Previous Article | Next Article 
Journal of Bacteriology, December 1999, p. 7243-7247, Vol. 181, No. 23
Department of Hygiene,
Received 26 April 1999/Accepted 22 September 1999
The pathogenic fungus Candida albicans harbors three
histidine kinase genes called CaSLN1, CaNIK1,
and CaHK1. The disruption of any one of these three genes
impaired the hyphal formation and attenuated the virulence of C. albicans in a mouse systemic candidiasis model. The effects of
the disruption on hyphal formation and virulence were most severe in
the cahk1 As in bacteria, eukaryotic cells
harbor a histidine kinase osmosensing mechanism to adapt to osmotic
changes. Sln1p of the yeast Saccharomyces cerevisiae is one
of a family of two-component regulators and carries both histidine
kinase and response regulator domains (14, 18). Under normal
conditions (low osmolarity), Sln1p autophosphorylates a specific
histidine in the kinase domain. The phosphate moiety on this histidine
is transferred to a certain aspartic acid in the response regulator
domain, then to Ypd1p, and further to Ssk1p to keep Hog1p
mitogen-activated protein (MAP) kinase activity turned off
(4, 14, 19). Under high-osmolarity conditions, the
autokinase activity of ScSln1p is turned off, which leads to the
activation of Hog1p MAP kinase and the transcription of a family of
osmoresponse genes, including that of glycerol phosphate dehydrogenase
(GPD1) (1, 4, 14, 19). Besides affecting the MAP
kinase cascade, the activity of Sln7p, which mediates oxidative stress
and is required for MCM1-dependent gene expression, is also regulated
by a phosphorelay from Ypd1p (13). Because a mutation of
either the phosphorylating histidine or the receiver aspartic acid of
Sln1p is lethal, the phosphorelay from Sln1p is essential for the
growth of S. cerevisiae at low osmolarity (14).
Unlike S. cerevisiae, the pathogenic fungus Candida
albicans harbors three putative histidine kinase genes called
CaSLN1, CaNIK1, and CaHK1 (3, 6,
16, 22). Although CaSLN1 functionally complements an
S. cerevisiae sln1 In this study, we generated single and double disruptants of the
C. albicans histidine kinase genes and showed that every histidine kinase is involved in hyphal formation and virulence. In
addition, we hypothesize that CaSLN1 and CaNIK1
function upstream of CaHK1 but are located in distinct
signal transmission pathways.
Screening of the C. albicans HK1 gene.
The
CaHK1 gene was cloned by screening a C. albicans
genomic DNA library with the 1.5-kb XbaI-XbaI
fragment of CaHK1 as a probe, which was amplified by PCR.
Hybridization was carried out under low-stringency conditions in a
buffer containing 0.25 M sodium phosphate (pH 7.2), 2× SSC (1× SSC
contains 150 mM NaCl and 15 mM sodium citrate), 1% (wt/vol) bovine
serum albumin, 1 mM EDTA, 0.1% (wt/vol) sodium dodecyl sulfate (SDS),
and 25% (vol/vol) formamide at 37°C. Radiolabelling of DNA with
[ Disruption of CaNIK1 and CaHK1.
Disruption
of the histidine kinase genes was performed according to the
ura-blaster protocol (9). The entire open reading frames of
CaSLN1, CaNIK1, and CaHK1 were cloned
into pUC19. Then, the 0.6-kb SnaBI-BalI region of
CaSLN1 (16), the 1.4-kb
BalI-BalI region of CaNIK1, and the
3.5-kb HpaI-BstPI region of CaHK1 were excised and ligated with a 3.8-kb BamHI-XbaI
fragment carrying the hisG-URA3-hisG module (9),
generating pCASLN1U, pCANIK1U, and pCAHK1U. After the three constructs
were linearized by digestion with an appropriate endonuclease, 10 µg
of each was transformed into C. albicans CAI4
(ura3 Determination of virulence.
Four-week-old male CD-1 mice
were purchased from Charles River Japan (Tokyo, Japan) and were
intravenously injected with 107 cells of C. albicans strains as indicated below. The number of surviving mice
was scored.
Expression of the recombinant CaSln1, CaNik1, and CaHk1
proteins.
