HomeENGLISH MAGAZINEMolds fighting their nosocomial super-bug cousins: who's killing who

Molds fighting their nosocomial super-bug cousins: who’s killing who

Immunodeficiency is the condition where the capability of the immune system to fight against diseases has been compromised. Immunocompromised people have a higher chance of contacting diseases compared to people with healthy immune systems. Immunodeficiency usually occurs as a consequence of several factors, such as diseases like AIDS and diabetes, chemotherapy, and organ transplant. Recently, doctors have noted an increased trend in the occurrence of life-threatening fungal infections–also called mycoses–in immunocompromised patients. In such cases, treatment requires the use of some special compounds with antifungal properties. Unfortunately, antifungal drugs currently available are very limited. In 2006, japanese scientists discovered a compound called eushearilide, from mold Eupenicillium shearii. It was found to have antifungal and antiyeast properties, and could tackle several fungi that were known to cause infections in humans. A team of scientists from the Tokyo University of Science had previously explored the unique chemical structure and the method of synthesis of eushearilide.

Now, this research group, led by Prof. Isamu Shiina of the Tokyo University of Science–which also includes Takayuki Tonoi (Tokyo University of Science), Katsuhiko Kamei and Naruhiko Ishiwada (Medical Mycology Research Center, Chiba University) has used their previous findings to derive compounds from eushearilide that may have improved beneficial effects. This study is published in the journal Molecules. Their aim of the team was to look at the antibacterial effects on various fungi and bacteria of the new antibacterial lead compound 23-demethyleushearilide, shortened as usharelide, derived from eushearilide. For this, first, eushearilide had to be converted into usharelide through a set of reactions, involving the alteration of molecules attached at the 23rd carbon atom of eushearilide. The process needed the so-called Julia-Kocenski olefination. Once usharelide and its structural variations were derived, they were tested for their antibiotic properties, specifically against fungi and bacteria. The researchers found that these compounds had significant promising antibiotic properties.

In particular, two of the several variations of usharelide showed antimicrobial properties against Candida albicans, a fungus that is the instigator of yeast infections. Meanwhile, most of the variations showed antimicrobial properties against Cryptococcus neoformans, which causes lung infections, meningitis, and encephalitis, particularly in AIDS patients. This finding echoed the previous findings on the antifungal properties of eushearilide. However, what was even more interesting is that these usharelide variations also showed good antibacterial properties against several disease-causing bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA), which is known to be a particularly difficult bacterium to tackle due to its resistance to several antibiotics and causes potentially fatal infections, particularly in people with weak immune systems. These findings emphasize the unique status and importance of eushearilide and its derivative usharelide in the treatment of several fungal diseases in immunocompromised people.

More significantly, these findings also shed light on the possible antibacterial properties of these compounds, which have not been adequately explored in research before. Usharelide has the potential for application in the treatment for patients with fungal diseases such as candidiasis, and in the elimination of hospital-origin infections caused by MRSA and vancomycin-resistant enterococci. This study definitely promises to be a step in the right direction for treating recalcitrant infections in immunocompromised people caused by dangerously pathogenic bacteria, which were once thought to be unconquerable. Prof. Shiina stresses on the importance of further studies, stating: “Antibiotic properties of eushearilide derivatives are not only against various fungi but also against bacteria, especially important drug-resistant bacteria such as MRSA, vancomycin-resistant enterococci and some strains of Pseudomonas that cause lethal nosocomial infections. This is a novel finding that definitely warrants deeper research, given the urgent need for MRSA treatment options”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Tonoi T et al., Shiina I. Molecules. 2019 Sep 22; 24(19). 

Murata T et al. J Nat Prod. 2018 Nov 26; 81(11):2364-70.

Tonoi T et al., Shiina I. J Org Chem. 2018; 83(15):7886.

Tonoi T et al., Shiina I. J Antibiot (Tokyo). 2016; 69(9):697.

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica e salute sui siti web salutesicilia.com, medicomunicare.it e in lingua inglese sul sito www.medicomunicare.com
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