Candida is the fourth most common organism responsible for bloodstream infections in many intensive care units, with Candida albicans being the most predominant species isolated in such cases. It has previously been shown that candidal phospholipase B, encoded by the PLB1 gene, is an important virulence factor for C. albicans pathogenesis. In this study, the effects of environmental factors (carbohydrate source and pH) and physiological conditions (serum, phospholipids and temperature) on the expression of PLB1 by C. albicans cells grown in rich [Sabouraud dextrose broth (SB) or yeast extract/peptone/dextrose] or chemically defined [Lee's, RPMI-1640 or yeast nitrogen base (YNB)] media were investigated. Northern blot analyses revealed that PLB1 mRNA was expressed in C. albicans cells grown in rich media at 30 °C but not at 37 °C. However, the protein Plb1p was detected in fungal cells growing at 37 °C in SB, as determined by Western blot analysis, indicating that although the mRNA for this gene was not detected, the actual gene product was present at this temperature. Expression of PLB1 was detected in cells grown in YNB/glucose at 30 °C but not at 37 °C. However, growth of C. albicans in YNB/glucose supplemented with serum and phospholipids resulted in expression of PLB1 at 37 °C also. Additionally, acidic pH induced higher levels of PLB1 mRNA expression compared to neutral pH, while the morphological form of C. albicans did not have any influence on the expression of this gene. The studies described here show that the expression of PLB1 is regulated by nutritional supplementation, environmental factors and the growth phase of the C. albicans cells, as well as by physiological conditions. The differential expression of PLB1 in response to environmental factors may be correlated to host-specific components available to C. albicans during infection.
BahnY. S.,
SundstromP.
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
Beck-SaguéC. M.,
JarvisW. R.
1993; Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. National Nosocomial Infections Surveillance System. J Infect Dis 167:1247–1251
BrownD. H.Jr,
GiusaniA. D,
ChenX.,
KumamotoC. A.
1999; Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene. Mol Microbiol 34:651–662
CollartM. A.,
OlivieroS.
1993; Preparation of yeast RNA. In Current Protocols in Molecular Biology pp 13.12.1–13.12.5 Edited by
AusubelF. M.,
BretR.,
KingstonR. E.,
MooreD. D.,
SeidmanJ. G.,
SmithJ. A.,
StruhlK.
New York, NY: Wiley;
De BernardisF,
MuhlschlegelF. A,
CassoneA.,
FonziW. A.
1998; The pH of the host niche controls gene expression in and virulence of Candida albicans
. Infect Immun 66:3317–3325
De BernardisF,
AranciaS,
MorelliL,
HubeB,
SanglardD,
SchaferW.,
CassoneA.
1999; Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2 , are virulence factors for Candida vaginitis. J Infect Dis 179:201–208
EdmondM. B,
WallaceS. E,
McClishD. K,
PfallerM. A,
JonesR. N.,
WenzelR. P.
1999; Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 29:239–244
EngenR. L.,
ClarkC. L.
1990; High-performance liquid chromatography determination of erythrocyte membrane phospholipid composition in several animal species. Am J Vet Res 51:577–580
FallonK,
BauschK,
NoonanJ,
HuguenelE.,
TamburiniP.
1997; Role of aspartic proteases in disseminated Candida albicans infection in mice. Infect Immun 65:551–556
HooverC. I,
JantapourM. J,
NewportG,
AgabianN.,
FisherS. J.
1998; Cloning and regulated expression of the Candida albicans phospholipase B ( PLB1 ) gene. FEMS Microbiol Lett 167:163–169
HubeB,
MonodM,
SchofieldD. A,
BrownA. J.,
GowN. A.
1994; Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans
. Mol Microbiol 14:87–99
KaoA. S,
BrandtM. E,
PruittW. R.9 other authors1999; The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin Infect Dis 29:1164–1170
LeeK. L,
BuckleyH. R.,
CampbellC. C.
1975; An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida albicans
. Sabouraudia 13:148–153
LeidichS. D,
IbrahimA. S,
FuY.8 other authors1998; Cloning and disruption of caPLB1 , a phospholipase B gene involved in the pathogenicity of Candida albicans
. J Biol Chem 273:26078–26086
MuhlschlegelF. A.,
FonziW. A.
1997; PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression. Mol Cell Biol 17:5960–5967
MukherjeeP. K.,
GhannoumM. A.
2001; Secretory proteins in fungal virulence. In Fungal Pathogenesis: Principles and Clinical Applications pp 51–79 Edited by
CalderoneR. A.,
CihlarR. L.
New York, NY: Marcel Dekker;
MukherjeeP. K,
SeshanK. R,
LeidichS. D,
ChandraJ,
ColeG. T.,
GhannoumM. A.
2001; Reintroduction of the PLB1 gene into Candida albicans restores virulence in vivo
. Microbiology 147:2585–2597
RamonA. M,
PortaA.,
FonziW. A.
1999; Effect of environmental pH on morphological development of Candida albicans is mediated via the PacC-related transcription factor encoded by PRR2
. J Bacteriol 181:7524–7530
RipeauJ. S,
FiorilloM,
AumontF,
BelhumeurP.,
de RepentignyL.
2002; Evidence for differential expression of Candida albicans virulence genes during oral infection in intact and human immunodeficiency virus type 1-transgenic mice. J Infect Dis 185:1094–1102
StaibP,
WirschingS,
StraussA.,
MorschhauserJ.
2001; Gene regulation and host adaptation mechanisms in Candida albicans
. Int J Med Microbiol 291:183–188
TsuboiR,
MatsudaK,
KoI. J.,
OgawaH.
1989; Correlation between culture medium pH, extracellular proteinase activity, and cell growth of Candida albicans in insoluble stratum corneum-supplemented media. Arch Dermatol Res 281:342–345
WeyS. B,
MoriM,
PfallerM. A,
WoolsonR. F.,
WenzelR. P.
1988; Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med 148:2642–2645
WrightL. C,
ChenS. C,
WilsonC. F,
SimpanyaM. F,
BlackstockR,
CoxG. M,
MurphyJ. W.,
SorrellT. C.
2002; Strain-dependent effects of environmental signals on the production of extracellular phospholipase by Cryptococcus neoformans
. FEMS Microbiol Lett 209:175–181
ZhaoR,
LockhartS. R,
DanielsK.,
SollD. R.
2002; Roles of TUP1 in switching, phase maintenance, and phase-specific gene expression in Candida albicans
. Eukaryotic Cell 1:353–365