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Article ; Online: A 'parameiosis' drives depolyploidization and homologous recombination in Candida albicans.

Anderson, Matthew Z / Thomson, Gregory J / Hirakawa, Matthew P / Bennett, Richard J

2019 Volume 10, Issue 1, Page(s) 4388

Abstract: Meiosis is a conserved tenet of sexual reproduction in eukaryotes, yet this program is seemingly absent from many extant species. In the human fungal pathogen Candida albicans, mating of diploid cells generates tetraploid products that return to the ... ...

Abstract	Meiosis is a conserved tenet of sexual reproduction in eukaryotes, yet this program is seemingly absent from many extant species. In the human fungal pathogen Candida albicans, mating of diploid cells generates tetraploid products that return to the diploid state via a non-meiotic process of depolyploidization known as concerted chromosome loss (CCL). Here, we report that recombination rates are more than three orders of magnitude higher during CCL than during normal mitotic growth. Furthermore, two conserved 'meiosis-specific' factors play central roles in CCL as SPO11 mediates DNA double-strand break formation while both SPO11 and REC8 regulate chromosome stability and promote inter-homolog recombination. Unexpectedly, SPO11 also promotes DNA repair and recombination during normal mitotic divisions. These results indicate that C. albicans CCL represents a 'parameiosis' that blurs the conventional boundaries between mitosis and meiosis. They also reveal parallels with depolyploidization in mammalian cells and provide potential insights into the evolution of meiosis.
MeSH term(s)	Candida albicans/genetics ; Candidiasis/microbiology ; Chromosomes, Fungal/genetics ; DNA Damage ; Diploidy ; Endodeoxyribonucleases/genetics ; Endodeoxyribonucleases/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Homologous Recombination/genetics ; Humans ; Meiosis/genetics ; Mitosis/genetics ; Rec A Recombinases/genetics ; Rec A Recombinases/metabolism ; Recombinational DNA Repair ; Tetraploidy
Chemical Substances	Fungal Proteins ; Rec A Recombinases (EC 2.7.7.-) ; Endodeoxyribonucleases (EC 3.1.-) ; meiotic recombination protein SPO11 (EC 3.1.-)
Language	English
Publishing date	2019-09-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-12376-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Phenothiazines Rapidly Induce Laccase Expression and Lignin-Degrading Properties in the White-Rot Fungus

Hirakawa, Matthew P / Rodriguez, Alberto / Tran-Gyamfi, Mary B / Light, Yooli K / Martinez, Salvador / Diamond-Pott, Henry / Simmons, Blake A / Sale, Kenneth L

Journal of fungi (Basel, Switzerland)

2023 Volume 9, Issue 3

Abstract: ... Phlebia ... ...

Abstract	Phlebia radiata
Language	English
Publishing date	2023-03-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof9030371
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Article ; Online: Adaptation to the dietary sugar D-tagatose via genome instability in polyploid Candida albicans cells.

Thomson, Gregory J / Kakade, Pallavi / Hirakawa, Matthew P / Ene, Iuliana V / Bennett, Richard J

G3 (Bethesda, Md.)

2021 Volume 11, Issue 7

Abstract: The opportunistic fungal pathogen Candida albicans undergoes an unusual parasexual cycle wherein diploid cells mate to form tetraploid cells that can generate genetically diverse progeny via a nonmeiotic program of chromosome loss. The genetic diversity ... ...

