In immunocompromised individuals the risk of a fungal infection, though statistically minor, needs to be taken seriously. If the pathogen is not recognised in time the delay may prove fatal cllsociety.org/2021/07/chro...
Studies have found increased rates of invasive fungal infections (IFIs) in CLL patients treated with a BTK inhibitor (BTKi) compared with those not treated with a BTKi academic.oup.com/ofid/artic... and hematologyadvisor.com/news/...
A broader issue is the advent of multi-drug resistant strains in common fungal pathogens.
The global spread of multidrug-resistant pathogenic fungi presents a serious threat to human health, necessitating the discovery of antifungals with unique modes of action. However, conventional activity-based screening for previously undescribed antibiotics has been hampered by the high-frequency rediscovery of known compounds and the lack of new antifungal targets. Here we report the discovery of a polyene antifungal antibiotic, mandimycin, using a phylogeny-guided natural-product discovery platform. Mandimycin is biosynthesized by the mand gene cluster, has evolved in a distinct manner from known polyene macrolide antibiotics and is modified with three deoxy sugars. It has demonstrated potent and broad-spectrum fungicidal activity against a wide range of multidrug-resistant fungal pathogens in both in vitro and in vivo settings. In contrast to known polyene macrolide antibiotics that target ergosterol, mandimycin has a unique mode of action that involves targeting various phospholipids in fungal cell membranes, resulting in the release of essential ions from fungal cells. This unique ability to bind multiple targets gives it robust fungicidal activity as well as the capability to evade resistance. The identification of mandimycin using the phylogeny-guided natural-product discovery strategy represents an important advancement in uncovering antimicrobial compounds with distinct modes of action, which could be developed to combat multidrug-resistant fungal pathogens.
nature.com/articles/s41586-... (full article)
and
Scientists have unveiled mandimycin—a newly discovered antibiotic with unparalleled properties that may revolutionize multidrug-resistant (MDR) fungal infection treatment—according to a study in Nature. Unlike conventional antibiotics, mandimycin boasts a unique mode of action: targeting fungal cell membrane phospholipids, disrupting ion balance, and sidestepping resistance mechanisms. Its potent, broad-spectrum fungicidal effects mark a significant leap in combating hard-to-treat fungal infections, offering hope in the battle against resilient superbugs...
...Mandimycin represents a new frontier in antifungal therapy, blending potent efficacy with innovative action. With its potential to address rising fungal infections in immunocompromised patients and overcome antifungal resistance, mandimycin could transform global healthcare landscapes. This discovery not only highlights the unexplored potential of microbial biodiversity but also offers hope against the escalating threat of antifungal resistance.
insideprecisionmedicine.com...
Sometimes the results of scientific research justify state support.
Which Antibiotic?
fungal infections
