Innate Immune Response found among all classes of life.
● Could be potent and novel therapeutic agents.
● They are cationic or amphiphilic alpha-helical peptide molecules.
● The mechanism involved is binding with opposite charged bacterial cell
membrane leading to change in electrochemical potential, destroying cell
morphology which results in cell death.
13. AMPs of C.elegans
Caenopores:
● They are pore forming proteins that can kill bacterias.
● Predominantly expressed in the C.elegans intestine which can be modulated
by specific pathogenic bacteria.
● Act synergistically with other AMPs while exhibiting Innate Immune
Response.
● Exact mode of action is not fully understood.
14. AMPs of C.elegans
Lysozymes:
● Second well characterized AMP in C.elegans.
● Their expression in the intestine can be induced by some pathogens.
● Secreted into the intestinal lumen to directly act on microbes.
● Resistance towards some gram positive and gram negative bacterias is
shown.
15. AMPs of C.elegans
ABF peptides:
● Slightly similar to vertebrate defensins.
● ABF-2 has demonstrated broad spectrum antimicrobial activity on gram
negative bacteria.
● Even in absence of immune challenge, ABF-1, ABF-2 & ABF-3 are
constitutively expressed.
● ABF-1 & ABF-2 are mainly expressed in pharyngeal tissues, where ABF-1 &
ABF-3 were also found in intestine.
16. AMPs of C.elegans
NLP & CNC:
● Many bacterial and fungal pathogens attack Nematodes following an initial
attachment to the cuticle.
● Expressions of NLP & CNCs were triggered by a gram positive bacteria
“Mycobacterium Nematophilum” and fungal pathogen “D. coniospora”.
● Recombinant NLP-31 shown to have antifungal activity against D.
coniospora and human opportunistic fungal pathogen aspergillus fumigatus.
17.
18. Conclusion
All these years the C.elegans have been majorly used to screen variety of drug
compounds such as anti-alzheimer's, antibiotics, anticancer, antifungals etc. But,
the families of antimicrobial peptides present in C.elegans as innate immune
response can also be the potential candidates for the development of novel
antimicrobial agents.
19. References
1. Kong C, Eng SA, Lim MP, Nathan S. Beyond Traditional Antimicrobials: A
Caenorhabditis elegans Model for Discovery of Novel Anti-infectives. Front
Microbiol. 2016;7:1956.
2. Lei J, Sun L, Huang S, Zhu C, Li P, He J, Mackey V, Coy DH, He Q. The
antimicrobial peptides and their potential clinical applications. Am J Transl
Res. 2019;11(7):3919-3931.
3. Ewbank JJ, Olivier Zugasti. C. elegans: model host and tool for antimicrobial
drug discovery. Disease Models & Mechanisms. 2011;4:300-304.