Biomedical subjects

Mahmoud A Ghannoum

Publications and source records attributed to Mahmoud A Ghannoum.

At least 19 recordsLinked to original sources

PubMed2006

Cutaneous hypersensitivity to Malassezia sympodialis and dust mite in adult atopic dermatitis with a textile pattern.

Atopic dermatitis (AD) patients with predominantly head and neck involvement react to patch tests of the yeast Malassezia sympodialis (Ms). Protein patch testing methods and interpretation are controversial, but subgroups of AD patients may have unique triggers for disease activity. The aim of the study was to identify clinical characteristics of patients who are patch test-positive to Dermatophagoides farinae/pteronyssinus (Df) and Ms and characterize cutaneous cytokine profiles of the atopy patch tests (APTs). 25 AD patients and 27 control dermatitis patients were patch tested with Ms and Df. Qualitative analysis of Th-1 and Th-2 cytokines by RT-PCR mRNA was obtained from positive APTs. Atopic dermatitis patients with a textile pattern or head and neck involvement demonstrated more positive APTs to Ms than control patients. Early positive APTs (<6 hr) did not exhibit a Th-1 type cytokine profile. The subgroup of adult AD patients with head, neck and upper torso pattern of dermatitis seems most likely to react to Ms (and Df). The immune mechanism of protein patch tests includes a Th-1 cell-mediated component after 6 hr or more.

Adolescent↗

PubMed2006

Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism.

Candida biofilms formed on indwelling medical devices are increasingly associated with severe infections. In this study, we used proteomics and Western and Northern blotting analyses to demonstrate that alcohol dehydrogenase (ADH) is downregulated in Candida biofilms. Disruption of ADH1 significantly (P = 0.0046) enhanced the ability of Candida albicans to form biofilm. Confocal scanning laser microscopy showed that the adh1 mutant formed thicker biofilm than the parent strain (210 microm and 140 microm, respectively). These observations were extended to an engineered human oral mucosa and an in vivo rat model of catheter-associated biofilm. Inhibition of Candida ADH enzyme using disulfiram and 4-methylpyrazole resulted in thicker biofilm (P < 0.05). Moreover, biofilms formed by the adh1 mutant strain produced significantly smaller amounts of ethanol, but larger amounts of acetaldehyde, than biofilms formed by the parent and revertant strains (P < 0.0001), demonstrating that the effect of Adh1p on biofilm formation is mediated by its enzymatic activity. Furthermore, we found that 10% ethanol significantly inhibited biofilm formation in vitro, with complete inhibition of biofilm formation at ethanol concentrations of >/=20%. Similarly, using a clinically relevant rabbit model of catheter-associated biofilm, we found that ethanol treatment inhibited biofilm formation by C. albicans in vivo (P < 0.05) but not by Staphylococcus spp. (P > 0.05), indicating that ethanol specifically inhibits Candida biofilm formation. Taken together, our studies revealed that Adh1p contributes to the ability of C. albicans to form biofilms in vitro and in vivo and that the protein restricts biofilm formation through an ethanol-dependent mechanism. These results are clinically relevant and may suggest novel antibiofilm treatment strategies.

Alcohol Dehydrogenase↗

PubMed2005

A randomized controlled trial assessing the efficacy of fluconazole in the treatment of pediatric tinea capitis.

