Strategies to combat the multidrug-resistant microorganism: Candida auris, new emerging fungal monster
By: Dr. Bahgat Fayed
Post-doctoral Research Associate, Infectious disease and anti-infective therapy research group, Sharjah Institute of Medical Research, University of Sharjah
Date/Time: Wednesday, February 24, 2021 at 2:00PM
Venue: MS Teams: Click here to join the meeting
Candida auris is an emerging multi-drug-resistant yeast that was first isolated from the external ear canal in Japan, 2009. C. auris has been considered as a global threat since it has been reported in more than 39 countries. Resistance to the available antifungals, and the lack of standard identification technique are most likely the underlying causes of high mortality rate due to C. auris infection. A case study in UAE, indicated that C. auris has developed a significant resistance against caspofungin, first line of treatment, in-patient mis-diagnosed and mis-treated. A patient suffered from Candida infection that was misdiagnosed initially as C. haemulonii and received caspofungin following the identification of its minimum inhibitory concentration (MIC). However, the patient did not respond to the treatment and the MICs of caspofungin and other antifungal drugs including amphotericin and voriconazole were significantly increased. Consequently, the clinical isolate was re-diagnosed and confirmed as C. auris. Eventually, after 11 weeks of treatment with caspofungin, the MIC increased up to ~16 times. Treatment was then switched to amphotericin B, however, the patient died few days later. Following this case, we tried to decipher the reason for increasing the MIC of caspofungin due to the repeated exposure of C. auris to caspofungin. Our data showed that C. auris exposed to caspofungin exhibited an elevated MIC50, slower growth, elevated chitin content and overexpression of caspofungin target gene (FKS1) and chitin synthase genes (CHS1 and CHS2) with no effect on the efflux pump gene CDR1. Interestingly, caspofungin exposure induces cell-cell adherence to C. auris accompanied with overexpression of agglutinin-like sequence protein-encoding gene ALS5 and enhancement of biofilm formation. Our results also confirmed that repeated exposure to caspofungin not only induce C. auris resistance to caspofungin but also resistance to fluconazole. Collectively, mis-use of antifungals including the current first-line of treatment can lead to acquired cross resistance, which is difficult to be treated.
Bahgat Fayed is a Postdoctoral Research Associate since December 2019 at Research Institute of Medical & Health Sciences (RIMHS). He is a member of the "Infectious disease and anti-infective therapy research group" led by Dr. Sameh Soliman. He obtained his PhD in biology from University of York (UK) in association with Cairo University. He has received the prestigious Fulbright award in 2018 to carry his research at UCLA, USA for 1 year. His research interest mainly focus on combating multidrug resistance microorganism by either discovery of novel antibiotics or deciphering the microbial resistance mechanisms. He co-authored 3 research articles and submitted 1 patent since he joined University of Sharjah.