Intro

       The rise of antibiotic resistance has become a critical global public health threat, significantly complicating the treatment of bacterial infections. Among the most concerning resistant pathogens are the ESKAPE group, which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These pathogens are notorious for their ability to evade antibiotic therapy through various resistance mechanisms, leading to increased morbidity, mortality, and healthcare burdens. Notably, K. pneumoniae, A. baumannii, and P. aeruginosa have been designated by the World Health Organization (WHO) as critical-priority Gram-negative bacteria due to their multidrug resistance and limited treatment options. The urgent need for novel therapeutic strategies to combat these pathogens has driven extensive research into alternative antibiotics and combination therapies.

Challenges in Developing Antibiotics for Gram-Negative Bacteria
       Developing new antibiotics against Gram-negative bacteria is exceptionally difficult due to their complex and highly efficient resistance mechanisms. Traditional drug discovery approaches often rely on testing large collections of clinical isolates. However, these isolates typically have poorly characterized resistance mechanisms and highly diverse genetic backgrounds. The presence of unknown factors affecting resistance makes it challenging to pinpoint which specific mechanism plays a dominant role in conferring drug resistance. This lack of precision complicates antibiotic development and limits the effectiveness of resistance-targeting strategies.

A Novel Approach: The Antibiotic Testing and Screening Platform
       To overcome these challenges, our company has developed a cutting-edge Antibiotic Testing and Screening Platform using genetic engineering technology. This platform comprises three major bacterial species (K. pneumoniae, A. baumannii, and P. aeruginosa) each represented by dozens to hundreds of genetically engineered strains. These strains carry well-defined resistance mechanisms, enabling precise evaluation of compound efficacy against specific resistance determinants.
       Furthermore, our platform is designed with a controlled and standardized strain background. All genetically engineered resistant strains are derived from the same parental strain, ensuring a uniform genetic foundation. This approach not only enhances the platform’s expandability, allowing the incorporation of new resistance mechanisms to keep pace with the evolving landscape of antimicrobial resistance, but also provides researchers with a highly controlled environment for comparative analysis. The genetic consistency across strains enables precise evaluation of how individual resistance mechanisms influence the antibacterial activity of specific compounds, thereby improving the reliability and accuracy of antibiotic efficacy assessments.

Key Advantages of This Platform
       This system provides multiple benefits for antibiotic research and development:

1.Precision in Compound Design: Enables the development of novel compounds that bypass or neutralize specific resistance mechanisms. Provides insight into structure-activity relationships (SAR) to enhance drug efficacy.

2.Optimization of Combination Therapies: Facilitates the exploration of synergistic antibiotic combinations, where two or more antibiotics work together to overcome resistance. Helps identify optimal dosing strategies to improve treatment outcomes.

3.Advancing Targeted Treatments: Allows for the tailored selection of antibiotics based on a pathogen’s known resistance mechanisms. Reduces unnecessary antibiotic use, thereby slowing the spread of antimicrobial resistance.
 


Impact on Antibiotic Development
       By integrating this systematic approach, the platform streamlines the drug development process, reduces costs, and increases the success rate of discovering effective antibiotics. More importantly, it plays a crucial role in global efforts to combat antimicrobial resistance (AMR) by facilitating the development of targeted, resistance-breaking therapies. This platform represents a pivotal advancement in antibiotic discovery, offering a powerful tool for researchers and pharmaceutical companies to develop next-generation treatments against drug-resistant Gram-negative pathogens.
Patented in the United States (2020) and Taiwan (2022)