The entire coding region of the glutathione
S-transferase (GST) gene was cloned between the
BamHI and HindIII sites (downstream of the
polyhedrin promoter) of pFASTBAC1 with the BamHI and
HindIII linkers to generate pFASTBAC1-GST. The DNA
fragments encoding amino acids 417 to 1378 of CaSln1p, 421 to 1082 of
CaNik1p, and 1930 to 2472 of CaHk1p were amplified by PCR and ligated
at the HindIII site of pFASTBAC1-GST. Thus,
CaSln1p(417-1378), CaNik1p(421-1082), and CaHk1p(1930-2472) were
expressed in insect cells as fusions with GST. Insect cells (Sf-9) were
infected with baculoviruses bearing CaSLN1,
CaNIK1, or CaHK1 at a multiplicity of infection of 10 and further cultured for 72 h (15). The GST
fusion proteins, designated GST-CaSln1p, GST-CaNik1p, and GST-CaHk1p,
respectively, were extracted from the infected cells and purified by
affinity column chromatography with glutathione-Sepharose as previously described (24). For Western blotting, approximately 0.1-µg
quantities of the proteins were separated on SDS-polyacrylamide gels,
hybridized with anti-GST antibody (Pharmacia), and detected with the
ECL-plus kit (Amersham).
Assays for autophosphorylation activities of the recombinant
CaSln1, CaNik1, and CaHk1 proteins.
Autophosphorylation activities
of the C. albicans histidine kinases were determined by
incubating approximately 10 µg of the purified proteins that were
bound to glutathione-conjugated agarose beads in a buffer containing 50 mM Tris-HCl (pH 7.5), 50 mM KCl, 5 mM MgCl2, 2 mM
dithiothreitol, and 20 µM [ To gain more insight into the physiological roles of the C. albicans histidine kinases, we generated and characterized a
series of mutant strains in which one or two histidine kinase genes
were disrupted. Disruption constructs were designed to eliminate the autokinase domains of CaSln1p (16) and the autokinase and
receiver domains of CaNik1p and CaHk1p (Fig.
1). All the mutants used for the
experiments contained one copy of URA3 (Table 1) and
exhibited similar doubling times (ranging from 1.5 to 2 h) when
cultured in YPD medium.
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Roles of Three Histidine Kinase Genes in Hyphal
Development and Virulence of the Pathogenic Fungus Candida
albicans
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
null mutants. Although the double disruption
of CaSLN1 and CaNIK1 was impossible, further deletion of CaSLN1 or CaNIK1 in the
cahk1 null mutants partially restored the serum-induced
hypha-forming ability and virulence. When incubated with radiolabelled
ATP, the recombinant CaSln1 and CaNik1 proteins, which contained their
own kinase and response regulator domains, were autophosphorylated,
whereas CaHk1p was not. These results imply that in C. albicans, CaSLN1 and CaNIK1 function
upstream of CaHK1 but are in distinct signal transmission pathways.
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
mutation, disruption of
SLN1 in C. albicans does not alter viability and
only slightly affects the tolerance of osmotic stresses
(16). CaNIK1 is the C. albicans homolog of the Neurospora crassa NIK1 gene, which has been
shown to be required for osmotolerance (2). The deletion of
NIK1 in C. albicans, however, caused a defect in
hyphal formation (3) and reduced the efficiency of
high-frequency phenotypic switching (22). Recently, Calera
et al. demonstrated that a null mutation of CaHK1 induced
flocculation under certain conditions and affected the virulence, and
they suggested that CaHK1 modulates the expression of cell
surface components (5, 7).
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
-32P]dCTP and DNA sequencing were carried out by a
random priming method as previously described (20).
Construction of the C. albicans genomic DNA library and
cloning of CaSLN1 and CaNIK1 were reported
previously (16, 24).
::imm434/ura3::imm434)
cells by the lithium acetate method (21), and the
integration of the hisG-URA3-hisG module into the targeting
alleles was confirmed by PCR and Southern blotting. After the
URA3 gene was excised by 5-fluoroortic acid (5-FOA), the
heterozygous mutants were again transformed with the same disruption
constructs and selected by ura auxotrophs. Double disruptants were
created by further disrupting the CaNIK1 or CaHK1
alleles in the casln1 null mutants. All the mutants used
for the experiments contained one copy of URA3 at a
disrupted histidine kinase locus (Table
1). Unless otherwise specified, C. albicans cells were cultured in YPD (1% [wt/vol] yeast extract, 2% [wt/vol] peptone, 2% [wt/vol] dextrose). Hyphal formation was induced by culturing the C. albicans cells on agar plates
containing 10% fetal bovine serum at 37°C for 3 days.
