Antibiotic Adjuvants Development
The number of multi-drug resistant superbugs continues to increase dramatically and has spread globally. We urgently need alternatives to fight drug-resistant bacteria. One such approach is the development of small molecule antibiotic adjuvants. This approach works by hindering the bacterial resistance mechanism and making the bacteria sensitive to antibiotics.
On the basis of combating various resistance mechanisms, Ace Therapeutics offers several services for developing potential antibiotic adjuvants, including adjuvants that inhibit the degradation of antibiotics by β-lactamases, adjuvants that modulate the permeability of bacterial extracellular membranes, and adjuvants that increase the intracellular concentration of antibiotics by inhibiting efflux.
What Are Antibiotic Adjuvants?
The antibiotic adjuvant approach involves combining an antibiotic with a non-bactericidal compound to increase the activity of the antibiotic by blocking the resistance mechanism. These compounds, which do not have bactericidal activity, are called antibiotic adjuvants. There is a potential advantage to developing antibiotic adjuvants. Using them to treat bacteria may not accelerate the development of resistance too quickly. Antibiotic resistance occurs through three main mechanisms, including inactivation of the antibiotic, increased antibiotic efflux, or decreased antibiotic uptake. Therefore, proteins involved in these resistance mechanisms are attractive potential targets for the development of adjuvants.
Fig. 1 Schematic representation of the main bacterial mechanisms of antibiotic resistance. (González-Bello C, 2017)
Various Antibiotic Adjuvants Development Services
- The most successful adjuvants in clinical practice today are β-lactamase inhibitors and have proven their robustness and value in past treatments. Ace Therapeutics offers development services for antibiotic adjuvant β-lactamase inhibitors, which are effective in targeting resistant bacteria by directly targeting resistance or otherwise enhancing the activity of β-lactam containing antibiotics.
- Some emerging resistant strains often have outer membrane modifications that limit the entry of small molecules such as antibiotics. To better improve antibiotic uptake, we provide research services in the development of novel antibiotics designing and using outer membrane permeabilizer compounds that can facilitate antibiotic diffusion and increase their intracellular concentration.
- Active efflux is a mechanism by which bacteria develop resistance to a specific antibiotic or multiple antibiotics. In this context, the use of efflux pump inhibitors (EPIs) appears to be a promising strategy for overcoming multidrug resistance. We provide solutions for restoring bacterial susceptibility through efflux pump inhibitor molecules designed to improve the entry of antibiotics into bacterial cells and prevent their excretion.
We Offer Target Strategies
We use proteins involved in bacterial resistance mechanisms as attractive potential targets for the development of antibiotic adjuvants. In addition, signaling and regulatory pathways that control the activation of these resistance mechanisms are also referenced as potential ancillary targets.
- Inhibition of antibiotic-modified enzymes
- Inhibition of the altered target of antibiotics
- Inhibition of antibiotic efflux
- Enhancement of antibiotic uptake
- Interfering with the signaling system that turns on the drug resistance mechanism of bacteria
- Targeting non-essential steps in cell wall synthesis
References
- González-Bello C. Antibiotic adjuvants–A strategy to unlock bacterial resistance to antibiotics. Bioorganic & medicinal chemistry letters, 2017, 27(18): 4221-4228.
- Melander R.J and Melander C. Antibiotic Adjuvants. In: Antibacterials. Topics in Medicinal Chemistry, 2017, 25.