In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species DOI Creative Commons
Yuchen Wang,

Xi Guo,

X Zhang

et al.

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(8), P. 815 - 815

Published: Aug. 2, 2023

Ten Candida species strains were isolated from the first known fatal case of rhinofacial and rhino–orbital–cerebral candidiasis. Among them, five parapsilosis complex during early stage hospitalization, while tropicalis in later stages disease. Using whole-genome sequencing, we distinguished C. as four metapsilosis one strain. Antifungal susceptibility testing showed that susceptible to all antifungal drugs, had high minimum inhibitory concentrations azoles, whereas antifungal-drug resistance gene analysis revealed causes azole such strains. For time, analyzed microevolutionary characteristics pathogenic fungi human hosts inferred infection time parallel evolution Molecular clock azole-resistant occurred round therapy, followed by divergence via vivo. The presence/absence variations indicated a potential decrease virulence genomes following drug treatment, despite absence observed clinical improvement conditions patient. These results suggest genomic could serve an auxiliary tool guiding diagnosis treatment.

Language: Английский

Oxidative stress response pathways in fungi DOI
Hajar Yaakoub, Sara Mina,

Alphonse Calenda

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(6)

Published: June 1, 2022

Language: Английский

Citations

79

Shifts in Mutation Bias Promote Mutators by Altering the Distribution of Fitness Effects DOI
Marwa Z. Tuffaha,

Saranya Varakunan,

David Castellano

et al.

The American Naturalist, Journal Year: 2023, Volume and Issue: 202(4), P. 503 - 518

Published: May 18, 2023

AbstractRecent experimental evidence demonstrates that shifts in mutational biases-for example, increases transversion frequency-can change the distribution of fitness effects mutations (DFE). In particular, reducing or reversing a prevailing bias can increase probability de novo mutation is beneficial. It has also been shown mutator bacteria are more likely to emerge if beneficial they generate have larger effect size than observed wild type. Here, we connect these two results, demonstrating strains reduce reverse positively shifted DFE, which turn dramatically their emergence probability. Since changes rate and often coupled through gain loss DNA repair enzymes, our results predict invasion will be facilitated by offer improved access previously undersampled mutations.

Language: Английский

Citations

12

Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice DOI Creative Commons
Gemma Bellı́, Neus Colomina, Laia Castells‐Roca

et al.

Journal of Fungi, Journal Year: 2022, Volume and Issue: 8(6), P. 621 - 621

Published: June 10, 2022

The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of lesions. Post-translational modifications play crucial role in channeling damage tolerance (DDT) repair mechanisms bypass unrepaired lesions promote optimal fork restart. ubiquitination processes trigger following two main DDT sub-pathways: Rad6/Rad18-dependent monoubiquitination Ubc13-Mms2/Rad5-mediated polyubiquitination, promoting error-prone translation synthesis (TLS) or error-free template switch (TS) pathways, respectively. However, protection mechanism leading TS during reversal still poorly understood. In contrast, sumoylation impedes homologous recombination (HR)-mediated salvage (SR) pathway. Focusing on Saccharomyces cerevisiae budding yeast, we summarized related-DDT that coordinately sustain stability cell survival. addition, compared sequences from various fungal pathogens, considering recent advances structural features. Importantly, identification epitopes may lead potential targets for antifungal drug development.

Language: Английский

Citations

12

Examination of Gene Loss in the DNA Mismatch Repair Pathway and Its Mutational Consequences in a Fungal Phylum DOI Creative Commons
Megan Phillips, Jacob L. Steenwyk, Xing‐Xing Shen

et al.

