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PNAS 102 (15): 5576-5581

Copyright © 2005 by the National Academy of Sciences.


A contact-activated kinase signals Candida albicans invasive growth and biofilm development

Carol A. Kumamoto *

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111

Edited by Gerald R. Fink, Whitehead Institute for Biomedical Research, Cambridge, MA, and approved March 7, 2005

Received for publication September 24, 2004.

Abstract: For mammalian cells, contact-dependent regulatory controls are crucially important for controlling cellular proliferation and preventing diseases such as cancer. Candida albicans, an opportunistic fungal pathogen that normally resides within a mammalian host, also exhibits contact-dependent cellular behaviors such as invasive hyphal growth and biofilm development. Results reported here demonstrate that, in C. albicans, physical contact results in activation of the mitogen-activated protein kinase Mkc1p. This kinase is part of the fungal cell integrity pathway, a signal transduction pathway known to be activated by cell wall stress. It is demonstrated here that Mkc1p is required for invasive hyphal growth and normal biofilm development. Therefore, Mkc1p signaling contributes to contact-dependent regulation. Because responding to contact appropriately allows coordinated cellular behavior in a metazoan, commensal C. albicans cells behave like a part of the host, using contact-activated signaling to regulate fungal behavior.

Key Words: cell integrity pathway • mitogen-activated protein kinase • hyphae

Author contributions: C.K. designed research, performed research, analyzed data, and wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: MAP, mitogen-activated protein; HA, hemagglutinin; YPD, yeast extract/peptone/dextrose; YPS, yeast extract/peptone/sucrose; SD medium, synthetic defined medium; CM, complete medium; log phase, logarithmic phase; CLSI, Clinical and Laboratory Standards Institute; XTT, [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide].

* E-mail: carol.kumamoto{at}

© 2005 by The National Academy of Sciences of the USA

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