BACKGROUND: Griseofulvin is considered first-line therapy for tinea capitis, and the Physician's Desk Reference currently recommends 11 mg/kg per day microsize formulation for use in children. Diverse selective pressures have resulted in waning clinical efficacy of griseofulvin, such that higher doses and longer courses of treatment are required. These events have prompted the search for therapeutic alternatives. Fluconazole is one such treatment option, and a variety of studies using this drug have shown promise in the treatment of pediatric tinea capitis. OBJECTIVE: We sought to assess the efficacy, safety, and optimal dose and duration of fluconazole therapy compared with standard-dose griseofulvin (11 mg/kg per day microsize formulation) in the treatment of pediatric tinea capitis. METHODS: This randomized, multicenter, third-party-blind, 3-arm trial was designed as a superiority study to identify a therapeutically superior agent/regimen from the 3 treatment arms: (1) fluconazole 6 mg/kg per day for 3 weeks followed by 3 weeks of placebo, (2) fluconazole 6 mg/kg per day for 6 weeks, and (3) griseofulvin 11 mg/kg per day for 6 weeks. Efficacy variables included mycological, clinical, and combined outcomes. The primary efficacy variable was the combined outcome of the modified intent-to-treat population at week 6. Patient safety was assessed throughout the study. Statistical analysis of the efficacy variables was conducted by means of the Cochran-Mantel-Haenszel test. RESULTS: At the end of treatment, mycological cures were present in 44.5%, 49.6%, and 52.2% of the fluconazole 3-week, fluconazole 6-week, and griseofulvin groups, respectively. Analysis of the primary efficacy variable failed to identify any superior agent, and differences between the combined outcomes of the fluconazole 6-week and griseofulvin groups at week 6 were not significant (P = .32). Regarding mycological, clinical, and combined outcomes, no significant differences between the fluconazole 6-week and griseofulvin groups were detected at any time point in the study. No new safety concerns were raised by this trial, and the incidence of treatment-related adverse events noted in this study is concordant with previous reports. Patients in the fluconazole arms of the study fared similarly. At the end of the trial, the difference in mycological cures between the fluconazole arms was only 7.5%, and increases in the incidence of certain treatment-related adverse events were observed in the fluconazole 6-week group. LIMITATIONS: Adjunctive topical therapies and the impact of infected contacts were not assessed in this trial. CONCLUSION: Systemic therapy with fluconazole 6 mg/kg per day and standard-dose griseofulvin produces comparable but low mycological and clinical cure rates. The limited efficacy of standard-dose griseofulvin and the lack of consensus regarding dose and duration of griseofulvin therapy in tinea capitis emphasize the need for controlled trials to identify optimal treatment parameters. Although the efficacy of fluconazole is no better than that of standard-dose griseofulvin, it may still be useful in select patients with a contraindication or intolerance to high-dose griseofulvin. The outcomes observed in this trial highlight the need to more clearly define the relative importance of adjunctive topical therapies and the evaluation and treatment of infected contacts as factors affecting cure rates.

Antifungal Agents↗

PubMed2005

Candida biofilm: a well-designed protected environment.

Biofilms are colonies of microbial cells encased in a self-produced organic polymeric matrix and represent a common mode of microbial growth. Microbes growing as biofilm are highly resistant to commonly used antimicrobial drugs. Recently, microbial biofilms have gained prominence because of the increase in infections related to indwelling medical devices (IMD). Candida albicans, the pathogenic fungus which is a major cause of morbidity and mortality in blood stream infections, is the most common fungal pathogen isolated from patients with IMD-associated infections. Biofilm formation by Candida species is believed to contribute to invasiveness of these fungal species. We discuss experimental methods used to study fungal biofilms as well as the biology of biofilm formation by clinically relevant Candida species. Recent advances that are discussed in this review include the role of specific, differentially expressed genes and proteins, quorum sensing molecule in C. albicans biofilms, and the correlation between biofilm formation and fungal pathogenesis.

Animals↗

PubMed2005

Cutaneous hypersensitivity to Candida albicans in idiopathic vulvodynia.

We have observed that the majority of our vulvodynia patients give a previous history of vaginal candidiasis that was treated but was followed by symptoms of chronic vulvodynia. 27 vulvodynia patients were patch-tested to a standard series of contact allergens, a customized vulvar series and commensal organisms including ultraviolet-killed Candida albicans. Comparison tests for the commensal organism were made to a group of 13 female atopic dermatitis patients and to 19 female dermatitis patients without a history of childhood flexural dermatitis who were undergoing patch test evaluation in our clinic. Patients reporting vulvodynia were significantly (P < 0.05) more likely to react to C. albicans than the dermatitis comparison group. Interestingly, lower concentrations of C. albicans caused more positive patch tests than higher concentrations. Our findings suggest that previous C. albicans infection may predispose patients to a subsequent hypersensitivity response to C. albicans that is expressed only in areas of high cutaneous peripheral fibre density. Low levels of C. albicans may also be required to elicit this response as high levels of C. albicans may actually result in decreased cutaneous inflammation and decreased intensity of C. albicans patch test responses.

Allergens↗

PubMed2005

Modification of surface properties of biomaterials influences the ability of Candida albicans to form biofilms.

