Abstract
The recent emergence of a multidrug-resistant yeast, Candida auris, has drawn attention to the closely related species from the Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of C. haemulonii 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 C. haemulonii and C. duobushaemulonii 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 C. haemulonii and C. duobushaemulonii in Colombia, Panama, and Venezuela linked to substitutions in ERG11 gene as well as amplification of this gene in C. haemulonii 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.
Highlights
Yeasts from Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna (Sipiczki and Tap, 2016) are often misidentified as Candida auris, especially in laboratories that do not have access to DNA sequencing and matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS) (Hou et al, 2016; Araúz et al, 2018)
Five isolates from Colombia (N = 2), Panama (N = 2), and the United States (N = 1) that were identified by MALDITOF as closely resembling C. duobushaemulonii, which the subsequent analysis confirmed as C. vulturna, were included (Table 1)
A different distribution of cases was observed in Latin America: 77% of C. haemulonii and 67% of C. duobushaemulonii from Latin American countries (Colombia, Panama, and Venezuela combined) were from blood, and the remaining isolates were from wounds and non-invasive sites
Summary
Yeasts from Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna (Sipiczki and Tap, 2016) are often misidentified as Candida auris, especially in laboratories that do not have access to DNA sequencing and matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS) (Hou et al, 2016; Araúz et al, 2018). Recent comparative genomic analysis identified the substantial amount of conservation and synteny among genomes of C. auris, C. haemulonii, C. duobushaemulonii, and C. pseudohaemulonii as well as similar expansions of the oligopeptide transporters and lipase gene families (Muñoz et al, 2018). These shared genomic features suggest similarities in ecology and physiology of these species and raise a possibility that they may start emerging as drug-resistant pathogens in human populations. C. pseudohaemulonii and C. duobushaemulonii were identified in 2006 and 2012, respectively, as the distinct lineages within C. haemulonii species complex based on the phylogenetic analysis of rDNA intragenic spacer region (ITS) (Cendejas-Bueno et al, 2012). The first isolate of this species was isolated from flowers in the Philippines, and later it was isolated as a cause of human candidemia (Sipiczki and Tap, 2016)
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