TABLE 1.
Histidine kinase mutants of C. albicans used
in this study
-32P]ATP (specific
activity, 100 Ci/mmol) at 37°C for 30 min. After incubation, the
proteins were separated on SDS-7.5% polyacrylamide gels and
visualized by autoradiography (19).
RESULTS AND DISCUSSION
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
View larger version (28K):
[in a new window]
FIG. 1.
Disruption of CaSLN1, CaNIK1, and
CaHK1 in C. albicans. The strategy for disrupting
each histidine kinase gene is illustrated with the expected structure
of each product. The entire open reading frames of CaSLN1,
CaNIK1, and CaHK1 were cloned into pUC19. Then,
the 0.6-kb SnaBI-BalI region of CaSLN1
(16), the 1.4-kb BalI-BalI region of
CaNIK1, and the 3.5-kb HpaI-BstPI
region of CaHK1 were replaced by the
hisG-URA3-hisG module (9). H519 and
D1304 of CaSln1p, H510 and D924 of
CaNik1P, and H2007 and D2394 of CaHk1p are the
predicted phosphorylating histidines and aspartic acids, respectively,
of their products. TM, transmembrane domain; HK, histidine kinase
domain; REC, response receiver domain; WD-REP, repeats of an
approximately 90-amino-acid motif; S/T-K like, serine/threonine
kinase-like domain; aa, amino acids.
Because a null mutation of CaNIK1 was shown to cause a
severe defect in hyphal formation in spider medium (3),
these disruptants were first tested for the ability to develop hyphae.
We used serum to induce hyphal growth because, among tested substances,
serum was the most effective inducer of hyphal growth of CAF2-1 and its
histidine kinase mutants. Consistent with the previous report by Alex
et al. (3), hyphal formation was significantly deteriorated in the canik1 null mutants, even when hyphal development
was induced by serum (Fig. 2). Disruption
of CaSLN1 or CaHK1 also impaired hyphal formation
compared with that of the wild type, CAF2-1 (Fig. 2). Effects of the
disruption of a histidine kinase gene on hyphal formation were more
prominent in cahk1 null mutants. The hypha-forming
ability was nearly completely abolished in the cahk1 null
mutants, whereas the casln1 and canik1 null
mutants inefficiently generated hyphae on the periphery of the colonies when they were cultured in the presence of serum (Fig. 2A).
|
CaSln1p is predicted to be a cell surface protein with an extracellular
sensor domain, whereas both CaNik1p and CaHk1p are supposed to be
cytosolic proteins (Fig. 1) (3, 6, 16, 22). Therefore, we
asked if CaSln1p functions upstream of CaNik1p and CaHk1p. To address
this possibility, we created mutants in which more than one histidine
kinase gene was disrupted. Double disruption of CaSLN1 and
CaNIK1 was impossible, suggesting that a simultaneous
disruption of CaSLN1 and CaNIK1 is lethal. The disruption of CaSLN1 or CaNIK1 in the
cahk1 null mutants partially restored hypha-forming
ability in the presence of serum. Both casln1
cahk1 null mutants and canik1
cahk1 null mutants developed hyphae more efficiently than
did cahk1 null mutants (Fig. 2). These results suggest
that CaSLN1 and CaNIK1 are located upstream of
CaHK1 but function in distinct signal transmission pathways. Furthermore, because both CaSLN1 and CaNIK1 are
required for hyphal formation, there may be a negative regulator
between CaHk1p and the other two histidine kinases.
The hypha-forming ability of C. albicans has been thought to
be related to virulence (17). This prompted us to examine
the effects that a deletion of the histidine kinase genes would have on
virulence in a mouse systemic candidiasis model. Immunocompetent CD-1
mice were intravenously injected with 107 cells of each
mutant, and their survival was monitored. As shown in Fig.
3, all mice that were injected with
wild-type CAF2-1 cells died within 5 days. The virulence of the
cahk1 null mutants was markedly reduced, whereas that of
the casln1 null mutants and canik1 null
mutants was only slightly attenuated compared with that of CAF2-1 (Fig.
