Tuesday, August 23, 2016

mSphere: Comparative Pathogenicity of UK Isolates of the Emerging Candida auris


Almost two months ago, in PHE On The Emergence Of Candida auris In The UK, we looked at the first UK detections of  C. auris - an emerging fungal pathogen first isolated (roughly 7 years ago) from the discharge from a Japanese patient's external ear (hence the name `auris').

This UK report came on the heels of a clinical alert to U.S. Healthcare facilities from the CDC about the Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris. 

In recent years there have been a small, but growing, number of cases (and hospital clusters) reported internationally, generally involving bloodstream infections, wound infections or otitis.

Unlike most systemic Candida infections, which usually arise when a previously colonized person is weakened from illness or infirmity, this strain appears to have a propensity for nosocomial transmission.

Complicating matters:
  1. C. auris infections have a high fatality rate
  2. The strain appears to be resistant to multiple classes of anti-fungals 
  3. And it can be difficult for labs to differentiate between Candida strains

ASM's open access journal mSphere has published the first analysis of the recently announced UK isolates, and their comparative pathogenicity to other fungal strains using the Galleria mellonella infection model

G. melonella  - the greater wax moth or honeycomb moth - may seem an odd choice for a infection model, but it has a number of practical advantages over mammalian models, and has been used to study both fungal and bacterial pathogens.

A backgrounder on their use can be found in The insect Galleria mellonella as a powerful infection model to investigate bacterial pathogenesis.

This study found that C. auris isolates collected in the UK displayed varying growth characteristics in vitro, and that the most virulent isolates exhibited pathogenicity comparable to that of C. albicans - considered to be the most pathogenic strain - in the G. melonella model. 

Follow the link to read the full report:

Andrew M. Borman, Adrien Szekely, Elizabeth M. Johnson

Aaron P. Mitchell, Editor

Candida auris, first described in 2009, has since emerged as an important, multidrug-resistant, nosocomial agent of candidemia, with large outbreaks reported worldwide and high mortality rates associated with therapeutic failure. The current study employed C. auris isolates from a variety of centers in the United Kingdom to evaluate the pathogenicity of this emerging pathogen compared to that of other common pathogenic yeast species in the invertebrate Galleria mellonella infection model. 

We showed that C. auris isolates differ in their growth characteristics in vitro, with a proportion of isolates failing to release daughter cells after budding, resulting in the formation of large aggregates of cells that cannot be physically disrupted. 

Our results also demonstrate strain-specific differences in the behavior of C. auris in G. mellonella, with the aggregate-forming isolates exhibiting significantly less pathogenicity than their nonaggregating counterparts.
Importantly, the nonaggregating isolates exhibited pathogenicity comparable to that of C. albicans, which is currently accepted as the most pathogenic member of the genus, despite the fact that C. auris isolates do not produce hyphae and produce only rudimentary pseudohyphae either in vitro or in G. mellonella.

IMPORTANCE The incidence of invasive candidiasis, which includes candidemia and deep tissue infections, continues to rise and is associated with considerable mortality rates. Candida albicans remains the most common cause of invasive candidiasis, although the prevalence of non-albicans species has increased over recent years. 

Since its first description in 2009, Candida auris has emerged as a serious nosocomial health risk, with widespread outbreaks in numerous hospitals worldwide. However, despite receiving considerable attention, little is known concerning the pathogenicity of this emerging fungal pathogen. 

Here, using the Galleria mellonella insect systemic infection model, we show strain-specific differences in the virulence of C. auris, with the most virulent isolates exhibiting pathogenicity comparable to that of C. albicans, which is currently accepted as the most pathogenic member of the genus.
 (continue . . . )