Menu
×
Main Library
9 a.m. - 8 p.m.
Phone: (843) 805-6930
West Ashley Library
9 a.m. - 7 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed for renovations
Phone: (843) 588-2001
John L. Dart Library
9 a.m. - 7 p.m.
Phone: (843) 722-7550
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Mt. Pleasant Library
9 a.m. – 8 p.m.
Phone: (843) 849-6161
Dorchester Road Library
9 a.m. - 8 p.m.
Phone: (843) 552-6466
Edgar Allan Poe/Sullivan's Island Library
9 a.m. - 1 p.m.
Phone: (843) 883-3914
John's Island Library
9 a.m. - 8 p.m.
Phone: (843) 559-1945
McClellanville Library
Closed for renovations
Phone: (843) 887-3699
Edisto Library
2 p.m. - 6 p.m.
Phone: (843) 869-2355
Wando Mount Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 805-6888
Otranto Road Library
9 a.m. - 8 p.m.
Phone: (843) 572-4094
Hurd/St. Andrews Library
Closed (Toddler Storytime)
Phone: (843) 766-2546
Baxter-Patrick James Island
9 a.m. - 8 p.m.
Phone: (843) 795-6679
Bees Ferry West Ashley Library
9 a.m. - 8 p.m.
Phone: (843) 805-6892
Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
Keith Summey North Charleston Library
9 a.m. – 8 p.m.
Phone: (843) 744-2489
Mobile Library
9 a.m. - 5 p.m.
Phone: (843) 805-6909
Today's Hours
Main Library
9 a.m. - 8 p.m.
Phone: (843) 805-6930
West Ashley Library
9 a.m. - 7 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed for renovations
Phone: (843) 588-2001
John L. Dart Library
9 a.m. - 7 p.m.
Phone: (843) 722-7550
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Mt. Pleasant Library
9 a.m. – 8 p.m.
Phone: (843) 849-6161
Dorchester Road Library
9 a.m. - 8 p.m.
Phone: (843) 552-6466
Edgar Allan Poe/Sullivan's Island Library
9 a.m. - 1 p.m.
Phone: (843) 883-3914
John's Island Library
9 a.m. - 8 p.m.
Phone: (843) 559-1945
McClellanville Library
Closed for renovations
Phone: (843) 887-3699
Edisto Library
2 p.m. - 6 p.m.
Phone: (843) 869-2355
Wando Mount Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 805-6888
Otranto Road Library
9 a.m. - 8 p.m.
Phone: (843) 572-4094
Hurd/St. Andrews Library
Closed (Toddler Storytime)
Phone: (843) 766-2546
Baxter-Patrick James Island
9 a.m. - 8 p.m.
Phone: (843) 795-6679
Bees Ferry West Ashley Library
9 a.m. - 8 p.m.
Phone: (843) 805-6892
Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
Keith Summey North Charleston Library
9 a.m. – 8 p.m.
Phone: (843) 744-2489
Mobile Library
9 a.m. - 5 p.m.
Phone: (843) 805-6909
Patron Login
menu
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Author(s): Rodriguez L;Rodriguez L; Voorhies M; Voorhies M; Gilmore S; Gilmore S; Beyhan S; Beyhan S; Myint A; Myint A; Sil A; Sil A
- Source:
PLoS biology [PLoS Biol] 2019 Sep 30; Vol. 17 (9), pp. e3000168. Date of Electronic Publication: 2019 Sep 30 (Print Publication: 2019).- Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Retracted Publication- Language:
English - Source:
- Additional Information
- Source: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
- Publication Information: Original Publication: San Francisco, CA : Public Library of Science, [2003]-
- Subject Terms: Gene Expression Regulation, Fungal* ; Signal Transduction*; Histoplasma/*physiology ; Hyphae/*growth & development ; Mucins/*metabolism; Fungal Proteins/metabolism ; Gene Expression Profiling ; Genes, Fungal ; Histoplasma/cytology ; Mitogen-Activated Protein Kinases/metabolism ; Mucins/genetics ; Temperature