Candida albicans biofilms form on indwelling medical devices (e.g., denture acrylic or intravenous catheters) and are associated with both oral and invasive candidiasis. Here, we determined whether surface modifications of polyetherurethane (Elasthane 80A [E80A]), polycarbonateurethane, and poly(ethyleneterephthalate) (PET) can influence fungal biofilm formation. Polyurethanes were modified by adding 6% polyethylene oxide (6PEO), 6% fluorocarbon, or silicone, while the PET surface was modified to generate hydrophilic, hydrophobic, cationic, or anionic surfaces. Formation of biofilm was quantified by determining metabolic activity and total biomass (dry weight), while its architecture was analyzed by confocal scanning laser microscopy (CSLM). The metabolic activity of biofilm formed by C. albicans on 6PEO-E80A was significantly reduced (by 78%) compared to that of biofilm formed on the nonmodified E80A (optical densities of 0.054 +/- 0.020 and 0.24 +/- 0.10, respectively; P = 0.037). The total biomass of Candida biofilm formed on 6PEO-E80A was 74% lower than that on the nonmodified E80A surface (0.46 +/- 0.15 versus 1.76 +/- 0.32 mg, respectively; P = 0.003). Fungal cells were easily detached from the 6PEO-E80A surface, and we were unable to detect C. albicans biofilm on this surface by CSLM. All other surface modifications allowed formation of C. albicans biofilm, with some differences in thearchitecture. Correlation between contact angle and biofilm formation was observed for polyetherurethane substrates (r = 0.88) but not for PET biomaterials (r = -0.40). This study illustrates that surface modification is a viable approach for identifying surfaces that have antibiofilm characteristics. Investigations into the clinical utility of the identified surfaces are warranted.

Biocompatible Materials↗

PubMed2005

Combination treatment of invasive fungal infections.

The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections.

Animals↗

PubMed2005

Fungal biofilms and antimycotics.

Device-related infections in most nosocomial diseases can be traced to the formation of biofilms (microbial communities encased within a polysaccharide-rich extracellular matrix) by pathogens on surfaces of these devices. Candida species are the most common causative agents of these infections, and biofilms formed by these fungal organisms are associated with drastically enhanced resistance against most antimicrobial agents. This enhanced resistance contributes to the persistence of this fungus despite antifungal therapy. Recent studies showed that Candida biofilms exhibit antifungal resistance against most antifungal agents with the exception of echinocandins and lipid formulations of AMB. This review discusses methods used to evaluate biofilm resistance and provide information on susceptibility pattern of candidal biofilm as well as studies investigating the mechanisms underlying biofilm resistance.

Antifungal Agents↗

PubMed2004

Epidemiologic surveillance of cutaneous fungal infection in the United States from 1999 to 2002.

BACKGROUND: Cutaneous fungal infections are common in the United States, and causative organisms include dermatophytes, yeasts, and nondermatophyte molds. These organisms are in constant competition for their particular environmental niche, often resulting in the emergence of one or more predominant pathogens and displacement of other less competitive species. Changes in the incidence of fungal pathogens can be followed from laboratory culture results of infected cutaneous tissues over time. These data can be used to ascertain past and present trends in incidence, predict increases in antifungal resistance and the adequacy of our current pharmacologic repertoire, and provide insight into future developments. OBJECTIVE: This study identifies epidemiologic trends and the predominant organisms causing superficial fungal infections in the United States. METHODS: A total of 15,381 specimens were collected from clinically suspected tinea corporis, tinea cruris, tinea capitis, tinea faciei, tinea pedis, tinea manuum, and finger and toe onychomycosis from 1999 through 2002. Specimens were submitted to the Center for Medical Mycology in Cleveland, Ohio, for fungal culture and identification, and the incidence of each species was calculated. RESULTS: Dermatophytes remain the most commonly isolated fungal organisms except from clinically suspected finger onychomycosis, in which case Candida species comprise >70% of isolates. Trichophyton rubrum remains the most prevalent fungal pathogen, and increased incidence of this species was observed in finger and toe onychomycosis, tinea corporis and tinea cruris, tinea manuum, and tinea pedis. As the causal agent of tinea capitis, T tonsurans continues to increase in incidence, achieving near exclusionary proportions in the United States. CONCLUSION: Consideration of the current epidemiologic trends in the incidence of cutaneous fungal pathogens is of key importance to investigational efforts, diagnosis, and treatment.

Candida↗

PubMed2004

Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates.

