Whole-genome sequencing of Candida haemulonii species complex from Brazil and the United States: Genetic diversity and antifungal susceptibility

• Published in: Medical mycology (Oxford) Vol. 61; no. 4
• Main Authors: de Barros Rodrigues, Dality Keffelen, Lockhart, Shawn R, Berkow, Elizabeth L, Gade, Lalitha, Bonfietti, Lucas Xavier, Mazo Fávero Gimenes, Viviane, Silva Ruiz, Luciana, Bronze Macioni, Milena, de Souza Carvalho Melhem, Marcia
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 03-04-2023
• Subjects: Animals; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Brazil - epidemiology; Candida; Candidemia - microbiology; Candidemia - veterinary; Drug Resistance, Fungal - genetics; Genetic Variation; Microbial Sensitivity Tests - veterinary; United States; Brazil; United States; echinocandins; sequence analysis; drug resistance; candidemia
• ISSN: 1369-3786; 1460-2709; 1460-2709
• DOI: 10.1093/mmy/myad030

Abstract
Candida haemulonii complex species can be multidrug-resistant and cause infections such as candidemia. This study determined the genetic relationship between isolates from Brazil and the United States through whole-genome sequencing and performed antifungal susceptibility testing to investigate drug resistance. Contrary to what is widely described, most isolates were susceptible to azoles. However, an atypical susceptibility profile was found in 50% of Candida pseudohaemulonii strains, including resistance to the three echinocandins. Isolates from both countries formed distinct clusters with wide genetic diversity. Isolates from three hospitals in Brazil were clonal and involved in candidemia cases, pointing to the importance of improving hospital infection control measures and molecular identification.
Lay Summary
Candida haemulonii complex species is worldwide distributed, and this study aimed to evaluate the resistance to antifungal drugs in cases from Brazil and the United States, and also compare their genetic relationships. A total of 50 strains were studied; most of them from Brazil were from cases of bloodstream infections, while the strains from the United States came from cases of wounds and may be associated with diabetic patients. The vast majority of strains were resistant to amphotericin B, one of the most effective drugs, and susceptible to fluconazole. In addition, 50% of C. pseudohaemulonii strains were resistant to echinocandins. The strains from Brazil and the United States had no genetic relationship and formed two distinct groups. In three Brazilian hospitals, strains were clonal, indicating an intra-hospital transmission. Our findings contribute to guiding therapy in bloodstream fungal infections caused by C. haemulonii species and alerting for nosocomial transmission of this yeast complex species.