Host-derived Reactive Nitrogen Species mediate the Cryptococcus neoformans yeast-to-titan switch via fungal-derived superoxide DOI Creative Commons
Xin Zhou, Guillaume E. Desanti, Robin C. May

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Март 1, 2021

Abstract In the host lung, human fungal pathogen Cryptococcus neoformans undergoes a morphological switch from small haploid yeast to large polyploid titan cell, contributing C. virulence. Titan cells are less readily phagocytosed and can survive nitrosative oxidative stresses. We others previously showed that titanization is triggered by host-relevant signals including CO 2 lung-resident bacteria, addition of these factor sufficient induce in vitro . Here we investigate molecular mechanisms drive this transition demonstrate host-derived immune increase degree frequency titanization. Specifically, reactive nitrogen species accumulation endogenous superoxide within cryptococcal cells, particularly nuclei, where it cause genotoxic stress. Consistent with this, observe Rad51 protein, marker double strand break repair pathway, titanizing cultures. Blocking inhibits titanization, yet also requires detoxification through Superoxide Dismutase (SOD) activity. Loss mitochondrial Sod2 activity locks phase, while Sod1 required for production viable daughter cells. hypothesize redox responsive transcription Yap1 part mediates response regulating SOD2/SOD1 addition, show translocates nucleus, likely involved superoxide. Together, findings reveal major new regulatory mechanism yeast-to-titan transition. Author Summary During infection, phagocytes produce oxygen (ROS/RNS), determinants infection outcome. Fungal pathogens have developed numerous strategies neutralize detoxify ROS, but RNS remain important effectors control. undergo highly increased ROS/RNS stress resistance, capacity or aneuploid daughters. Here, report signal driving act increasing ROS fungus. transition, associated leading polyploidy. Yet, failure either mutants defective protein Yap1, impairs cell budding reduces progeny viability. Therefore, interface exogenous regulation during host-pathogen interaction represents an Achilles’ heel pathogen.

Язык: Английский

Quorum Sensing in Fungal Species DOI
Xiuyun Tian, Hao Ding, Weixin Ke

и другие.

Annual Review of Microbiology, Год журнала: 2021, Номер 75(1), С. 449 - 469

Опубликована: Авг. 4, 2021

Quorum sensing (QS) is one of the most studied cell-cell communication mechanisms in fungi. Research last 20 years has explored various fungal QS systems that are involved a wide range biological processes, especially eukaryote- or fungus-specific behaviors, mirroring significant contribution regulation to biology and evolution. Based on recent progress, we summarize this review regulation, with an emphasis its functional role behaviors unique fungi eukaryotes. We suggest using as genetically amenable eukaryotic model address why how integrated into reproductive strategies molecular cellular processes could be important direction for research.

Язык: Английский

Процитировано

60
Advances in understanding the evolution of fungal genome architecture DOI Creative Commons
Shelby Priest, Vikas Yadav, Joseph Heitman

и другие.

F1000Research, Год журнала: 2020, Номер 9, С. 776 - 776

Опубликована: Июль 27, 2020

Diversity within the fungal kingdom is evident from wide range of morphologies fungi display as well various ecological roles and industrial purposes they serve. Technological advances, particularly in long-read sequencing, coupled with increasing efficiency decreasing costs across sequencing platforms have enabled robust characterization genomes. These efforts continue to reveal rampant diversity at genome level. Here, we discuss studies that furthered our understanding genetic genomic evolution. revealed presence both small-scale large-scale changes. In fungi, research has recently focused on many changes, such how hypermutation allelic transmission impact evolution why a few specific regions are more susceptible rapid than others. High-throughput diverse set genomes also illuminated frequency, mechanisms, impacts which include chromosome structural variation changes number, aneuploidy, polyploidy, supernumerary chromosomes. The discussed herein provided great insight into architecture varies species modern may evolved last common ancestor might pave way for all domains life.

Язык: Английский

Процитировано

51
Immunoprotection against Cryptococcosis Offered by Znf2 Depends on Capsule and the Hyphal Morphology DOI
Jianfeng Lin, Tuyetnhu Pham,

Kenton Hipsher

и другие.

mBio, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 11, 2022

Cryptococcosis claims close to 200,000 lives annually. There is no vaccine clinically available for this fungal disease.

Язык: Английский

Процитировано

31
Identification of a protective antigen reveals the trade-off between iron acquisition and antigen exposure in a global fungal pathogen DOI Creative Commons

Yeqi Li,

Tuyetnhu Pham,

Kenton Hipsher

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(7)

Опубликована: Фев. 13, 2025

Systemic infections caused by Cryptococcus claim over 161,000 lives annually, with global mortality rate close to 70% despite antifungal therapies. Currently, no vaccine is available. To develop an effective multivalent against this free-living opportunistic eukaryotic pathogen, it critical identify protective antigens. We previously discovered ZNF2 oe strains elicit host immune responses and increase the abundance of antigens present in capsule, which required for its immunoprotection. Capsule a defining feature species composed polysaccharides mannoproteins. Here, we found increased levels exposed mannoproteins cells. As are primary components recognized anticryptococcal cell-mediated few have been characterized, systemically screened all 49 predicted GPI-mannoproteins neoformans enhanced recognition. identified those highly cells Cig1 be antigen cryptococcosis either as recombinant protein or mRNA vaccine. induced iron limitation expressed fungus infected mice patients cryptococcal meningitis. Remarkably, restriction induces express iron-uptake proteins including Cig1, act turn enhance detection. Our results highlight arms race between pathogen centered on competition, trade-off acquisition exposure. These findings demonstrate potential leveraging host–pathogen interaction development.