We investigated the biochemical basis for resistance in six sequential clinical isolates of Trichophyton rubrum, from the same patient, which exhibited high-level primary resistance to terbinafine. Cellular ergosterol biosynthesis was measured by incorporation of [14C]acetate, and microsomal squalene epoxidase was assayed by conversion of [3H]squalene to squalene epoxide and lanosterol. Direct comparison was made with a terbinafine-susceptible reference strain of T. rubrum in which squalene epoxidase was previously studied. Resistant isolates displayed normal cellular ergosterol biosynthesis, although slight accumulation of radiolabeled squalene suggested reduced squalene epoxidase activity. Ergosterol biosynthesis in the resistant isolates was only inhibited by terbinafine concentrations above 1 microg/ml (IC50 5 microg/ml). In the reference strain, ergosterol biosynthesis was eliminated by terbinafine at 0.03 microg/ml in accordance with historical data. There was no significant difference in sensitivity between the six resistant isolates. Squalene epoxidase from resistant strains was three orders of magnitude less sensitive than normal enzyme to terbinafine (IC50 of 30 micromol/l and 19 n mol/l respectively). The epoxidase in the resistant strains was also unresponsive to tolnaftate. Resistance to terbinafine in these T. rubrum isolates appears to be due to alterations in the squalene epoxidase gene or a factor essential for its activity.

Antifungal Agents↗

PubMed2004

RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms.

An RT-PCR assay was developed to analyse expression patterns of genes in the Candida albicans ALS (agglutinin-like sequence) family. Inoculation of a reconstituted human buccal epithelium (RHE) model of mucocutaneous candidiasis with strain SC5314 showed destruction of the epithelial layer by C. albicans and also formation of an upper fungal layer that had characteristics similar to a biofilm. RT-PCR analysis of total RNA samples extracted from C. albicans-inoculated buccal RHE showed that ALS1, ALS2, ALS3, ALS4, ALS5 and ALS9 were consistently detected over time as destruction of the RHE progressed. Detection of transcripts from ALS7, and particularly from ALS6, was more sporadic, but not associated with a strictly temporal pattern. The expression pattern of ALS genes in C. albicans cultures used to inoculate the RHE was similar to that observed in the RHE model, suggesting that contact of C. albicans with buccal RHE does little to alter ALS gene expression. RT-PCR analysis of RNA samples extracted from model denture and catheter biofilms showed similar gene expression patterns to the buccal RHE specimens. Results from the RT-PCR analysis of biofilm RNA specimens were consistent between various C. albicans strains during biofilm development and were comparable to gene expression patterns in planktonic cells. The RT-PCR assay described here will be useful for analysis of human clinical specimens and samples from other disease models. The method will provide further insight into the role of ALS genes and their encoded proteins in the diverse interactions between C. albicans and its host.

Agglutinins↗

PubMed2004

Rabbit model of Candida albicans biofilm infection: liposomal amphotericin B antifungal lock therapy.

Catheter-related infections due to Candida albicans biofilms are a leading cause of fungal nosocomial bloodstream infection. In this paper, we describe the development of a model of catheter-associated infection with C. albicans biofilms and show that antifungal lock therapy with liposomal amphotericin B is an effective treatment strategy for these infections. Silicone catheters surgically placed in New Zealand White rabbits were infected with C. albicans, and the rabbits were randomized into three groups: (i) untreated controls, (ii) liposomal amphotericin B lock, and (iii) fluconazole lock. Upon completion of therapy, blood cultures were obtained and the catheters were removed for quantitative culture and scanning electron microscopic analyses. Quantitative cultures revealed that catheters treated with liposomal amphotericin B yielded 0 CFU, which was significant compared to the untreated controls (P < 0.001) and the fluconazole-treated group (P = 0.0079). Although fluconazole treatment tended to have lower CFU compared to untreated controls, there was no difference in mean colony counts between these two groups (1.128 +/- 0.764 and 1.841 +/- 1.141 log(10) CFU/catheter segment, respectively; P = 0.297). Scanning electron microscopy revealed abundant biofilm in the control and fluconazole groups, while the liposomal amphotericin B group was virtually cleared. These findings suggest a possible treatment strategy for the successful salvage of catheters infected with C. albicans biofilms and describe an animal model that may play an important role in the further study of C. albicans biofilm pathogenesis and evaluation of potential antibiofilm agents.

Amphotericin B↗

PubMed2004

Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species.

Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC(2)) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode +/- one dilution range across all 17 laboratories. MIC(2) at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.

Antifungal Agents↗

PubMed2004

Candida parapsilosis characterization in an outbreak setting.

Candida parapsilosis is an important non-albicans species which infects hospitalized patients. No studies have correlated outbreak infections of C. parapsilosis with multiple virulence factors. We used DNA fingerprinting to determine genetic variability among isolates from a C. parapsilosis outbreak and from our clinical database. We compared phenotypic markers of pathogenesis, including adherence, biofilm formation, and protein secretion (secretory aspartic protease [SAP] and phospholipase). Adherence was measured as colony counts on silicone elastomer disks immersed in agar. Biofilms formed on disks were quantified by dry weight. SAP expression was measured by hydrolysis of bovine albumin; a colorimetric assay was used to quantitate phospholipase. DNA fingerprinting indicated that the outbreak isolates were clonal and genetically distinct from our database. Biofilm expression by the outbreak clone was greater than that of sporadic isolates (p < or =0.0005). Adherence and protein secretion did not correlate with strain pathogenicity. These results suggest that biofilm production plays a role in C. parapsilosis outbreaks.