3). In addition, the deletion of CaSLN1 or CaNIK1
in the cahk1 null mutants partially restored the
virulence. The restoration of the virulence by the deletion of
CaSLN1 or CaNIK1 in the cahk1
background also coincided with the reappearance of hypha-forming
ability in the presence of serum. These results also support our
hypothesis that CaSln1p and CaNik1p are located upstream of CaHk1p,
regulating negative effectors of CaHk1p. Although Lay et al. reported
the positional effects of URA3 on orotidine 5'-monophosphate
decarboxylase activity (12) and virulence, we did not see a
clear correlation between the orotidine 5'-monophosphate decarboxylase
activities of the histidine kinase mutants and their virulence.
|
CaSln1p, CaNik1p, and CaHk1p all possess histidine kinase domains, but
their enzyme activities remain to be established. To confirm the kinase
activities of these proteins, we expressed the truncated forms of
CaSln1p, CaNik1p, and CaHk1p, which contain their own putative
autokinase and response receiver domains. The recombinant proteins were
expressed as GST fusion proteins in insect cells and purified by
affinity chromatography with glutathione-Sepharose CL-4B (Fig.
4). Upon incubation with
[-32P]ATP, both GST-CaSln1p and GST-CaNik1p were
strongly labelled with 32P, whereas no radioactivity was
detected on GST or GST-CaHk1p (Fig. 4). Although we cannot rule out the
possibility that GST-CaHk1p was not expressed in a correct conformation
to sustain the activity, the above result suggests that at least
CaSln1p and CaNik1p utilize their autokinase activities to initiate the
phosphorelay in vivo.
|
Several histidine kinase genes in eukaryotes were identified, and they
are presumably involved in signal transmission, e.g., sensing and
adapting to changes of osmolarity in S. cerevisiae (14) and N. crassa (2) and ethylene
sensing in plants (8, 10, 23). In this study, we have shown
that the histidine kinases are involved in serum-induced hyphal
development and virulence in C. albicans, but the real
inducer for signal transmission remains to be identified. As mentioned
above, Hog1p and Skn7p sense the signal from Sln1p and control the
expression of the downstream genes (13, 14). In addition, it
has been demonstrated that the activation of Hog1p is associated with
the tyrosine phosphorylation of the protein (4, 14). We also
created an anti-Hog1p antibody to see whether the tyrosine
phosphorylation on Hog1p is induced during hyphal induction and whether
it is altered in the mutants with disruptions of the histidine kinase
genes. Detection of the tyrosine phosphorylation of Hog1p upon hyphal
induction and increased osmolarity, however, was unsuccessful,
presumably due to strong phosphatase activities within the C. albicans cells. In addition, the hypha-forming ability and
virulence of the hog1 null mutants were not affected by
the further disruption of any histidine kinase gene in the
hog1 null mutants. Furthermore, whereas the
hog1 null mutants displayed increased susceptibilities to
a wide variety of stresses, such as hyperosmolarity (11),
higher temperature, anisomycin, and arsenite, none of the histidine
kinase mutants showed retarded growth under these conditions compared
with the growth of the wild type, CAF2-1. Thus, it seems that
CaSLN1, CaNIK1, and CaHK1 are all
independent of HOG1 in C. albicans.
| |
ACKNOWLEDGMENTS |
|---|
We thank S. B. Miwa for reading the manuscript.
This work was supported in part by a grant from the Ministry of Education, Science and Culture, Japan, to T.Y.-O.
T.Y.-O. and T.M. contributed equally to this study.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan. Phone: 81-467-45-4382. Fax: 81-467-46-5320. E-mail: hisafumi.okabe{at}roche.com.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
|
|---|
| 1. |
Albertyn, J.,
S. Hohmann,
J. M. Thevelein, and B. A. Prior.
1994.
GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway.
Mol. Cell. Biol.
14:4135-4144 |
| 2. |
Alex, L. A.,
K. A. Borkovich, and M. I. Simon.
1996.
Hyphal development in Neurospora crassa: involvement of a two-component histidine kinase.
Proc. Natl. Acad. Sci. USA
93:3416-3421 |
| 3. |
Alex, L. A.,
C. Korch,
C. P. Selitrennikoff, and M. I. Simon.
1998.
COS1, a two component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans.
Proc. Natl. Acad. Sci. USA
95:7069-7073 |
| 4. |
Brewster, J. L.,
T. de Valoir,
D. Dwyer,
E. Winter, and M. C. Gustin.
1993.
An osmosensing signal transduction pathway in yeast.
Science
259:1760-1763 |
| 5. |
Calera, J. A., and R. Calderone.