Abstract	The opportunistic fungal pathogen Candida albicans undergoes an unusual parasexual cycle wherein diploid cells mate to form tetraploid cells that can generate genetically diverse progeny via a nonmeiotic program of chromosome loss. The genetic diversity afforded by parasex impacts clinically relevant features including drug resistance and virulence, and yet the factors influencing genome instability in C. albicans are not well defined. To understand how environmental cues impact genome instability, we monitored ploidy change following tetraploid cell growth in a panel of different carbon sources. We found that growth in one carbon source, D-tagatose, led to high levels of genomic instability and chromosome loss in tetraploid cells. This sugar is a stereoisomer of L-sorbose which was previously shown to promote karyotypic changes in C. albicans. However, while expression of the SOU1 gene enabled utilization of L-sorbose, overexpression of this gene did not promote growth in D-tagatose, indicating differences in assimilation of the two sugars. In addition, genome sequencing of multiple progenies recovered from D-tagatose cultures revealed increased relative copy numbers of chromosome 4, suggestive of chromosome-level regulation of D-tagatose metabolism. Together, these studies identify a novel environmental cue that induces genome instability in C. albicans, and further implicate chromosomal changes in supporting metabolic adaptation in this species.
MeSH term(s)	Candida albicans/metabolism ; Sorbose/metabolism ; Tetraploidy ; Dietary Sugars/metabolism ; Genomic Instability ; Polyploidy ; Carbon/metabolism
Chemical Substances	Sorbose (NV2001607Y) ; tagatose (T7A20Y888Y) ; Dietary Sugars ; Carbon (7440-44-0)
Language	English
Publishing date	2021-04-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkab110
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sub-4 nm mapping of donor-acceptor organic semiconductor nanoparticle composition.

Persson, Ingemar / Laval, Hugo / Chambon, Sylvain / Bonfante, Gwenael / Hirakawa, Kazuhiko / Wantz, Guillaume / Watts, Benjamin / Marcus, Matthew A / Xu, Xiaoxue / Ying, Lei / Lakhwani, Girish / Andersson, Mats R / Cairney, Julie M / Holmes, Natalie P

Nanoscale

2023 Volume 15, Issue 13, Page(s) 6126–6142

Abstract: We report, for the first time, sub-4 nm mapping of donor : acceptor nanoparticle composition in eco-friendly colloidal dispersions for organic electronics. Low energy scanning transmission electron microscopy (STEM) energy dispersive X-ray spectroscopy ( ... ...

Abstract	We report, for the first time, sub-4 nm mapping of donor : acceptor nanoparticle composition in eco-friendly colloidal dispersions for organic electronics. Low energy scanning transmission electron microscopy (STEM) energy dispersive X-ray spectroscopy (EDX) mapping has revealed the internal morphology of organic semiconductor donor : acceptor blend nanoparticles at the sub-4 nm level. A unique element was available for utilisation as a fingerprint element to differentiate donor from acceptor material in each blend system. Si was used to map the location of donor polymer PTzBI-Si in PTzBI-Si:N2200 nanoparticles, and S (in addition to N) was used to map donor polymer TQ1 in TQ1:PC
Language	English
Publishing date	2023-03-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2515664-0
ISSN	2040-3372 ; 2040-3364
ISSN (online)	2040-3372
ISSN	2040-3364
DOI	10.1039/d3nr00839h
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Article ; Online: A ‘parameiosis’ drives depolyploidization and homologous recombination in Candida albicans

Matthew Z. Anderson / Gregory J. Thomson / Matthew P. Hirakawa / Richard J. Bennett

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 10

Abstract: Mating of Candida albicans produces tetraploid products that return to the diploid state via a non-meiotic process known as concerted chromosome loss (CCL). Here, Anderson et al. show high recombination rates during CCL and identify factors that are ... ...

Abstract	Mating of Candida albicans produces tetraploid products that return to the diploid state via a non-meiotic process known as concerted chromosome loss (CCL). Here, Anderson et al. show high recombination rates during CCL and identify factors that are essential for chromosome stability and recombination during CCL.
Keywords	Science ; Q
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A ‘parameiosis’ drives depolyploidization and homologous recombination in Candida albicans

Matthew Z. Anderson / Gregory J. Thomson / Matthew P. Hirakawa / Richard J. Bennett

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 10

Abstract	Mating of Candida albicans produces tetraploid products that return to the diploid state via a non-meiotic process known as concerted chromosome loss (CCL). Here, Anderson et al. show high recombination rates during CCL and identify factors that are essential for chromosome stability and recombination during CCL.
Keywords	Science ; Q
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gene editing and CRISPR in the clinic: current and future perspectives.

