title: SR-like RNA-binding protein Slr1 affects Candida albicans filamentation and virulence.
abstract: Candida albicans causes both mucosal and disseminated infections, and its capacity to grow as both yeast and hyphae is a key virulence factor. Hyphal formation is a type of polarized growth, and members of the SR (serine-arginine) family of RNA-binding proteins influence polarized growth of both Saccharomyces cerevisiae and Aspergillus nidulans. Therefore, we investigated whether SR-like proteins affect filamentous growth and virulence of C. albicans. BLAST searches with S. cerevisiae SR-like protein Npl3 (ScNpl3) identified two C. albicans proteins: CaNpl3, an apparent ScNpl3 ortholog, and Slr1, another SR-like RNA-binding protein with no close S. cerevisiae ortholog. Whereas ScNpl3 was critical for growth, deletion of NPL3 in C. albicans resulted in few phenotypic changes. In contrast, the slr1Δ/Δ mutant had a reduced growth rate in vitro, decreased filamentation, and impaired capacity to damage epithelial and endothelial cells in vitro. Mice infected intravenously with the slr1Δ/Δ mutant strain had significantly prolonged survival compared to that of mice infected with the wild-type or slr1Δ/Δ mutant complemented with SLR1 (slr1Δ/Δ+SLR1) strain, without a concomitant decrease in kidney fungal burden. Histopathology, however, revealed differential localization of slr1Δ/Δ hyphal and yeast morphologies within the kidney. Mice infected with slr1Δ/Δ cells also had an increased brain fungal burden, which correlated with increased invasion of brain, but not umbilical vein, endothelial cells in vitro. The enhanced brain endothelial cell invasion was likely due to the increased surface exposure of the Als3 adhesin on slr1Δ/Δ cells. Our results indicate that Slr1 is an SR-like protein that influences C. albicans growth, filamentation, host cell interactions, and virulence.
authors: Department of Biology, Bowdoin College, Brunswick, Maine, USA.
authors: Chaiyaboot
authors: C
authors: Ariyachet
authors: Norma V
authors: NV
authors: Solis
authors: Yaoping
authors: Y
authors: Liu
authors: Nemani V
authors: NV
authors: Prasadarao
authors: Scott G
authors: SG
authors: Filler
authors: Anne E
authors: AE
authors: McBride
mesh_terms: D000818:Animals; D001921:Brain / Q000382:microbiology; D002176:Candida albicans / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D025301:Hyphae / Q000166:cytology / Q000254:growth & development / Q000472:pathogenicity; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016019:Survival Analysis; D014774:Virulence
chemical_list: D016601:RNA-Binding Proteins
references: Genetics. 2010 Jun;185(2):513-22
references: 20382833
references: Eukaryot Cell. 2007 Jul;6(7):1119-29
references: 17483287
references: Wiley Interdiscip Rev RNA. 2011 May-Jun;2(3):408-16
references: 21957026
references: Science. 1994 Dec 9;266(5191):1723-6
references: 7992058
references: PLoS Pathog. 2006 Dec;2(12):e129
references: 17196036
references: Infect Immun. 1998 Nov;66(11):5301-6
references: 9784536
references: Annu Rev Microbiol. 2007;61:529-53
references: 17506678
references: Eukaryot Cell. 2008 Apr;7(4):712-20
references: 18281602
references: Mol Microbiol. 2011 May;80(4):995-1013
references: 21414038
references: Mol Biol Cell. 1992 Aug;3(8):875-93
references: 1392078
references: Nucleic Acids Res. 1999 Jul 1;27(13):2618-26
references: 10373577
references: Cell Microbiol. 2005 Apr;7(4):499-510
references: 15760450
references: J Bacteriol. 1999 Mar;181(6):1868-74
references: 10074081
references: EMBO J. 2005 Jun 15;24(12):2150-60
references: 15902270
references: Trends Genet. 2008 Dec;24(12):590-4
references: 18992956
references: Mol Microbiol. 2011 Feb;79(4):968-89
references: 21299651
references: Antimicrob Agents Chemother. 2001 Nov;45(11):3195-7
references: 11600377
references: PLoS Biol. 2007 Mar;5(3):e64
references: 17311474
references: PLoS Genet. 2010 Aug 19;6(8):e1001070
references: 20808890
references: Biochem J. 2009 Jan 1;417(1):15-27
references: 19061484
references: Infect Immun. 2000 Oct;68(10):5953-9
references: 10992507
references: RNA. 2001 Feb;7(2):302-13
references: 11233987
references: Genetics. 1997 Mar;145(3):671-84
references: 9055077
references: Mol Biol Cell. 2005 Jun;16(6):2903-12
references: 15814840
references: PLoS Pathog. 2011 Oct;7(10):e1002305
references: 21998592
references: Genome Biol. 2009;10(10):242
references: 19857271
references: PLoS Genet. 2009 Sep;5(9):e1000664
references: 19779551
references: FEMS Microbiol Rev. 2007 Apr;31(3):327-41
references: 17298585
references: Mol Biol Cell. 2002 Oct;13(10):3452-65
references: 12388749
references: Mol Biol Cell. 2001 Jul;12(7):2147-70
references: 11452010
references: Infect Immun. 1999 Oct;67(10):5522-5
references: 10496943
references: PLoS One. 2008 Sep 26;3(9):e3273
references: 18818768
references: Cell Microbiol. 2010 Mar;12(3):273-82
references: 19919567
references: Genes Dev. 1996 May 15;10(10):1233-46
references: 8675010
references: Mol Cell Biol. 2004 Dec;24(23):10479-91
references: 15542855
references: PLoS Genet. 2009 Mar;5(3):e1000400
references: 19266018
references: Curr Opin Microbiol. 2010 Dec;13(6):693-9
references: 20880737
references: Traffic. 2010 Dec;11(12):1498-505
references: 21040295
references: Eukaryot Cell. 2003 Oct;2(5):1053-60
references: 14555488
references: Cell. 1997 Sep 5;90(5):939-49
references: 9298905
references: Fungal Genet Biol. 2005 Oct;42(10):862-72
references: 16098776
references: Mol Cell. 2009 Jul 10;35(1):1-10
references: 19595711
references: J Cell Biol. 1992 Nov;119(4):737-47
references: 1429834
references: J Clin Invest. 1973 Nov;52(11):2745-56
references: 4355998
references: J Cell Biol. 1994 Aug;126(3):649-59
references: 8045930
references: Infect Immun. 2004 Jan;72(1):598-601
references: 14688143
references: Eukaryot Cell. 2005 Aug;4(8):1493-502
references: 16087754
references: Mol Cell. 2008 Dec 5;32(5):727-34
references: 19061647
references: Clin Infect Dis. 2004 Aug 1;39(3):309-17
references: 15306996
references: Infect Immun. 2000 Jun;68(6):3485-90
references: 10816502
references: J Biol Chem. 2005 Mar 18;280(11):10455-61
references: 15632157
references: Genome Res. 2010 Oct;20(10):1451-8
references: 20810668
references: Nat Genet. 2010 Jul;42(7):590-8
references: 20543849
references: Genome Biol. 2010;11(7):R71
references: 20618945
references: Nat Protoc. 2012 Mar 08;7(4):637-42
references: 22402633
references: FEMS Microbiol Lett. 2004 Jun 15;235(2):297-303
references: 15183877
references: J Cell Biol. 2000 Aug 21;150(4):707-18
references: 10952997
references: Microbes Infect. 2010 Jun;12(6):488-96
references: 20223293
references: Appl Environ Microbiol. 1990 Jun;56(6):1875-81
references: 16348228