Understanding the Emergence of Multidrug-Resistant Candida: Using Whole-Genome Sequencing to Describe the Population Structure of Candida haemulonii Species Complex

Abstract

The recent emergence of a multidrug-resistant yeast, <i>Candida auris</i>, has drawn attention to the closely related species from the <i>Candida haemulonii</i> complex that include <i>C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii</i>, and the recently identified <i>Candida vulturna</i>. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of <i>C. haemulonii</i> complex from different geographic areas in order to assess population structure and the extent of clonality among strains. Although most isolates of all four species were genetically distinct, we detected evidence of the in-hospital transmission of <i>C. haemulonii</i> and <i>C. duobushaemulonii</i> in one hospital in Panama, indicating that these species are also capable of causing outbreaks in healthcare settings. We also detected evidence of the rising azole resistance among isolates of <i>C. haemulonii</i> and <i>C. duobushaemulonii</i> in Colombia, Panama, and Venezuela linked to substitutions in <i>ERG11</i> gene as well as amplification of this gene in <i>C. haemulonii</i> in isolates in Colombia suggesting the presence of evolutionary pressure for developing azole resistance in this region. Our results demonstrate that these species need to be monitored as possible causes of outbreaks of invasive infection.