Hirakawa, Matthew P / Krishnakumar, Raga / Timlin, Jerilyn A / Carney, James P / Butler, Kimberly S

Bioscience reports

2020 Volume 40, Issue 4

Abstract: Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly ... ...

Abstract	Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases which require cell modification in vivo. However, in vivo use of CRISPR technologies can be confounded by problems such as off-target editing, inefficient or off-target delivery, and stimulation of counterproductive immune responses. Current research addressing these issues may provide new opportunities for use of CRISPR in the clinical space. In this review, we examine the current status and scientific basis of clinical trials featuring ZFNs, TALENs, and CRISPR-based genome editing, the known limitations of CRISPR use in humans, and the rapidly developing CRISPR engineering space that should lay the groundwork for further translation to clinical application.
MeSH term(s)	Animals ; CRISPR-Cas Systems/genetics ; Cell Culture Techniques ; Clinical Trials as Topic ; Drug Delivery Systems/methods ; Drug Delivery Systems/trends ; Gene Editing/methods ; Gene Editing/trends ; Genetic Therapy/methods ; Genetic Therapy/trends ; Genetic Vectors/administration & dosage ; Genetic Vectors/genetics ; Humans ; Immunotherapy, Adoptive/methods ; Immunotherapy, Adoptive/trends ; Mice ; Models, Animal ; Nanoparticles ; Receptors, Chimeric Antigen/genetics ; Transcription Activator-Like Effector Nucleases/genetics ; Translational Research, Biomedical/methods ; Translational Research, Biomedical/trends ; Zinc Finger Nucleases/genetics
Chemical Substances	Receptors, Chimeric Antigen ; Transcription Activator-Like Effector Nucleases (EC 3.1.-) ; Zinc Finger Nucleases (EC 3.1.-)
Language	English
Publishing date	2020-03-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20200127
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Phenothiazines Rapidly Induce Laccase Expression and Lignin-Degrading Properties in the White-Rot Fungus Phlebia radiata

Matthew P. Hirakawa / Alberto Rodriguez / Mary B. Tran-Gyamfi / Yooli K. Light / Salvador Martinez / Henry Diamond-Pott / Blake A. Simmons / Kenneth L. Sale

Journal of Fungi, Vol 9, Iss 371, p

2023 Volume 371

Abstract: ... conducted to identify chemical inducers of laccase expression in P. radiata . Among the chemicals tested ... phenothiazines were observed to induce laccase activity in P. radiata, with promethazine being the strongest ... treated P. radiata exhibited increased laccase protein abundance, increased enzymatic activity, and ...

Abstract	Phlebia radiata is a widespread white-rot basidiomycete fungus with significance in diverse biotechnological applications due to its ability to degrade aromatic compounds, xenobiotics, and lignin using an assortment of oxidative enzymes including laccase. In this work, a chemical screen with 480 conditions was conducted to identify chemical inducers of laccase expression in P. radiata . Among the chemicals tested, phenothiazines were observed to induce laccase activity in P. radiata, with promethazine being the strongest laccase inducer of the phenothiazine-derived compounds examined. Secretomes produced by promethazine-treated P. radiata exhibited increased laccase protein abundance, increased enzymatic activity, and an enhanced ability to degrade phenolic model lignin compounds. Transcriptomics analyses revealed that promethazine rapidly induced the expression of genes encoding lignin-degrading enzymes, including laccase and various oxidoreductases, showing that the increased laccase activity was due to increased laccase gene expression. Finally, the generality of promethazine as an inducer of laccases in fungi was demonstrated by showing that promethazine treatment also increased laccase activity in other relevant fungal species with known lignin conversion capabilities including Trametes versicolor and Pleurotus ostreatus.
Keywords	white-rot fungi ; laccase ; lignin ; phenothiazine ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Upregulation of CD14 in mesenchymal stromal cells accelerates lipopolysaccharide-induced response and enhances antibacterial properties.

