New work has shed light on the virulence factors of a dangerous, emerging fungi with multidrug resistance, and has also helped to identify a novel antifungal, SCY-078, which could potentially be used to save the lives of those infected by the organism.
Candida auris was first reported in 2008 after being isolated from a patient in a Japanese hospital. Since then, it’s become a widespread threat – the US, the UK, India, South Korea, Japan and Kuwait, to list a few countries, have all reported patients suffering from C. auris infections. The fungus, which is reported to carry an approximate mortality rate of 60%, often infects hospital patients, and shows a high incidence of multidrug resistance, often able to withstand the effects of fluconazole as well as other major antifungals. Due to this, treatment for those infected can be extremely difficult.
The study, which was published in Antimicrobial Agents and Chemotherapy on 21st February 2017, was carried out to unravel some of the mystery behind C. auris’ growth patterns and its virulence factors, the molecules the fungus produces to help it infect us. The research team also set out to assess how C. auris reacts when exposed to a series of 11 antifungals including SCY-078, an antifungal which can be orally administered and works by interfering with the process of cell wall synthesis.
This work is important as it marks the first investigation into C. auris in such a wide scale. While similar research has been conducted in the past, it has often only focussed on local strains of the fungus – in this study, several strains from across the world were used, including those isolated from patients in Japan, Germany, Korea and India.
While the strains of C. auris showed a variable level of resistance to the antifungals, SCY-078 was able to completely inhibit growth of the fungus at low concentrations. In addition, the drug was also able to change the structure of the fungal cells, distorting them and causing the cells to fuse to each other which prevented them from dividing.
SCY-078 also reduced the density of biofilms formed by C. auris, an important finding as its thought that one of the main ways the fungus is able to infect patients is by forming biofilms on catheter surfaces. Another reason this finding is significant is because a common trait of biofilms is that they often show drug resistance – the fact that SCY-078 can show an effect is a promising sign.
Work to gain information on how C. auris operates also gave some interesting results. The research team found for the first time that the fungal strains typically didn’t have the ability to germinate and form spores, and that when they were grown on silicone elastomer (to simulate catheter surfaces), the resulting biofilm was fairly thin – around half as thick as that of Candida albicans.
The production of the virulence factors proteinase and phospholipase, two enzymes which cause the breakdown of structures in our tissues to facilitate infection, wasn’t uniform, with only certain strains of C. auris producing either.
With these ‘weaknesses’ that C. auris possesses, it’s interesting that the fungus is able to spread and infect patients as well as it can. Perhaps, as the paper says, it could be that the ability of the organism to resist the action of multiple drugs comes at a cost of fitness.
In describing the threat of C. auris, Dr. Mahmoud Ghannoum of the research team said, “This emerging fungal species has started to infect patients globally, causing invasive infections that are associated with a high death rate.
It is multidrug resistant and some strains isolated from patients are resistant to all commercially available antifungal drugs. Multidrug resistance used to be reported for bacteria only, and now we must add fungi to that list.”
In providing us with more information about C. auris’ virulence factors and growth, this study has potentially helped us edge closer to discovering a mechanism that a novel antifungal could target in order to kill or inhibit the growth of the organism.
It also provided the first evidence that SCY-078, an antifungal with previously established efficacy against several other drug susceptible and resistant species of Candida, is also effective against C. auris.
As Dr. Ghannoum stated, “Understanding the virulence of C. auris and showing that the investigational drug (SCY-078) is effective may lead to the development of new medications to combat this emerging health threat.”