Anti-infective Compounds Screening Service

Since the discovery of the first antibiotic in 1928, a mass of antibiotics has been extensively used to fight infectious diseases. However, bacterial pathogens developing antibiotic resistance has become a growing problem, followed by attenuated effectiveness of the antibiotics in eradicating diseases. Despite numerous efforts made to tackle the spread of antimicrobial resistance, bacteria continue to exhibit reduced susceptibility toward antibiotics over time and the development of identification and production of new antibiotics has been slow. Therefore, new paradigms or discovering novel antibiotics for infections with multi-drug resistant pathogens are urgently needed to prevent the detrimental effects of the diseases. The nematode C. elegans, a live animal has been used in small molecule screening systems to identify anti-infective compounds with therapeutic potential. Due to the notable similarities between the nematode and higher vertebrates at molecular and cellular levels, it seems that C. elegans exhibit superior function over conventional antibiotics in the discovery of novel therapeutics for human infections. As a professional provider of C. elegans model services, we focus on C. elegans-based screens, which have been adopted to explore hundreds of thousands of compounds against a wide range of human bacterial and fungal pathogens. Here, we offer a high-throughput anti-infective compounds screen service using the advanced automatic equipment to meet our customers' research needs in this area.

Caenorhabditis elegans: a model for antimicrobial compounds discovery

C. elegans has been incorporated into small molecule screening, especially for novel anti-infective compounds. In nature, the animal lives in rotting plant material where it is exposed to bacterial and fungal pathogens. Previous stuantibiotics have beenvdies revealed that multiple human pathogens also infect C. elegans. For anti-infective compounds, the typical identification is by determining the influence of agents on the growth or killing of a pathogen. Notably, the incorporation of a live animal into the screening system can potentially identify the anti-infective compounds with new mechanisms of action that may have been missed in traditional screens. The systems offer the ability to identify molecules that promote innate immune responses for host survival and compounds that interfere with bacterial virulence mechanisms. Moreover, given that the endpoint of these screens is a live animal, it also offers an in-assay counter-screen against toxic molecules.

Schematic diagram illustrating the possible outcomes of a Caenorhabditis elegans-based anti-infective screen. Schematic diagram illustrating the possible outcomes of a Caenorhabditis elegans-based anti-infective screen. (Kong, C., et al, 2016)

Advantages of C. elegans high-throughput screening for anti-infective compounds

  • C. elegans can be infected with many human disease-causing pathogens and show the clear phenotypic cues of infection
  • The characteristics of C. elegans (small size, short lifespan, ease of cultivation) make it possible for high-throughput screens
  • Ability to identify anti-infective compounds, such as immunostimulatory and anti-virulent compounds
  • Ability to explore new classes of antimicrobials that target the pathogen
  • Ability to simultaneously assess compound toxicity

Service offerings

  • Screening for immunostimulatory compounds

This is an emerging strategy for developing new anti-infective small molecules via selective modulation of the host's innate immunity. And these are two obvious advantages. Compounds that augment core defense pathways might potentially tackle a wide range of pathogens. Besides, the target of anti-infectives is the host, rather than the pathogens, which leads to less selection pressure on bacteria to develop resistance. Notably, the promise of using C. elegans to identify immunostimulatory compounds with broad-spectrum antimicrobial activity is demonstrated in previous studies. Here, we adopt a C. elegans transgenic, GFP-based immune reporter strain to conduct primary screens of large compound libraries for immunostimulatory molecules in our platform. However, it is worth noting that whether the immunostimulatory compounds identified using the nematodes having an anti-infective effect on humans is still to be observed.

  • Screening for anti-virulence compounds

This is an attractive strategy for developing new anti-infective compounds by disrupting the virulence factor expression of pathogens. The strategy exerts therapeutic effects through disarming pathogens in the host, and the combination with bactericidal antibiotics might greatly improve their efficacy. Apart from interfering with bacterial virulence factor expression, we also offer another strategy for a high-throughput screen for anti-virulence compounds. Since Biofilms (main components include exopolysaccharide and DNA) play a crucial role in bacterial pathogenesis, it is important to target this virulence determinant.

  • Screening for pathogen-targeting compounds

We also provide the service to identify anti-infective compounds through directly targeting problematic bacterial pathogens. Additionally, to complementing antibiotic discovery service, C. elegans-based pathogenesis assays are deployed to identify new antifungal therapies in our platform.

  • Workflow of anti-infective compounds screening service

Workflow of anti-infective compounds screening service

Creative Biogene is a dedicated provider of C. elegans model services. Since C. elegans is widely used in infectious diseases modeling, the nematode has emerged as an excellent model for anti-infective compounds discovery and development. Here we provide anti-infective compounds screening service, involving immunostimulatory compounds, anti-virulence compounds and pathogen-targeting compounds. We are dedicated to accelerating the speed to achieve customers' research goals with high-quality. If you are interested in our service, please feel free to contact us for more information.

References

  1. Peterson ND, Pukkila-Worley R. (2018) "Caenorhabditis elegans in high-throughput screens for anti-infective compounds." Curr Opin Immunol. 54:59-65.
  2. Kong, C., et al. (2016). "Beyond traditional antimicrobials: A Caenorhabditis elegans model for discovery of novel anti-infectives." Frontiers in microbiology, 7, 1956.

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