Metabolic Pathway-targeted Antimicrobial Therapy Development

From a science popularization perspective, metabolic pathway-targeted antimicrobial therapy is akin to a highly specialized attack on a microorganism's internal "factory." At Protheragen, we offer comprehensive preclinical metabolic pathway-targeted antimicrobial therapy development services to support the discovery and optimization of novel antimicrobials.

Overview of Metabolic Pathway-targeted Antimicrobial Therapy

Metabolic pathway-targeted antimicrobial therapy is an innovative strategy in combating infectious diseases, particularly those caused by antibiotic-resistant pathogens. Unlike traditional antibiotics that broadly inhibit bacterial growth or disrupt cell wall synthesis, this novel approach specifically targets essential biochemical pathways required for microbial survival and proliferation. By doing so, it enhances treatment efficacy while minimizing disruption to the host's microbiome, thereby reducing the risk of side effects and the development of resistance.

Fig.1 (a) Overview of biosynthesis, metabolism, and effect of (p)ppGpp in virulence, antibiotic resistance, and other cellular processes in bacteria. (b) Overview of the TCA pathway with the different metabolites and essential genes. (Elbediwi M., et al., 2024)

The core principle of metabolic pathway-targeted antimicrobial therapy is based on the understanding that microorganisms, like all living organisms, depend on a complex network of metabolic pathways to synthesize essential molecules, generate energy, and maintain cellular integrity. By identifying and targeting key enzymes or intermediates within these pathways, microbial metabolism can be disrupted, leading to cell death or growth inhibition. This targeted approach offers a more precise and effective alternative to conventional antibiotics, providing a promising solution in the ongoing battle against antibiotic-resistant infections.

Development of Metabolic Pathway-targeted Antimicrobial Therapy

The development of metabolic pathway-targeted antimicrobial therapies has gained significant momentum in recent years, driven by the urgent need for new treatments to combat antibiotic-resistant infections. Several promising candidates have emerged from preclinical and clinical studies, demonstrating efficacy against a range of bacterial pathogens.

One notable example is the development of inhibitors targeting bacterial fatty acid synthesis pathways. These inhibitors have shown potent activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and are currently undergoing clinical trials. Similarly, inhibitors of bacterial cell wall biosynthesis pathways, such as those targeting peptidoglycan synthesis, have also shown promise as potential antimicrobials.

Table 1. Representative drugs targeting metabolic pathways in the therapeutic of infectious diseases.

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

At Protheragen, we are dedicated to specializing in the preclinical development of metabolic pathway-targeted antimicrobial therapies. By harnessing our extensive expertise in molecular biology, pharmacology, and bioinformatics, we are able to drive forward innovative solutions to effectively combat infectious diseases. Our comprehensive suite of services is meticulously designed to support the entire preclinical development process, encompassing everything from target identification and validation through to preclinical testing.

Workflow of Metabolic Pathway-targeted Antimicrobial Therapy Development

Target Identification and Validation

The initial step involves the identification of potential metabolic targets through comprehensive genomic and metabolomic analyses. By comparing the metabolic pathways of pathogens with those of human cells, we can pinpoint unique vulnerabilities that can be exploited for therapeutic intervention. Once potential targets are identified, we employ a range of in vitro and in silico techniques to validate their essentiality for microbial survival.

Therapeutic Development

• Enzyme Inhibition: One of the most direct approaches in metabolic pathway-targeted therapy is the inhibition of specific enzymes that are critical for microbial survival.
• Nutrient Depletion: Another strategy involves targeting pathways responsible for the synthesis or uptake of essential nutrients required by the pathogen.
• Monoclonal Antibodies: Monoclonal antibodies offer a highly selective means of targeting specific metabolic pathways in pathogens. These antibodies can be engineered to bind to specific enzymes, transporters, or other metabolic components, effectively inhibiting their function.
• mRNA-based Therapies: mRNA-based therapies represent an emerging and innovative approach in metabolic pathway-targeted antimicrobial therapy. By modulating the expression of key metabolic genes, mRNA therapies can disrupt essential pathways in pathogens.

Preclinical Research

Protheragen offers a wide range of preclinical testing to assess safety and efficacy. This includes in vitro studies to evaluate antimicrobial activity against relevant pathogens, as well as in vivo studies in animal models to assess pharmacokinetics, pharmacodynamics, and toxicity. Protheragen's comprehensive preclinical testing capabilities ensure that our clients receive robust data to support the advancement of their therapeutic candidates into clinical trials.

By selectively targeting unique metabolic pathways in pathogens, this approach offers a more precise and effective means of combating infections while minimizing collateral damage to the host microbiome. Protheragen is at the forefront of this innovation, providing comprehensive preclinical development services to advance the next generation of antimicrobial therapies. If you are interested in our services, please feel free to contact us.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.