A deadly pathogenic fungus known as Candida auris has been described as one of the most concerning emerging infections.

It is a multidrug-resistant organism that has caused outbreaks in healthcare settings worldwide, and which may be difficult to identify, treat, and control. Although scientists have known about the fungus for less than a decade, it has spread to over 30 countries and is already resistant to all major classes of antifungal drugs.

What is Candida auris?

Candida auris is an emerging fungal pathogen responsible for invasive infections that can be life-threatening, especially in people with impaired immune systems.

It was first identified in Japan in 2009, but it has since been reported in many other countries, including the United States, the United Kingdom, India, South Africa, and Venezuela. It has been isolated from various clinical specimens, including blood, urine, respiratory secretions, wounds, and other anatomical sites.

Why is Candida auris a cause for concern?

Candida auris is a cause for concern because it is multidrug-resistant, meaning that it is resistant to several classes of antifungal drugs.

This makes it difficult to treat, especially in patients who are already immunocompromised or have other underlying health conditions. In addition, it has been associated with high mortality rates, ranging from 30% to 60% depending on the geographic location and patient population.

How does Candida auris develop drug resistance?

Drug resistance in Candida auris is a complex phenomenon that involves several genetic and biochemical mechanisms.

One of the main mechanisms is the overexpression of efflux pumps, which are membrane transporters that pump antifungal drugs out of the cell and reduce their intracellular concentration. Another mechanism is the alteration of drug targets, such as the enzymes that are inhibited by azole drugs. This can lead to a decrease in drug binding affinity and efficacy.

Finally, some Candida auris isolates may acquire resistance genes through horizontal gene transfer, which can confer resistance to multiple drugs.

How did scientists discover the mechanisms of drug resistance in Candida auris?

Scientists at the Broad Institute of MIT and Harvard, in collaboration with researchers from the University of Texas and Duke University, recently investigated the genetic and biochemical mechanisms underlying the drug resistance of Candida auris.

They used a combination of genomics, transcriptomics, proteomics, and metabolomics to profile the expression and activity of genes, proteins, and metabolites in drug-resistant and drug-sensitive isolates of Candida auris.

What did the researchers find?

The researchers found that Candida auris develops drug resistance through a complex network of genetic and biochemical interactions.

One of the key findings was the overexpression of a gene called CDR1, which encodes an efflux pump that pumps antifungal drugs out of the cell. They also found that the overexpression of CDR1 is regulated by a transcription factor called Mrr1, which binds to the promoter of CDR1 and activates its expression.

In addition, the researchers identified several other genes and proteins that are involved in drug resistance, including genes that encode enzymes involved in steroid biosynthesis, genes that are involved in stress response and DNA repair, and proteins that are involved in protein folding and degradation. They also found that Candida auris can produce a variety of metabolites, some of which may play a role in drug resistance.

What are the implications of the study?

The study has several important implications for the diagnosis, treatment, and control of Candida auris infections.

First, it provides a better understanding of the genetic and biochemical mechanisms underlying drug resistance in the fungus, which can inform the development of new antifungal drugs that target these mechanisms.

Second, it highlights the importance of accurate and timely identification of Candida auris infections, as well as infection control measures, to prevent the spread of multidrug-resistant strains.

Third, it underscores the need for continued surveillance and monitoring of Candida auris, both in healthcare settings and in the environment, to detect emerging strains and outbreaks.

Conclusion

Candida auris is a major health concern due to its multidrug-resistant nature and high mortality rates.

The recent study by scientists at the Broad Institute of MIT and Harvard sheds light on the genetic and biochemical mechanisms underlying drug resistance in the fungus. This knowledge can inform the development of new antifungal drugs and help improve the diagnosis, treatment, and control of Candida auris infections.