Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection

@article{daneshnia2026outbreaks,
  title = {{Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection}},
  author = {Farnaz Daneshnia and Deepika Gunasekaran and Sean Bergin and Lisa Lombardi and Austin M. Perry and Liuyang Cai and Louise A. Walker and Tibor Nemeth and Süleyha Hilmioglu-Polat and Letal I. Salzberg and Arefeh Ebadati and Tobias Köhler and Gabriel Braune and João N. de Almeida and Giuseppina Caggiano and Julianne V. Kus and Pegah Mosharaf Ghahfarokhy and Julieta Munoz and Daniel J. Floyd and Diego Fuentes-Palacios and Samuel M. Gonçalves and Relber A. Gonçales and Mostafa Salehi and Jigar V. Desai and Agostinho Carvalho and Shenglin Mei and Carol A. Munro and Alex Hopke and Toni Gabaldón and Attila Gacser and Oliver Kurzai and Geraldine Butler and David S. Perlin and Wenjie Fang and Clarissa J. Nobile and Michael K. Mansour and Amir Arastehfar},
  journal = {PLOS Biology},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pbio.3003973},
  url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003973},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection
AU  - Farnaz Daneshnia
AU  - Deepika Gunasekaran
AU  - Sean Bergin
AU  - Lisa Lombardi
AU  - Austin M. Perry
AU  - Liuyang Cai
AU  - Louise A. Walker
AU  - Tibor Nemeth
AU  - Süleyha Hilmioglu-Polat
AU  - Letal I. Salzberg
AU  - Arefeh Ebadati
AU  - Tobias Köhler
AU  - Gabriel Braune
AU  - João N. de Almeida
AU  - Giuseppina Caggiano
AU  - Julianne V. Kus
AU  - Pegah Mosharaf Ghahfarokhy
AU  - Julieta Munoz
AU  - Daniel J. Floyd
AU  - Diego Fuentes-Palacios
AU  - Samuel M. Gonçalves
AU  - Relber A. Gonçales
AU  - Mostafa Salehi
AU  - Jigar V. Desai
AU  - Agostinho Carvalho
AU  - Shenglin Mei
AU  - Carol A. Munro
AU  - Alex Hopke
AU  - Toni Gabaldón
AU  - Attila Gacser
AU  - Oliver Kurzai
AU  - Geraldine Butler
AU  - David S. Perlin
AU  - Wenjie Fang
AU  - Clarissa J. Nobile
AU  - Michael K. Mansour
AU  - Amir Arastehfar
PY  - 2026
DA  - 2026/09/01
JO  - PLOS Biology
DO  - 10.1371/journal.pbio.3003973
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003973
AB  - Candida parapsilosis is a major human fungal pathogen, with recent global outbreaks driven by fluconazole-resistant (FLCR-Cp) isolates that are difficult to eradicate and associated with poor clinical outcomes. However, the microbial traits enabling persistence of these outbreak lineages remain poorly defined. Here, we show that FLCR-Cp isolates responsible for prolonged, multi-country outbreaks consistently exhibit a striking low-biofilm-producing (LBP) phenotype. Contrary to the prevailing view that robust biofilm formation promotes persistence, LBP strains displayed enhanced stress tolerance, increased cell wall masking, and reduced immune recognition. These traits conferred resistance to neutrophil and macrophage killing and enhanced survival in immune cell-rich organs during systemic infection. Genome-wide transcriptomic profiling revealed extensive metabolic and regulatory rewiring in LBP strains. Whole-genome sequencing (WGS) of a global isolate collection further demonstrated that the LBP phenotype has emerged independently multiple times, supporting convergent evolution under host selection. Functional genomic analyses suggest that biofilm attenuation arises through multigenic changes, and disruption of key biofilm-associated transcriptional regulators enhanced fitness during immune interactions. Together, our findings overturn the assumption that robust biofilm formation drives outbreak persistence and instead identify biofilm attenuation as an adaptive tradeoff that promotes immune evasion and long-term survival. These results redefine our understanding of C. parapsilosis adaptation during healthcare-associated outbreaks and shift attention toward host-driven evolutionary processes than environmental persistence alone.  Drug-resistant Candida parapsilosis is an increasing problem in hospitals, but what traits help fungus survive? This study shows that reduced biofilm formation is repeatedly selected for during infection and helps C. parapsilosis evade immune defenses and persist in the host.
SN  - 1545-7885
ER  -