Hirakawa, Matthew P / Tjahjono, Nikki / Light, Yooli K / Celebi, Aleyna N / Celebi, Nisa N / Chintalapudi, Prem / Butler, Kimberly S / Branda, Steven S / Krishnakumar, Raga

iScience

2022 Volume 25, Issue 2, Page(s) 103759

Abstract: Mesenchymal stromal cells (MSCs) have broad-ranging therapeutic properties, including the ability to inhibit bacterial growth and resolve infection. However, the genetic mechanisms regulating these antibacterial properties in MSCs are largely unknown. ... ...

Abstract	Mesenchymal stromal cells (MSCs) have broad-ranging therapeutic properties, including the ability to inhibit bacterial growth and resolve infection. However, the genetic mechanisms regulating these antibacterial properties in MSCs are largely unknown. Here, we utilized a systems-based approach to compare MSCs from different genetic backgrounds that displayed differences in antibacterial activity. Although both MSCs satisfied traditional MSC-defining criteria, comparative transcriptomics and quantitative membrane proteomics revealed two unique molecular profiles. The antibacterial MSCs responded rapidly to bacterial lipopolysaccharide (LPS) and had elevated levels of the LPS co-receptor CD14. CRISPR-mediated overexpression of endogenous CD14 in MSCs resulted in faster LPS response and enhanced antibacterial activity. Single-cell RNA sequencing of CD14-upregulated MSCs revealed a shift in transcriptional ground state and a more uniform LPS-induced response. Our results highlight the impact of genetic background on MSC phenotypic diversity and demonstrate that overexpression of CD14 can prime these cells to be more responsive to bacterial challenge.
Language	English
Publishing date	2022-01-12
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103759
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Article ; Online: Upregulation of CD14 in mesenchymal stromal cells accelerates lipopolysaccharide-induced response and enhances antibacterial properties

Matthew P. Hirakawa / Nikki Tjahjono / Yooli K. Light / Aleyna N. Celebi / Nisa N. Celebi / Prem Chintalapudi / Kimberly S. Butler / Steven S. Branda / Raga Krishnakumar

iScience, Vol 25, Iss 2, Pp 103759- (2022)

2022

Abstract: Summary: Mesenchymal stromal cells (MSCs) have broad-ranging therapeutic properties, including the ability to inhibit bacterial growth and resolve infection. However, the genetic mechanisms regulating these antibacterial properties in MSCs are largely ... ...

Abstract	Summary: Mesenchymal stromal cells (MSCs) have broad-ranging therapeutic properties, including the ability to inhibit bacterial growth and resolve infection. However, the genetic mechanisms regulating these antibacterial properties in MSCs are largely unknown. Here, we utilized a systems-based approach to compare MSCs from different genetic backgrounds that displayed differences in antibacterial activity. Although both MSCs satisfied traditional MSC-defining criteria, comparative transcriptomics and quantitative membrane proteomics revealed two unique molecular profiles. The antibacterial MSCs responded rapidly to bacterial lipopolysaccharide (LPS) and had elevated levels of the LPS co-receptor CD14. CRISPR-mediated overexpression of endogenous CD14 in MSCs resulted in faster LPS response and enhanced antibacterial activity. Single-cell RNA sequencing of CD14-upregulated MSCs revealed a shift in transcriptional ground state and a more uniform LPS-induced response. Our results highlight the impact of genetic background on MSC phenotypic diversity and demonstrate that overexpression of CD14 can prime these cells to be more responsive to bacterial challenge.
Keywords	Molecular biology ; Cell biology ; Omics ; Science ; Q
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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