1999.
Flocculation of hyphae is associated with a deletion in the putative CaHK1 two-component histidine kinase gene from Candida albicans.
Microbiology
145:1431-1442 |
| 6. | Calera, J. A., G. H. Choi, and R. A. Calderone. 1998. Identification of a putative histidine kinase two-component phosphorelay gene (CaHK1) in Candida albicans. Yeast 14:665-674[Medline]. |
| 7. |
Calera, J. A.,
X.-J. Zhao,
F. De Bernardis,
M. Sheridan, and R. Calderone.
1999.
Avirulence of Candida albicans CaHK1 mutants in a murine model of hematogenously disseminated candidiasis.
Infect. Immun.
67:4280-4284 |
| 8. |
Chang, C.,
S. F. Kwok,
A. B. Bleecker, and E. M. Meyerowitz.
1993.
Arabidopsis ethylene-response gene ETR1: similarity of product to two component regulators.
Science
262:539-544 |
| 9. | Fonzi, W. A., and M. Y. Irwin. 1993. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134:717-728[Abstract]. |
| 10. |
Hua, J.,
C. Chang,
Q. Sun, and E. M. Meyerowitz.
1995.
Ethylene insensitivity conferred by Arabidopsis ERS gene.
Science
269:1712 |
| 11. |
Jose, C. S.,
R. A. Monge,
R. Perez-Diaz,
J. Pla, and C. Nombela.
1996.
The mitogen-activated protein kinase homolog HOG1 gene controls glycerol accumulation in the pathogenic fungus Candida albicans.
J. Bacteriol.
178:5850-5852 |
| 12. |
Lay, J.,
L. K. Henry,
J. Clifford,
Y. Koltin,
C. E. Bulawa, and J. M. Becker.
1998.
Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies.
Infect. Immun.
66:5301-5306 |
| 13. | Li, S., A. Ault, C. L. Malone, D. Raitt, S. Dean, L. H. Johnston, R. J. Deschenes, and J. S. Fassler. 1998. The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p. EMBO J. 17:6952-6962[Medline]. |
| 14. | Maeda, T., S. M. Wurgler-Murphy, and H. Saito. 1994. A two component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369:242-245[Medline]. |
| 15. | Murphy, C. I., H. Piwnica-Worms, S. Grunwald, and W. G. Romanow. 1997. Expression of proteins in insect cells using baculovirus vectors, p. 16.9.1-16.11.12. In F. M. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, and K. Struhl (ed.), Current protocols in molecular biology. John Wiley & Sons, Inc., New York, N.Y |
| 16. |
Nagahashi, S.,
T. Mio,
N. Ono,
T. Yamada-Okabe,
M. Arisawa,
H. Bussey, and H. Yamada-Okabe.
1998.
Isolation of CaSLN1 and CaNIK1, the genes for osmosensing histidine kinase homologues, from the pathogenic fungus Candida albicans.
Microbiology
144:425-432 |
| 17. | Odds, F. C. 1987. Candida infections: an overview. Crit. Rev. Microbiol. 15:1-5[Medline]. |
| 18. |
Ota, I. M., and A. Varshavsky.
1993.
A yeast protein similar to bacterial two component regulators.
Science
262:566-569 |
| 19. | Posas, F., S. M. Wurgler-Murphy, T. Maeda, E. Witten, T. C. Thai, and H. Saito. 1996. Yeast HOG1 MAP kinase cascade is regulated by a multiple phosphorylating mechanism in the SLN1-TPD1-SSK1 "two-component" osmosensor. Cell 86:865-875[Medline]. |
| 20. | Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y |
| 21. |
Sanglard, M.,
F. Ischer,
M. Monod, and J. Bille.
1997.
Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene.
Microbiology
143:405-416 |
| 22. |
Srikantha, T.,
L. Tsai,
K. Daniels,
L. Enger,
K. Highley, and D. R. Soll.
1998.
The two-component hybrid kinase regulator CaNIK1 of Candida albicans.
Microbiology
144:2715-2729 |
| 23. |
Wilkinson, J. Q.,
M. B. Lanahan,
H.-C. Yen,
J. J. Giovannoni, and H. J. Klee.
1995.
An ethylene-inducible component of signal transduction encoded by Never-ripe.
