Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance

mBio - Tập 6 Số 4 - 2015
Iuliana V. Ene1, Louise A. Walker1, Marion Schiavone2,3,4,5, Keunsook K. Lee1, Hélène Martin‐Yken2,3,4,5, Étienne Dague6,7, Neil A. R. Gow1, Carol A. Munro1, Alistair J. P. Brown1
1School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom
2CNRS, UMR5504, Toulouse, France
3INRA, UMR792, Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France
4INSA,UPS,INP
5Université de Toulouse, INSA, UPS, INP, LISBP; Toulouse, France
6CNRS, LAAS, Toulouse, France
7Université de Toulouse, LAAS, Toulouse, France

Tóm tắt

ABSTRACT The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock. IMPORTANCE The C. albicans cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antifungal therapy. Its tensile strength is conferred by a network of cell wall polysaccharides, which are remodeled in response to growth conditions and environmental stress. However, little is known about how cell wall elasticity is regulated and how it affects adaptation to stresses such as sudden changes in osmolarity. We show that elasticity is critical for survival under conditions of osmotic shock, before stress signaling pathways have time to induce gene expression and drive glycerol accumulation. Critical cell wall remodeling enzymes control cell wall flexibility, and its regulation is strongly dependent on host nutritional inputs. We also demonstrate an entirely new level of cell wall dynamism, where significant architectural changes and structural realignment occur within seconds of an osmotic shock.

Từ khóa


Tài liệu tham khảo

10.1128/MCB.15.2.601

10.1074/jbc.275.20.14882

10.1091/mbc.E08-11-1155

10.1099/00221287-136-7-1421

10.1172/JCI27114

10.1016/j.mib.2012.04.005

10.1371/journal.ppat.1004050

10.1146/annurev.bi.51.070182.003555

10.1054/drup.2001.0185

10.1128/EC.3.4.955-965.2004

10.1002/bies.20441

10.1016/B978-0-12-407678-5.00004-0

10.3109/10408418709104445

10.1002/yea.320100702

10.1046/j.1365-2958.2000.01729.x

10.3109/1040841X.2013.813904

10.1016/S0008-6215(03)00169-1

10.1002/yea.1007

10.1046/j.1365-2958.2000.01944.x

10.1074/jbc.M502162200

10.1074/jbc.M411413200

10.1074/jbc.M510360200

10.1111/j.1567-1364.2009.00541.x

Munro CA, Richard ML. 2012. The cell wall: glycoproteins, remodeling and regulation, p 197–223. In Calderone RA, Clancy CJ (ed), Candida and candidiasis, 2nd ed. ASM Press, Washington, DC.

10.1080/mmy.39.1.41.53

10.1074/jbc.272.28.17762

10.1046/j.1365-2958.2001.02347.x

10.1002/yea.1473

10.1128/EC.00228-09

10.1128/JB.181.22.7070-7079.1999

10.1002/yea.1061

10.1074/jbc.M606361200

10.1093/nar/gkn663

Cabib E, Bowers B, Sburlati A, Silverman SJ. 1988. Fungal cell wall synthesis: the construction of a biological structure. Microbiol Sci 5:370–375.

10.1128/EC.00085-13

10.1080/mmy.39.1.1.8-0

10.1371/journal.ppat.1000040

10.1074/mcp.M200062-MCP200

10.1099/mic.0.2007/012617-0

10.1128/IAI.01092-12

10.1128/EC.00278-12

10.1002/pmic.200390046

10.1128/AAC.49.6.2226-2236.2005

10.1016/j.fgb.2008.08.003

10.1128/MMBR.66.2.300-372.2002

10.1038/nbt1114

10.1099/00221287-132-7-2023

10.1007/s002030000136

10.1007/s00249-010-0612-0

10.1128/jb.178.19.5850-5852.1996

10.1091/mbc.E04-03-0181

10.1099/mic.0.28040-0

10.1099/mic.0.28038-0

10.1126/scisignal.2000056

10.1099/00221287-144-2-411

10.1099/mic.0.28616-0

10.1128/EC.00081-09

10.1111/j.1462-5822.2012.01813.x

10.1099/mic.0.27723-0

10.1128/MCB.25.23.10611-10627.2005

10.1186/1756-0500-5-258

10.1128/MCB.15.4.2197

10.1128/AAC.41.11.2471

10.1099/mic.0.27220-0

10.1016/j.resmic.2005.05.002

10.1046/j.1365-2958.2003.03495.x

10.1128/IAI.72.12.7330-7333.2004

10.1111/j.1365-2958.2005.05037.x

10.1128/mr.43.2.117-144.1979

10.1016/B978-0-12-335845-5.50004-5

10.1099/mic.0.044206-0

10.1002/pmic.201200228

10.1016/S0008-6215(00)00105-1

10.1016/j.carres.2004.05.033

10.1128/JB.181.10.3058-3068.1999

10.1091/mbc.E07-06-0581

10.1091/mbc.E12-06-0477

Odds FC, Webster CE, Mayuranathan P, Simmons PD. 1988. Candida and candidosis. Bailliere Tindall, London, United Kingdom.

10.1128/9781555817176

10.1128/iai.63.11.4528-4530.1995

10.1128/IAI.66.7.3317-3325.1998

10.1371/journal.pone.0045912

10.1002/1097-0061(20000315)16:4<325::AID-YEA538>3.0.CO;2-#

10.1088/0957-4484/22/39/395102

10.1002/yea.1801

10.1038/nprot.2015.004

10.1063/1.1143970

10.1093/genetics/134.3.717

10.1099/00221287-143-2-297

10.1128/JB.181.6.1868-1874.1999

10.1128/IAI.68.10.5953-5959.2000

10.1128/EC.4.2.298-309.2005

10.1016/j.fgb.2005.05.006

10.1128/IAI.66.6.2713-2721.1998

10.1099/00221287-144-2-425

10.1128/EC.3.5.1111-1123.2004

10.1128/JB.180.15.3809-3815.1998

10.1128/MCB.17.10.5960

10.1371/journal.pgen.1000783

Thông tin
Thông tin xuất bản

mBio

Tập 6 Số 4

Thông tin tác giả