Aspartic Acid Endopeptidases↗

PubMed2004

Candida biofilms: antifungal resistance and emerging therapeutic options.

Intravascular catheter infections are a major cause of morbidity and mortality in hospitalized patients, accounting for the majority of the 200,000 nosocomial bloodstream infections occurring in the US annually. Of the intravenous lines that are culture-positive for Candida, 40% actually represent fungemia, which generally necessitates systemic treatment and line removal to affect cure. Until recently, the reason for the need for device removal was unclear. However, our research group and others have demonstrated a near-total resistance to antifungals by biofilm-associated Candida. Similar to bacterial species, Candida biofilm formation proceeds through early, intermediate and maturation phases. This process is associated with the generation of a polysaccharide extracellular matrix (ECM). Mature C. albicans biofilms have a heterogeneous architecture, in terms of distribution of fungal cells and ECM, and exhibit broad antimicrobial resistance. The mechanisms causing such profound antifungal resistance are beginning to be understood. Recent data indicate that resistance is phase-specific and multifactorial, involving efflux pumps and sterol synthesis (at early and mature biofilm phases, respectively). Neither metabolic quiescence nor the ECM appear to contribute substantially. Susceptibility testing and confocal scanning laser microscopy demonstrated that azoles failed to exert activity against mature Candida biofilms. However, sub-inhibitory concentrations of voriconazole impaired biofilm formation and caused cell morphological aberrations. In contrast, lipid-formulation amphotericins and the echinocandins uniquely exhibited activity against mature biofilms. The mechanisms underlying this ability are unknown. The role of other pharmacological (eg, catheter coatings, antimicrobial peptides and antibiotic locks) and non-pharmacological methods in the prevention and treatment of device-related biofilms is discussed in this review.

Animals↗

PubMed2003

Efficacy of caspofungin combined with amphotericin B against azole-resistant Candida albicans.

The activity of caspofungin (CFG) combined with amphotericin B (AMB) against azole-resistant Candida albicans was evaluated in vitro (chequerboard) and in vivo (murine). CFG+AMB resulted in positive interactive effects in vitro (fractional inhibitory concentration index 0.75). Compared with untreated controls, CFG+AMB prolonged mouse survival (P = 0.006) and compared with AMB alone, CFG+AMB prolonged mouse survival (P = 0.36); however, the latter difference was not significant. CFG+AMB treatment significantly reduced kidney cfu compared with untreated controls and CFG-treated groups (P < or = 0.05 for both comparisons). In addition, this combination reduced brain cfu significantly compared with untreated controls and AMB-treated mice (P = 0.005 and 0.05, respectively).

Amphotericin B↗

PubMed2003

Cutaneous infections dermatophytosis, onychomycosis, and tinea versicolor.

Cutaneous fungal infections cause significant morbidity for healthy and ill patients. The incidence of some dermatomycoses is increasing, despite availability of newer and better topical and systemic treatments. Fungal remnants last months to years under the ideal conditions, allowing continued spread of infection. Mycoses treated in one area may recur because of organism travel from concomitant areas of infection. Failure of patients and physicians to recognize a fungal etiology early may lead to more extensive, severe, or difficult-to-treat infections. Finally, a patient's concurrent illnesses may play a part in susceptibility and ability to manage fungal infections. For these reasons, scientists have studied and developed newer antifungal agents with better efficacy and greater convenience in dosing. These drugs, however, still have side effects and medication interactions that may limit their use in some patients. Better efforts to educate patients and physicians alike may aid in faster recognition and treatment of dermatophytoses. More research is needed to continue to develop drugs suitable for use in a broader range of patients and diagnostic tests that may be quicker or more specific than conventional ones.

Administration, Oral↗

PubMed2003

Differential expression of Candida albicans phospholipase B (PLB1) under various environmental and physiological conditions.

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 degrees C but not at 37 degrees C. However, the protein Plb1p was detected in fungal cells growing at 37 degrees 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 degrees C but not at 37 degrees C. However, growth of C. albicans in YNB/glucose supplemented with serum and phospholipids resulted in expression of PLB1 at 37 degrees 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.

Candida albicans↗