Science
270:1807-1809 |
| 24. |
Yamada-Okabe, T.,
O. Shimmi,
R. Doi,
K. Mizumoto,
M. Arisawa, and H. Yamada-Okabe.
1996.
Isolation of the mRNA-capping enzyme and ferric reductase related genes from Candida albicans.
Microbiology
142:2515-2523 |
Journal of Bacteriology, December 1999, p. 7243-7247, Vol. 181, No. 23
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Bahn, Y.-S.
(2008). Master and Commander in Fungal Pathogens: the Two-Component System and the HOG Signaling Pathway. Eukaryot Cell
7: 2017-2036
[Full Text] -
Chauhan, N., Calderone, R.
(2008). Two-Component Signal Transduction Proteins as Potential Drug Targets in Medically Important Fungi. Infect. Immun.
76: 4795-4803
[Full Text] -
Chapeland-Leclerc, F., Paccallet, P., Ruprich-Robert, G., Reboutier, D., Chastin, C., Papon, N.
(2007). Differential Involvement of Histidine Kinase Receptors in Pseudohyphal Development, Stress Adaptation, and Drug Sensitivity of the Opportunistic Yeast Candida lusitaniae. Eukaryot Cell
6: 1782-1794
[Abstract] [Full Text] -
Biswas, S., Van Dijck, P., Datta, A.
(2007). Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans. Microbiol. Mol. Biol. Rev.
71: 348-376
[Abstract] [Full Text] -
Bahn, Y.-S., Kojima, K., Cox, G. M., Heitman, J.
(2006). A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans. Mol. Biol. Cell
17: 3122-3135
[Abstract] [Full Text] -
Nickerson, K. W., Atkin, A. L., Hornby, J. M.
(2006). Quorum sensing in dimorphic fungi: farnesol and beyond.. Appl. Environ. Microbiol.
72: 3805-3813
[Full Text] -
Nemecek, J. C., Wuthrich, M., Klein, B. S.
(2006). Global control of dimorphism and virulence in fungi.. Science
312: 583-588
[Abstract] [Full Text] -
Monge, R. A., Roman, E., Nombela, C., Pla, J.
(2006). The MAP kinase signal transduction network in Candida albicans.. Microbiology
152: 905-912
[Abstract] [Full Text] -
Roman, E., Nombela, C., Pla, J.
(2005). The Sho1 Adaptor Protein Links Oxidative Stress to Morphogenesis and Cell Wall Biosynthesis in the Fungal Pathogen Candida albicans. Mol. Cell. Biol.
25: 10611-10627
[Abstract] [Full Text] -
Fan, W., Kraus, P. R., Boily, M.-J., Heitman, J.
(2005). Cryptococcus neoformans Gene Expression during Murine Macrophage Infection. Eukaryot Cell
4: 1420-1433
[Abstract] [Full Text] -
Arana, D. M., Nombela, C., Alonso-Monge, R., Pla, J.
(2005). The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans. Microbiology
151: 1033-1049
[Abstract] [Full Text] -
Du, C., Calderone, R., Richert, J., Li, D.
(2005). Deletion of the SSK1 Response Regulator Gene in Candida albicans Contributes to Enhanced Killing by Human Polymorphonuclear Neutrophils. Infect. Immun.
73: 865-871
[Abstract] [Full Text] -
Li, D., Gurkovska, V., Sheridan, M., Calderone, R., Chauhan, N.
(2004). Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene. Microbiology
150: 3305-3313
[Abstract] [Full Text] -
Brand, A., MacCallum, D. M., Brown, A. J. P., Gow, N. A. R., Odds, F. C.
(2004). Ectopic Expression of URA3 Can Influence the Virulence Phenotypes and Proteome of Candida albicans but Can Be Overcome by Targeted Reintegration of URA3 at the RPS10 Locus. Eukaryot Cell
3: 900-909
[Abstract] [Full Text] -
Kruppa, M., Krom, B. P., Chauhan, N., Bambach, A. V., Cihlar, R. L., Calderone, R. A.
(2004). The Two-Component Signal Transduction Protein Chk1p Regulates Quorum Sensing in Candida albicans. Eukaryot Cell
3: 1062-1065
[Abstract] [Full Text] -
Singh, P., Chauhan, N., Ghosh, A., Dixon, F., Calderone, R.
(2004). SKN7 of Candida albicans: Mutant Construction and Phenotype Analysis. Infect. Immun.