Genome Biology and Evolution, Journal Year: 2021, Volume and Issue: 13(10)

Published: Sept. 21, 2021

The DNA mismatch repair (MMR) pathway corrects mismatched bases produced during replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss function in one or a few MMR genes can lead to increased mutation rates microsatellite instability, as seen some human cancers. Although loss has been documented context disease hypermutant strains pathogens, examples entire species lineages that have experienced substantial gene are lacking. We examined genomes 1,107 fungal phylum Ascomycota presence 52 known be involved fungi. found median ascomycete contained 49/52 genes. In contrast, four closely related obligate plant parasites from powdery mildew genera Erysiphe Blumeria, lost between five 21 genes, including MLH3, EXO1, DPB11. span functions, include all other ascomycetes, any these alone previously linked rate. Consistent with hypothesis impairs function, we higher levels exhibit numbers mononucleotide runs, longer microsatellites, accelerated sequence evolution, elevated mutational bias A|T direction, decreased GC content. These results identify striking example macroevolutionary multiple eukaryotic lineage, even though outcomes losses appear resemble those associated detrimental dysfunction organisms.

Language: Английский

Citations

15

Natural trait variation across Saccharomycotina species DOI Creative Commons
Jun Ting Johnson Wang, Jacob L. Steenwyk, Rachel B. Brem

et al.

FEMS Yeast Research, Journal Year: 2024, Volume and Issue: 24

Published: Jan. 1, 2024

Among molecular biologists, the group of fungi called Saccharomycotina is famous for its yeasts. These yeasts in turn are what they have common-genetic, biochemical, and cell-biological characteristics that serve as models plants animals. But behind apparent homogeneity species lie a wealth differences. In this review, we discuss traits vary across subphylum. We describe cases bright pigmentation; zoo cell shapes; metabolic specialties; with unique rules gene regulation. genetics diversity why it matters, including insights into basic evolutionary principles relevance Eukarya.

Language: Английский

Citations

1

Iron necessity for chlamydospore germination in Fusarium oxysporum f. sp. cubense TR4 DOI Creative Commons
Evans Were, Altus Viljoen, Frank Rasche

et al.

BioMetals, Journal Year: 2023, Volume and Issue: 36(6), P. 1295 - 1306

Published: June 29, 2023

Abstract Fusarium wilt disease of banana, caused by the notorious soil-borne pathogen oxysporum f. sp. cubense Tropical Race 4 (Foc TR4), is extremely difficult to manage. Manipulation soil pH or application synthetic iron chelators can suppress through starvation, which inhibits germination propagules called chlamydospores. However, effect starvation on chlamydospore largely unknown. In this study, scanning electron microscopy was used assemble developmental sequence and assess in vitro . Germination occurs three distinct phenotypic transitions (swelling, polarized growth, outgrowth). Outgrowth, characterized formation a single protrusion (germ tube), occurred at 2 3 h, maximum value 69.3% 76.7% outgrowth observed 8 10 h after induction. exhibited plasticity with as over 60% chlamydospores formed germ tube between 11. Iron-starved polarized-growth arrest, inability form tube. Gene expression analysis rnr1 rnr2 , encode iron-dependent enzyme ribonucleotide reductase, showed that upregulated (p < 0.0001) iron-starved compared control. Collectively, these findings suggest extracellular are crucial for Foc TR4. Moreover, inhibition may be linked different mechanism, rather than repression function controls growth regulation DNA synthesis.

Language: Английский

Citations

3

Shifts in mutation bias promote mutators by altering the distribution of fitness effects DOI Creative Commons
Marwa Z. Tuffaha,

Saranya Varakunan,

David Castellano

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 28, 2022

Abstract Recent experimental evidence demonstrates that shifts in mutational biases, for example increases transversion frequency, can change the distribution of fitness effects mutations (DFE). In particular, reducing or reversing a prevailing bias increase probability de novo mutation is beneficial. It has also been shown mutator bacteria are more likely to emerge if beneficial they generate have larger effect size than observed wildtype. Here, we connect these two results, demonstrating strains reduce reverse positively-shifted DFE, which turn dramatically their emergence probability. Since changes rate and often coupled through gain loss DNA repair enzymes, our results predict invasion will be facilitated by offer improved access previously under-sampled mutations.

