Disruption of Iron Homeostasis and Mitochondrial Metabolism Are Promising Targets to Inhibit Candida auris

Abstract

Over the last decade, Candida auris has emerged as a human pathogen around the world causing life-threatening infections with wide-spread antifungal drug resistance, including pandrug resistance in some cases. In this study, we addressed the mechanism of action of the antiparasitic drug pyrvinium pamoate against C. auris and show how metabolism could be inhibited to curb C. auris proliferation.

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug

“…Although the use of PP as an anthelminthic has dwindled over the years, since the early 2000s, interest in PP has surged due to its potential utilization to target other diseases-causing organisms at every level from viral [ 27 , 28 ] through bacterial [ 29 , 30 , 31 ], plasmodium [ 32 ], and fungi [ 33 , 34 , 35 ] to multicellular organisms [ 36 ] ( Figure 2 ). PP has also shown significant potential in multiple disease types for the ability to reduce toxicity, promote wound repair, and inhibit fibrotic tissue development [ 37 , 38 , 39 , 40 , 41 , 42 ].…”

Candida auris: Multidrug resistance and new treatment strategies

“…Simm et al [7] established that by triggering metabolic dysfunction through the use of pyrvinium pamoate it represses fungal proliferation and enhances drug susceptibility. The study shows that fungal pathogens need metabolic adaptability due to the lack of macro and micronutrients from the host.…”

“…The study shows that fungal pathogens need metabolic adaptability due to the lack of macro and micronutrients from the host. As a defense mechanism from the macrophages called nutritional immunity, the host is able to sequester iron in order to reduce its availability to the fungal pathogens impeding its replication [7]. This adaptability triggered by encoded genes has been allowing access to the host's iron via siderophores transporters.…”

“…By allowing nutritional deprivation on C. auris, the synergism with antifungal conventional therapy enhances action against this emergent yeast, except fluconazole [7].…”

“…Diabetic and organ transplantation patients are also on the verge of the risk [5]. The considerable challenge of this infection is its multidrug resistance ability alarmingly being reported as resistant to at least two of the three classes of current antifungal therapy, such as azoles, echinocandins, and polyenes, at an extremely high rate reaching up to 93% [5,7]. As an alternative, echinocandins are now becoming the first choice in treating this infection.…”