Phage-encoded lysins are an attractive class of antibacterial drugs that offer new perspectives on tackling drug resistance. In particular, custom engineering of lysins provides a powerful platform for creating variants targeting potential bacterial pathogens. At Creative Biolabs, we present a high-throughput hit-lead development platform for screening natural or engineered phage lysins against numerous bacteria and bacterial infections. We constructed many lysin variants. With an advanced platform, we have successfully identified lead variants with high antimicrobial activity.
In recent years, the recombination of lysin module domains has emerged as an attractive approach. Notably, the reorganization of the cell wall binding domain (CBD) and enzymatically active domain (EAD) plays an increasingly significant role in altering specificity or improving the stability, activity, and solubility of lysins. Each variant consists of a combination of at least one outer membrane permeabilizing peptide (OMP), a linker, a CBD, and an EAD. Each ingredient is closely linked to antibacterial activity. Therefore, a reliable discovery platform is required to confirm the optimal combination for a specific species. Traditionally, HTS is a drug discovery process that allows for automated testing of large numbers of compounds for a specific biological target. Currently, this strategy plays a crucial role in lysin screening.
Fig.1 An iterative three-step approach to design, build, test, and analyze engineered lysins. (Gerstmans, 2020)
The modular composition of lysins is a unique feature that enables the optimization of antibacterial and pharmacological properties through lysin candidate engineering. Advanced technologies that allow for the rapid construction of large modular lysin libraries based on prefabricated building blocks are available at Creative Biolabs. Our scientists performed high-throughput construction and screening of multiple combinatorial lysin libraries with different configurations for specific bacteria. Our unique lysin HTS technology offers new prospects for the discovery of engineered lysins.
The screening method is universal in nature and can potentially be translated to any bacterial target. Additionally, every possible configuration can be explored. Notably, by extension, our platform can be used to create DNA libraries encoding any modular protein variant, providing many opportunities for the protein engineering toolbox. Our dedicated scientists focus on developing a rational target organism screening protocol based on your project needs.
HTS is a complex process that requires strong biological knowledge and advanced platforms. At Creative Biolabs, our expert scientists have sufficient knowledge of HTS. We specialize in providing comprehensive phage lysin HTS services to facilitate the progress of phage lysin-based therapy development for our global clients. If you are interested in our technologies and services, please contact us for more information.
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