Candidiasis is a global problem that is getting worse every year. It is caused by the fungus Candida albicans, which belongs to the genus Candida. Candida albicans is a fungal infection detectable in the mouth, intestines, and vaginal area. In healthy people, Candida infections are rarely dangerous. If the patient’s immune system is compromised, the infection can spread to other body parts, such as the blood, heart, and brain in rare situations. There are a lot of people who are asymptomatic carriers of the Candida fungus and have no symptoms or just have an infection of the skin which is itchy and can be easily treated. However, the Candida fungus, if it develops a systemic infection, can be difficult to cure properly. It continues to resist treatments and develops medication resistance.
A new groundbreaking approach for the development of new drugs targeted at effectively treating C. Albicans has emerged due to a study conducted by a group of international researchers. The structure of the fungal ribosome was determined using single-particle cryogenic electron microscopy, according to the new study published in Science Advances.
Using single-particle cryogenic electron microscopy to determine fungal ribosome structure.
The ribosome compositions of fungi and humans are similar. The similarity could be because both species’ biological processes of protein creation from genes are comparable. Because no antifungal medications have targeted systemic protein synthesis, this commonality restricts the efficacy of pharmaceuticals in treating fungal infections. There has also been a rise in antifungal resistance among fungi, necessitating the development of new drugs. The novel research from Guskov and other contributors was built on this foundation. They set out to figure out the ribosome structure of the Candida albicans fungus to find novel therapeutic targets. The traditional method, involving using X-ray crystallography to determine ribosome structures from laboratory-grown crystals, is more time-consuming.
Microscopy was chosen, and single-particle cryogenic electron microscopy was used. They used an electron microscope to image a large number of particles at a very low temperature. These photos of particles taken from various angles were then merged to create an atomic-resolution structure.
The researchers were able to compare the architecture of fungal ribosomes to yeast and rabbit models using this method. There was a single mutation at the E-site, which is a critical place in protein production, based on structural comparisons. This mutation prevents inhibitors like the antifungal cycloheximide (CHX) from attaching to Candida Albicans fungal ribosomes. By lowering the size of the binding site, the mutation precludes effective inhibitor attachment, rendering inhibitors ineffective.
The study’s findings will help develop novel medications that can treat fungal infections selectively. The recognition of differences in the structures of the E-site in fungal and human ribosomes, as well as information about inhibitor binding discrepancies, makes this conceivable.
The researchers wanted to create inhibitors that could stop fungus ribosomes but not human ribosomes. This provides a foundation for developing targeted antifungal medicines. Because systemic candida infections are potentially lethal and remain drug-resistant, medicines targeting specific fungal ribosome structures can now be produced. This breakthrough in candida infection treatment research will benefit both clinicians and patients.
The study brings into light ribosomal structural differences between Candida albicans fungus and humans. New drugs can now be targeted at treating otherwise fatal systemic candidiasis.