Creative Biolabs has always been devoted to assisting our worldwide clients to develop next generation of antifungal therapies. Currently, we proudly present our exclusive service to investigate the mechanism of action of your compound concentrating on interference with the fungal cell membrane.
The emerging technology of whole-genome sequencing enables exploration of therapeutic targets against pathogenic fungi to a previously unprecedented extent. However, no matter in the past or present, fungal cell membrane has always been a predominant target, directly or indirectly. Like all eukaryotes, the fungal cell membrane is organized as a phospholipid bilayer with multiple transmembrane proteins. In fungi, the primary membrane sterol is ergosterol, which is unique in contrast to animals. There located various functional proteins, such as enzymes, proton pumps, and ion transporters, on the membrane surface, essential for cell permeability, signal transduction, and cell wall morphogenesis.
Figure 1. Structure of fungal membrane. (Guimarães et al. 2014)
Given the pivotal role of the plasma membrane in fungal structure and physiological function, therapeutics targeting fungal cell membrane has long been considered as a hotspot. Based on comprehensive knowledge of fungal plasma membrane and unparalleled technique platform, Creative Biolabs has established an integrated service to uncover the MOA of your test compound focusing on the fungal cell membrane.
In general, mechanisms of interfering with fungal plasma membrane including but not limit to following aspects:
Interference with Fungal Sterol Synthesis
Substances that inhibit ergosterol biosynthesis may impact the membrane permeability and fluidity as well as membrane-associated enzyme activity, thereby resulting in the elimination of pathogenic fungi. Many antifungal agents take effects in this manner, such as azoles, allylamines, and phenylmorpholines. Creative Biolabs employs multiple assays to evaluate ergosterol expression, and analyze entire pathways to decide which part is altered in response to test chemicals.
Interference with Cell Permeability
By interacting with essential membrane components, certain chemicals can alter membrane permeability and cause eventual death. One typical representative is polyene, particularly amphotericin B, which can bind to ergosterol, thereby disturbing membrane permeability and causing fatal leakage. Permeability changes and membrane integrity damage will be determined by specialized assays, and the application of interaction mapping enables validation of potential interaction mode.
Interference with Sphingolipid Synthesis
Sphingolipid is another indispensable component of the fungal plasma membrane, implying a potential antifungal target. Inhibitions of serine palmitoyltransferase, ceramide synthase, inositol phosphoceramide synthase are all promising mechanisms of antifungal therapies. In similarity to ergosterol, we have developed a comprehensive assessing protocol for sphingolipid biosynthesis, including most key factors involved in this pathway.
This exclusive service of Creative Biolabs can offer an accurate and unbiased perspective of the mechanism of action regarding interference with the fungal membrane, paving the way for identifying and characterizing attractive antifungal drugs of future.
For more detailed information, please feel free to contact us or directly sent us an inquiry.
Reference
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