72: 2390-2394
[Abstract] [Full Text] -
Catlett, N. L., Yoder, O. C., Turgeon, B. G.
(2003). Whole-Genome Analysis of Two-Component Signal Transduction Genes in Fungal Pathogens. Eukaryot Cell
2: 1151-1161
[Abstract] [Full Text] -
Jung, W. H., Stateva, L. I.
(2003). The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans. Microbiology
149: 2961-2976
[Abstract] [Full Text] -
Chauhan, N., Inglis, D., Roman, E., Pla, J., Li, D., Calera, J. A., Calderone, R.
(2003). Candida albicans Response Regulator Gene SSK1 Regulates a Subset of Genes Whose Functions Are Associated with Cell Wall Biosynthesis and Adaptation to Oxidative Stress. Eukaryot Cell
2: 1018-1024
[Abstract] [Full Text] -
Moye-Rowley, W. S.
(2003). Regulation of the Transcriptional Response to Oxidative Stress in Fungi: Similarities and Differences. Eukaryot Cell
2: 381-389
[Full Text] -
Furukawa, K., Katsuno, Y., Urao, T., Yabe, T., Yamada-Okabe, T., Yamada-Okabe, H., Yamagata, Y., Abe, K., Nakajima, T.
(2002). Isolation and Functional Analysis of a Gene, tcsB, Encoding a Transmembrane Hybrid-Type Histidine Kinase from Aspergillus nidulans. Appl. Environ. Microbiol.
68: 5304-5310
[Abstract] [Full Text] -
Hohmann, S.
(2002). Osmotic Stress Signaling and Osmoadaptation in Yeasts. Microbiol. Mol. Biol. Rev.
66: 300-372
[Abstract] [Full Text] -
Li, D., Bernhardt, J., Calderone, R.
(2002). Temporal Expression of the Candida albicans Genes CHK1 and CSSK1, Adherence, and Morphogenesis in a Model of Reconstituted Human Esophageal Epithelial Candidiasis. Infect. Immun.
70: 1558-1565
[Abstract] [Full Text] -
Torosantucci, A., Chiani, P., De Bernardis, F., Cassone, A., Calera, J. A., Calderone, R.
(2002). Deletion of the Two-Component Histidine Kinase Gene (CHK1) of Candida albicans Contributes to Enhanced Growth Inhibition and Killing by Human Neutrophils In Vitro. Infect. Immun.
70: 985-987
[Abstract] [Full Text] -
Chandra, J., Kuhn, D. M., Mukherjee, P. K., Hoyer, L. L., McCormick, T., Ghannoum, M. A.
(2001). Biofilm Formation by the Fungal Pathogen Candida albicans: Development, Architecture, and Drug Resistance. J. Bacteriol.
183: 5385-5394
[Abstract] [Full Text] -
Santos, J. L., Shiozaki, K.
(2001). Fungal Histidine Kinases. Sci Signal
2001: re1-re1
[Abstract] [Full Text] -
Brinkman, F. S. L., Macfarlane, E. L. A., Warrener, P., Hancock, R. E. W.
(2001). Evolutionary Relationships among Virulence-Associated Histidine Kinases. Infect. Immun.
69: 5207-5211
[Abstract] [Full Text] -
Jong, A. Y., Stins, M. F., Huang, S.-H., Chen, S. H. M., Kim, K. S.
(2001). Traversal of Candida albicans across Human Blood-Brain Barrier In Vitro. Infect. Immun.
69: 4536-4544
[Abstract] [Full Text] -
Bahn, Y.-S., Sundstrom, P.
(2001). CAP1, an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans. J. Bacteriol.
183: 3211-3223
[Abstract] [Full Text] -
Andaluz, E., Calderone, R., Reyes, G., Larriba, G.
(2001). Phenotypic Analysis and Virulence of Candida albicans LIG4 Mutants. Infect. Immun.
69: 137-147
[Abstract] [Full Text] -
Ernst, J. F.
(2000). Transcription factors in Candida albicans - environmental control of morphogenesis. Microbiology
146: 1763-1774
[Full Text] -
Odds, F. C., Van Nuffel, L., Gow, N. A. R.
(2000). Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host. Microbiology
146: 1881-1889
[Abstract] [Full Text] -
Thomason, P, Kay, R
(2000). Eukaryotic signal transduction via histidine-aspartate phosphorelay. J. Cell Sci.
113: 3141-3150
[Abstract]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»