Language: Английский

Citations

5

Examination of gene loss in the DNA mismatch repair pathway and its mutational consequences in a fungal phylum DOI Creative Commons
Megan Phillips, Jacob L. Steenwyk, Xing‐Xing Shen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: April 14, 2021

Abstract The DNA mismatch repair (MMR) pathway corrects mismatched bases produced during replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss function in one or a few MMR genes can lead to increased mutation rates microsatellite instability, as seen some human cancers. While loss has been documented context disease hypermutant strains pathogens, examples entire species lineages that have experienced substantial gene are lacking. We examined genomes 1,107 fungal phylum Ascomycota presence 52 known be involved fungi. found median ascomycete contained 49 / genes. In contrast, four closely related obligate plant parasites from powdery mildew genera Erysiphe Blumeria , lost between 5 21 genes, including MLH3 EXO1 DPB11 . span functions, include all other ascomycetes, any these alone previously linked rate. Consistent with hypothesis impairs function, we higher levels exhibit numbers mononucleotide runs, longer microsatellites, accelerated sequence evolution, elevated mutational bias A|T direction, decreased GC content. These results identify striking example macroevolutionary multiple eukaryotic lineage, even though outcomes losses appear resemble those associated detrimental dysfunction organisms. Significance Statement nucleotide base errors occur DNA; leads cancer. conservation pathway’s more than 1,000 lineage mildews, group fungi infect leaves plants, which extensive multiple, otherwise conserved, mildews show diverse types mutation, raising organisms diversified while lacking thought essential accurate DNA.

Language: Английский

Citations

4

The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata DOI Creative Commons
Qi Ni, Xianwei Wu,

Tongxuan Su

et al.

BMC Microbiology, Journal Year: 2023, Volume and Issue: 23(1)

Published: Oct. 28, 2023

Abstract Background Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due its high prevalence and drug resistance in recent years. C. developed many strategies evade the clearance of host immune system, thereby causing persistent infection. Although coping with induced DNA damage is widely acknowledged be important, underlying mechanisms remain unclear. Results The present study provides hitherto undocumented evidence importance regulatory subunits CgCK2 (CgCkb1 CgCkb2) response damage. Deletion Cg CKB1 or CKB2 enhanced cellular apoptosis breaks led cell cycle delay. In addition, deficiencies survival upon phagocytosis were observed Δ ckb1 ckb2 strains. Consistently, disruption attenuated virulence mouse models invasive candidiasis. Furthermore, global transcriptional profiling analysis revealed that CgCkb1 CgCkb2 participate resumption genomic stability. Conclusions Overall, our findings suggest stress crucial for survive macrophages, leading full vivo. significance this work lies providing a better understanding pathogenicity -related candidiasis expanding ideas clinical therapies.

Language: Английский

Citations

1

In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species DOI Creative Commons
Yuchen Wang,

Xi Guo,

X Zhang

et al.

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(8), P. 815 - 815

Published: Aug. 2, 2023

Ten Candida species strains were isolated from the first known fatal case of rhinofacial and rhino–orbital–cerebral candidiasis. Among them, five parapsilosis complex during early stage hospitalization, while tropicalis in later stages disease. Using whole-genome sequencing, we distinguished C. as four metapsilosis one strain. Antifungal susceptibility testing showed that susceptible to all antifungal drugs, had high minimum inhibitory concentrations azoles, whereas antifungal-drug resistance gene analysis revealed causes azole such strains. For time, analyzed microevolutionary characteristics pathogenic fungi human hosts inferred infection time parallel evolution Molecular clock azole-resistant occurred round therapy, followed by divergence via vivo. The presence/absence variations indicated a potential decrease virulence genomes following drug treatment, despite absence observed clinical improvement conditions patient. These results suggest genomic could serve an auxiliary tool guiding diagnosis treatment.

Language: Английский

Citations

0