Язык: Английский

Процитировано

1
The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen Cryptococcus neoformans DOI Creative Commons
Ruoyan Liu, Xiaoyu Chen, Fujie Zhao

и другие.

Journal of Fungi, Год журнала: 2023, Номер 9(6), С. 672 - 672

Опубликована: Июнь 14, 2023

The Complex of Proteins Associated with Set1 (COMPASS) methylates lysine K4 on histone H3 (H3K4) and is conserved from yeast to humans. Its subunits regulatory roles in the meningitis-causing fungal pathogen Cryptococcus neoformans remain unknown. Here we identified core COMPASS complex C. deneoformans confirmed their H3K4 methylation. Through AlphaFold modeling, found that Set1, Bre2, Swd1, Swd3 form catalytic regulate cryptococcal yeast-to-hypha transition, thermal tolerance, virulence. complex-mediated methylation requires H2B mono-ubiquitination by Rad6/Bre1 Paf1 order activate expression genes specific for transition deneoformans. Taken together, our findings demonstrate putative function as a unified complex, contributing development

Язык: Английский

Процитировано

15
Cryptococcus neoformans: Sex, morphogenesis, and virulence DOI
Youbao Zhao, Xiaorong Lin

Infection Genetics and Evolution, Год журнала: 2021, Номер 89, С. 104731 - 104731

Опубликована: Янв. 23, 2021

Язык: Английский

Процитировано

29
Vaccination with a ZNF2 oe Strain of Cryptococcus Provides Long-Lasting Protection against Cryptococcosis and Is Effective in Immunocompromised Hosts DOI Creative Commons
Tuyetnhu Pham,

Yeqi Li,

Wendy T. Watford

и другие.

Infection and Immunity, Год журнала: 2023, Номер 91(7)

Опубликована: Июнь 20, 2023

Systemic cryptococcosis is fatal without treatment. Even with the current antifungal therapies, this disease kills 180,000 of 225,000 infected people annually. Exposure to causative environmental fungus Cryptococcus neoformans universal. Either reactivation a latent infection or an acute after high exposure cryptococcal cells can result in cryptococcosis. Currently, there no vaccine prevent Previously, we discovered that Znf2, transcription factor directs yeast-to-hypha transition, profoundly affects interaction host. Overexpression

Язык: Английский

Процитировано

13
The RAM signaling pathway links morphology, thermotolerance, and CO2 tolerance in the global fungal pathogen Cryptococcus neoformans DOI Creative Commons
Benjamin J Chadwick, Tuyetnhu Pham,

Xiaofeng Xie

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Ноя. 23, 2022

The environmental pathogen Cryptococcus neoformans claims over 180,000 lives each year. Survival of this basidiomycete at host CO 2 concentrations has only recently been considered an important virulence trait. Through screening gene knockout libraries constructed in a -tolerant clinical strain, we found mutations leading to sensitivity are enriched pathways activated by heat stress, including calcineurin, Ras1-Cdc24, cell wall integrity, and R egulator A ce2 M orphogenesis (RAM). Overexpression Cbk1, the conserved terminal kinase RAM pathway, partially restored defects these mutants or temperature levels. In ascomycetes such as Saccharomyces cerevisiae Candida albicans , transcription factor Ace2 is target activating genes responsible for separation. However, no homolog any downstream component pathway identified basidiomycetes. vitro evolution comparative genomics, characterized suppressors cbk1 Δ C. that rescued tolerance, thermotolerance, morphology. One suppressor RNA translation repressor Ssd1, which highly other novel ribonuclease domain-containing protein, here named PSC1 present basidiomycetes humans but surprisingly absent most ascomycetes. Loss Ssd1 cryptococcal ability survive amplify inhalation intravenous murine models cryptococcosis. Our discoveries highlight overlapping regulation tolerance essential role adaptation condition, potential importance post-transcriptional control traits global pathogen.

Язык: Английский

Процитировано

15
All hands on Dec: Treating cryptococcosis with dectin decorated liposomes loaded with antifungals DOI Creative Commons
Tuyetnhu Pham,

Ran Shi,

Suresh Ambati

и другие.

iScience, Год журнала: 2024, Номер 27(7), С. 110349 - 110349

Опубликована: Июнь 22, 2024

Язык: Английский

Процитировано

3
Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans DOI Open Access
Yixuan Jiang, Ying Liang, Fujie Zhao

и другие.

Опубликована: Апрель 15, 2025

Rtf1 is generally considered to be a subunit of the Paf1 complex (Paf1C), which multifunctional protein involved in histone modification and RNA biosynthesis at multiple stages. stably associated with Paf1C Saccharomyces cerevisiae , but not other species including humans. Little known about its function human fungal pathogens. Here, we show that required for facilitating H2B monoubiquitination (H2Bub1), regulates morphogenesis pathogenicity meningitis-causing pathogen Cryptococcus neoformans . tightly Paf1C, domain (HMD) sufficient promote H2Bub1 expression genes related mating filamentation. Moreover, HMD fully restores pathogenicity; however, it fails restore defects thermal tolerance melanin production rtf1 Δ strain background. The present study establishes role cryptococcal as Paf1C-independent regulator regulating pathogenicity, highlights global C.

Язык: Английский

Процитировано

0