Friday, 19 August 2016 11:56

Fungus Causing Fatal Infections in Hospitalized Patients Has Unique Growth Patterns

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Published in mBiosphere

By: Karen Bluis

One of the important tasks of Public Health England’s Mycology Reference Laboratory is to identify any newly emerging fungal pathogens that could become a public health risk. In recent months, the lab had tracked several clusters of Candida auris infections in British hospitals. The multidrug-resistant C. auris yeast, first described in 2009 after being isolated from external ear discharge of a patient in Japan, has caused bloodstream infections, wound infections and ear infections (including some fatal infections in hospitalized patients) in South Korea, India, South Africa and Kuwait, according to the Centers for Disease Control and Prevention. The organism also has been identified in Colombia, Venezuela and Pakistan.

“Reports from Asia suggest it has been associated with mortality rates of 30-60%, with worse outcomes reported in patients who have underlying severe illness,” says Andrew M. Borman, PhD, principal clinical scientist and deputy director of the lab. “Treatment is complicated by this organism’s invariable resistance to some classes of antifungal agents, as well as its propensity to develop resistance to other classes of drugs during therapy.”

In addition, C. auris is closely related to several other Candida species and shares morphological and biochemical characteristics, Borman says, “so several of the traditional identification methods confuse it with these other Candida species.”

To better understand C. auris’ biology, Borman and colleagues compared its pathogenicity against other common Candida species. Their findings, published in mSphere this week, demonstrate that the organism has at least two different growth forms and some of its strains are as capable of causing disease as C. albicans, which is currently accepted as the most pathogenic member of the genus.

“This organism has the propensity to persist and spread within the hospital environment, with large numbers of patients becoming colonized,” Borman says. “We need to understand why C. auris has only become a worldwide issue over the last few years, why it has ‘emerged’ so rapidly, and where it is found outside of the human population.”

The investigators compared 12 C. auris isolates taken from patients treated at six National Health Service hospitals in England with isolates from other disease-causing Candida species. To do so, they injected young wax moth larvae (Galleria mellonella, an insect model used to study human infection) with the assorted Candida strains.

Screen Shot 2016-08-20 at 4.50.11 PM
Non-aggregating C. auris (left) and aggregating C. auris (right)

Normally, yeast copies itself and divides during growth. But the C. auris isolates differed in their growth characteristics, with a proportion failing to release daughter cells after budding, resulting in the formation of large aggregates of cells that could not be physically disrupted (see image, left). The investigators also found strain-specific differences in the behavior of C. auris, with the aggregate-forming isolates exhibiting significantly less pathogenicity than their non-aggregating counterparts. The non-aggregating isolates exhibited pathogenicity comparable to C. albicans.

Screen Shot 2016-08-20 at 4.45.43 PM
C. auris forms hyphae (left) and yeast cells (right). Scale bar, 10 um

“Despite receiving considerable attention since its first description, little is known concerning the pathogenicity of this organism,” said study coauthor Elizabeth Johnson, PhD, director of the National Mycology Reference Laboratory. “We were surprised to find two very different growth forms of C. auris depending on the strain. We were also surprised by the virulence of this species because in most other types of Candida, the ability to cause disease relates to the organism’s ability to form hyphae (fine, branching tube-like structures) (see figure, right). C. auris is not able to form these hyphae in the lab or in the insect infection model, so we would have predicted reduced pathogenicity.”

Continuing studies will investigate whether the aggregate-forming behavior affects the organism’s susceptibility to antifungal agents, Johnson said: “Although these strains appear to be less pathogenic in our model, our latest results have shown that they also appear to be less susceptible to antifungal agents so treatment of infections with these strains may still be compromised. The major challenge facing researchers is to fully understand what makes this particular species behave so differently.”

Photo credits: C. aurus images from mSphereJ report

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