Introduction
In the recent decade, the emergence of drug resistance is the most important threat to human health. Although a lot of work is ongoing for drug discovery, still conventional screening strategies have failed to yield desired results in the field of drug discovery. Therefore, new paradigms are of prime importance for novel and new drug discoveries.
Conventional in vitro tests for screening and drug discovery require additional costly experiments to determine the toxicity associated with the compounds. Furthermore, drug interactions need to be evaluated when in-vitro models are used thereby increasing the time. Therefore, cost-effective, high throughput in-vivo experimental models need to be explored for drug discovery.
Background
Currently, for the drug discovery studies, the researchers focus more on the in-vivo bioassays compared to traditional in vitro methods. For in vivo studies, the utility of whole animals such as C. elegans, is gaining importance as screening tools. Crucial pathogenesis features of microbial infections are expressed in animal hosts. C. elegans is considered an in-vivo model as it shows prime importance for host-pathogen interactions well as novel antimicrobial drug screening studies.
The coherence in the cellular complexity, as well as the disease pathways conservation, is found between C. elegans and higher organisms is reported in previous researches. Further, cultivation simplicity, rapid expansion to produce a homogenous population, and reduced cost make them ideal as in vivo model organisms. Availability of entire C. elegans genome sequence for C. elegans along with the development of numerous functional genomic approaches. Biological and genetic features of human genes along with their putative orthologous genes are obtained from WormBase21 for the C. elegans, model organism databases thus facilitating the novel drug responses at the genetic and proteomic level.
Numerous studies have employed C. elegans as a model organism for novel drugs and compound screening against microbial diseases. In many cases, studies have proved that virulence factors linked to C. elegans killing are also vital for pathogenesis in mammals. This opens new avenues for the virulence-specific targeted development of novel therapies.
One promising approach is to determine the compounds that function against bacterial quorum sensing mechanisms. In a recent study, a powerful antagonist of quorum sensing was found to have a protective role in the C. elegans from bacterial killing. Thus, using C. elegans as a model organism validated the idea of blocking quorum sensing using compounds that can be potent as antimicrobial drugs. In another study, using C. elegans newer high-throughput screen of approx. 40,000 compounds and the identification of 28 novel antimicrobials were reported. Moreover, in most cases, the compounds in vivo effective dose as antimicrobial was significantly lower compared to in-vitro (MIC) for E. faecalis growth prevention.
Aims
This research aims to evaluate C. elegans as novel animal models to study new treatments and understand the mechanisms of action of the screening drugs and compounds. Further, the effects at the level of genetics and proteomics can be identified along with the toxicological data.
Methodology
- elegans as model organisms, novel compounds of therapeutic importance, worm sorter, automated microscopy, and image analysis. C. elegans-based HTS assays
Expected outcome
Using C. elegans as the experimental model will determine the functional characterization of novel drug targets by using the techniques of genomics.