- Abstract: Phenotypic switching between 2 opposing cellular states is a fundamental aspect of biology, and fungi provide facile systems to analyze the interactions between regulons that control this type of switch. A long-standing mystery in fungal pathogens of humans is how thermally dimorphic fungi switch their developmental form in response to temperature. These fungi, including the subject of this study, Histoplasma capsulatum, are temperature-responsive organisms that utilize unknown regulatory pathways to couple their cell shape and associated attributes to the temperature of their environment. H. capsulatum grows as a multicellular hypha in the soil that switches to a pathogenic yeast form in response to the temperature of a mammalian host. These states can be triggered in the laboratory simply by growing the fungus either at room temperature (RT; which promotes hyphal growth) or at 37 °C (which promotes yeast-phase growth). Prior worked revealed that 15% to 20% of transcripts are differentially expressed in response to temperature, but it is unclear which transcripts are linked to specific phenotypic changes, such as cell morphology or virulence. To elucidate temperature-responsive regulons, we previously identified 4 transcription factors (required for yeast-phase growth [Ryp]1-4) that are required for yeast-phase growth at 37 °C; in each ryp mutant, the fungus grows constitutively as hyphae regardless of temperature, and the cells fail to express genes that are normally induced in response to growth at 37 °C. Here, we perform the first genetic screen to identify genes required for hyphal growth of H. capsulatum at RT and find that disruption of the signaling mucin MSB2 results in a yeast-locked phenotype. RNA sequencing (RNAseq) experiments reveal that MSB2 is not required for the majority of gene expression changes that occur when cells are shifted to RT. However, a small subset of temperature-responsive genes is dependent on MSB2 for its expression, thereby implicating these genes in the process of filamentation. Disruption or knockdown of an Msb2-dependent mitogen-activated protein (MAP) kinase (HOG2) and an APSES transcription factor (STU1) prevents hyphal growth at RT, validating that the Msb2 regulon contains genes that control filamentation. Notably, the Msb2 regulon shows conserved hyphal-specific expression in other dimorphic fungi, suggesting that this work defines a small set of genes that are likely to be conserved regulators and effectors of filamentation in multiple fungi. In contrast, a few yeast-specific transcripts, including virulence factors that are normally expressed only at 37 °C, are inappropriately expressed at RT in the msb2 mutant, suggesting that expression of these genes is coupled to growth in the yeast form rather than to temperature. Finally, we find that the yeast-promoting transcription factor Ryp3 associates with the MSB2 promoter and inhibits MSB2 transcript expression at 37 °C, whereas Msb2 inhibits accumulation of Ryp transcripts and proteins at RT. These findings indicate that the Ryp and Msb2 circuits antagonize each other in a temperature-dependent manner, thereby allowing temperature to govern cell shape and gene expression in this ubiquitous fungal pathogen of humans.
Competing Interests: The authors have declared that no competing interests exist. - Comments: Retraction in: PLoS Biol. 2023 Mar 21;21(3):e3002060. (PMID: 36944162)
- References: Mol Microbiol. 2015 Dec;98(5):910-929. (PMID: 26288377)
Environ Microbiol. 2010 Mar;12(3):810-20. (PMID: 20050869)
J Mol Biol. 2001 Dec 14;314(5):1041-52. (PMID: 11743721)
MBio. 2018 Apr 3;9(2):. (PMID: 29615501)
Mol Gen Genet. 1991 Jun;227(2):285-92. (PMID: 2062309)
Nucleic Acids Res. 2014 Dec 16;42(22):e168. (PMID: 25300484)
FEMS Yeast Res. 2018 Dec 1;18(8):. (PMID: 30101348)
Genome Biol. 2009;10(3):R25. (PMID: 19261174)
J Clin Microbiol. 1997 May;35(5):1071-6. (PMID: 9114383)
PLoS Genet. 2015 Oct 06;11(10):e1005493. (PMID: 26439490)
PLoS Genet. 2013;9(9):e1003799. (PMID: 24068964)
PLoS Genet. 2016 Oct 6;12(10):e1006353. (PMID: 27711197)
PLoS Genet. 2015 Jul 15;11(7):e1005395. (PMID: 26177267)
PLoS Biol. 2007 Oct;5(10):e256. (PMID: 17880264)
Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002)
BMC Genomics. 2013 Oct 10;14:695. (PMID: 24112604)
Nat Rev Microbiol. 2017 Feb;15(2):96-108. (PMID: 27867199)
Mol Cell Biol. 2009 Aug;29(16):4406-16. (PMID: 19528234)
Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792)
Mol Cell Biol. 2015 Nov 23;36(3):475-87. (PMID: 26598606)
Sci Signal. 2014 Feb 25;7(314):ra21. (PMID: 24570489)
Cold Spring Harb Perspect Med. 2014 Nov 10;5(8):a019794. (PMID: 25384771)
EMBO J. 1997 Apr 15;16(8):1982-91. (PMID: 9155024)
Mol Cell Biol. 2002 Jul;22(13):4739-49. (PMID: 12052881)
Bioinformatics. 2004 Nov 22;20(17):3246-8. (PMID: 15180930)
EMBO J. 2007 Aug 8;26(15):3521-33. (PMID: 17627274)
Mol Biol Cell. 2009 Jul;20(13):3101-14. (PMID: 19439450)
Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4880-5. (PMID: 18339808)
PLoS Pathog. 2017 Sep 27;13(9):e1006589. (PMID: 28953979)
PLoS Pathog. 2013 Mar;9(3):e1003210. (PMID: 23505370)
Infect Immun. 1998 Aug;66(8):3867-73. (PMID: 9673274)
Curr Opin Struct Biol. 2011 Oct;21(5):590-6. (PMID: 21889329)
J Bacteriol. 1998 Apr;180(7):1786-92. (PMID: 9537376)
Plant Cell. 2011 Mar;23(3):1171-85. (PMID: 21441438)
Biochim Biophys Acta. 2015 Jun;1849(6):722-30. (PMID: 25689021)
BMC Bioinformatics. 2011 Aug 04;12:323. (PMID: 21816040)
Yeast. 1994 Apr;10(4):425-39. (PMID: 7941729)
PLoS Biol. 2013 Jul;11(7):e1001614. (PMID: 23935449)
Dis Chest. 1956 Jun;29(6):649-68. (PMID: 13317782)
Mol Microbiol. 2016 May;100(3):425-41. (PMID: 26749104)
J Theor Biol. 2009 May 7;258(1):71-88. (PMID: 19490874)
Biotechniques. 2010 Jun;48(6):463-5. (PMID: 20569222)
Mol Biol Cell. 2003 Jun;14(6):2314-26. (PMID: 12808032)
Yeast. 1992 Apr;8(4):315-23. (PMID: 1514328)
Infect Immun. 2013 Feb;81(2):411-20. (PMID: 23184522)
PLoS Comput Biol. 2011 Oct;7(10):e1002195. (PMID: 22039361)
Mol Microbiol. 2003 Jan;47(1):89-102. (PMID: 12492856)
Eukaryot Cell. 2013 Jun;12(6):828-52. (PMID: 23563482)
PLoS Pathog. 2018 Nov 19;14(11):e1007444. (PMID: 30452484)
Eukaryot Cell. 2002 Apr;1(2):249-56. (PMID: 12455959)
PLoS One. 2013;8(3):e58613. (PMID: 23516516)
Genome Biol Evol. 2014 Dec 24;7(2):410-30. (PMID: 25539722)
Mol Microbiol. 1998 Feb;27(3):531-9. (PMID: 9489665)
Science. 2006 Apr 28;312(5773):583-8. (PMID: 16645097)
EMBO Rep. 2019 Jan;20(1):. (PMID: 30552148)
Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
PLoS One. 2010 Mar 10;5(3):e9490. (PMID: 20224823)
J Med Vet Mycol. 1988 Jun;26(3):137-43. (PMID: 3171821)
Eukaryot Cell. 2013 Sep;12(9):1214-24. (PMID: 23851338)
Genes Dev. 2004 Jul 15;18(14):1695-708. (PMID: 15256499)
Eukaryot Cell. 2009 Aug;8(8):1235-49. (PMID: 19542310)
Plant Cell Physiol. 2006 Jun;47(6):793-8. (PMID: 16608866)
Curr Genet. 1994 Dec;27(1):62-9. (PMID: 7750148)
Infect Immun. 2014 Oct;82(10):4414-25. (PMID: 25114108)
Stat Appl Genet Mol Biol. 2004;3:Article3. (PMID: 16646809)
Plant Cell. 2010 Jun;22(6):2085-101. (PMID: 20587773)
Genes Dev. 1992 Sep;6(9):1770-82. (PMID: 1516832)
Gene. 2001 Sep 5;275(1):107-14. (PMID: 11574158)
Mol Microbiol. 2013 Oct;90(1):22-35. (PMID: 23855748)
J Cell Biol. 2008 Jun 30;181(7):1073-81. (PMID: 18591427)
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14573-8. (PMID: 18791067)
G3 (Bethesda). 2017 Nov 6;7(11):3797-3808. (PMID: 28951491)
J Bacteriol. 2001 Jul;183(13):4090-3. (PMID: 11395474) - Grant Information: T32 AI007334 United States AI NIAID NIH HHS; United States HHMI Howard Hughes Medical Institute; R37 AI066224 United States AI NIAID NIH HHS; R01 AI137418 United States AI NIAID NIH HHS; R00 AI112691 United States AI NIAID NIH HHS; R01 AI066224 United States AI NIAID NIH HHS; R01 AI136735 United States AI NIAID NIH HHS; T32 AI060537 United States AI NIAID NIH HHS
- Accession Number: 0 (Fungal Proteins)
0 (Mucins)
EC 2.7.11.24 (Mitogen-Activated Protein Kinases) - Publication Date: Date Created: 20191001 Date Completed: 20200205 Latest Revision: 20230321
- Publication Date: 20240105
- Accession Number: PMC6786654
- Accession Number: 10.1371/journal.pbio.3000168
- Accession Number: 31568523
- Source:
Contact CCPL
Copyright 2022 Charleston County Public Library Powered By EBSCO Stacks 3.3.0 [350.3] | Staff Login
No Comments.