Candida infections are a major clinical challenge in critically ill patients in intensive care units (ICUs), where impaired host defences, invasive procedures, and broad-spectrum antimicrobials exposu...

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 infect...

by Farnaz Daneshnia, Deepika Gunasekaran, Sean Bergin, Lisa Lombardi, Austin M. Perry, Liuyang Cai, Louise A. Walker, Tibor Nemeth, Süleyha Hilmioglu-Polat, Letal I. Salzberg, Arefeh Ebadati, Tobias Köhler, Gabriel Braune, João N. de Almeida, Giuseppina Caggiano, Julianne V. Kus, Pegah Mosharaf Ghahfarokhy, Julieta Munoz, Daniel J. Floyd, Diego Fuentes-Palacios, Samuel M. Gonçalves, Relber A. Gonçales, Mostafa Salehi, Jigar V. Desai, Agostinho Carvalho, Shenglin Mei, Carol A. Munro, Alex Hopke, Toni Gabaldón, Attila Gacser, Oliver Kurzai, Geraldine Butler, David S. Perlin, Wenjie Fang, Clarissa J. Nobile, Michael K. Mansour, Amir Arastehfar 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.

by Farnaz Daneshnia, Deepika Gunasekaran, Sean Bergin, Lisa Lombardi, Austin M. Perry, Liuyang Cai, Louise A. Walker, Tibor Nemeth, Süleyha Hilmioglu-Polat, Letal I. Salzberg, Arefeh Ebadati, Tobias Köhler, Gabriel Braune, João N. de Almeida, Giuseppina Caggiano, Julianne V. Kus, Pegah Mosharaf Ghahfarokhy, Julieta Munoz, Daniel J. Floyd, Diego Fuentes-Palacios, Samuel M. Gonçalves, Relber A. Gonçales, Mostafa Salehi, Jigar V. Desai, Agostinho Carvalho, Shenglin Mei, Carol A. Munro, Alex Hopke, Toni Gabaldón, Attila Gacser, Oliver Kurzai, Geraldine Butler, David S. Perlin, Wenjie Fang, Clarissa J. Nobile, Michael K. Mansour, Amir Arastehfar 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.

Trabalho conduzido na Unifran demonstrou forte sinergismo entre antisséptico e compostos como eugenol e mentol no combate ao fungo Candida parapsilosis

by Farnaz Daneshnia, Deepika Gunasekaran, Sean Bergin, Lisa Lombardi, Austin M. Perry, Liuyang Cai, Louise A. Walker, Tibor Nemeth, Süleyha Hilmioglu-Polat, Letal I. Salzberg, Arefeh Ebadati, Tobias Köhler, Gabriel Braune, João N. de Almeida, Giuseppina Caggiano, Julianne V. Kus, Pegah Mosharaf Ghahfarokhy, Julieta Munoz, Daniel J. Floyd, Diego Fuentes-Palacios, Samuel M. Gonçalves, Relber A. Gonçales, Mostafa Salehi, Jigar V. Desai, Agostinho Carvalho, Shenglin Mei, Carol A. Munro, Alex Hopke, Toni Gabaldón, Attila Gacser, Oliver Kurzai, Geraldine Butler, David S. Perlin, Wenjie Fang, Clarissa J. Nobile, Michael K. Mansour, Amir Arastehfar 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 infect...

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 infect...

Published in PLoS biology

<span><b>Introduction.</b> Hospital-acquired infections (HAIs) frequently manifest as device-related biofilms that exhibit enhanced tolerance to conventional therapies contributing to antimicrobial resistance....