Differences in patient risk factors and source of candidaemia caused by Candida albicans and Candida glabrata

There is an increasing frequency of candidaemia caused by Candida glabrata which has decreased in vitro susceptibility to fluconazole. Differences in risk factors for candidaemia caused by C. glabrata and C. albicans have not been formally evaluated in a diverse patient group. We performed a retrospective study of adult inpatients from January 1, 2003 to April 30, 2008 with C. glabrata and C. albicans candidaemia at a single tertiary care centre in Detroit, Michigan to evaluate for differences in risk factors and presumed source of infection in these groups. Patients’ underlying conditions, risk factors and source of infection (probable or definite) were compared. Among 119 patients, 80 (67.2%) were C. albicans and 39 (32.8%) C. glabrata. Using logistic regression analysis, patients with C. glabrata infection were more likely to have diabetes mellitus (OR 2.43; 95% CI, 1.06–5.54) and abdominal source of infection (OR 4.53, 95% CI, 1.72–11.92). Mortality rates in the two groups were similar. Patients with C. glabrata candidaemia are more likely to be diabetic and have an abdominal source of infection compared with patients with C. albicans.     

Diagnostische Bedeutung des Candida albicans abtotenden Faktors*

Zusammenfassung: In der vorliegenden Arbeit wird die Methodik des Nachweises des Candida albicans abtötenden Faktors und dessen Bewertung beschrieben. Die Untersuchung wurde an Seren von Patienten, die durch eine invasive Kandidose gefährdet sind und von gesunden Menschen durchgeführt. Der candidocide Faktor wurde bei gesunden Menschen, aber auch bei Asthmatikern, die mit Kortikosteroiden behandelt wurden, weiter bei Kranken mit Niereninsuffizienz und bei Leukämikera festgestellt Zur wesentlichen Reduktion dieses Faktors kam es bei Kranken mit Tumoren, Leberzirrhose und besonders bei Diabetikern. Diese Patienten sind deshalb gegen die invasive Form der Kandidose anfällig, denn Candida-Zellen können sich in ihrem Blut ungestört vermehren. Bei den untersuchten Kranken wurden auch komplementfixierende und präzipitierende Anti-körper vorgefunden, die nut dem erhöhten Vorkonunen von Candida im Infektionsmaterial korrelierten. Diese immunologische Reaktion spricht auch für die parasitische Wirkung der Candida-Pilze. Summary: Proof and evaluation of the candidacidal factor ist described in the sera of patients compromised of invasive candidiasis as well as in the sera of healthy persons. The candidacidal factor was found in the sera of healthy persons, of patients treated with corticosteroids, of patients with leukaemia and kidney insufficiency. The factor was substantially reduced in the sera of patients with cancer, cirrhosis and especially with diabetes mellitus. These patients are therefore sensitive to invasive candidiasis as the Candida cells can multiply uninhibited in the serum. Complement fixing antibodies as well as precipitins were found in the investigated patients. The antibodies were in correlation with the high Candida colonisation of these persons. This immunological reaction agrees with the parasitic effect of Candida in these cases.     

Four cases of Candida albicans infections with isolates developing pink colonies on CHROMagar Candida plates

Candida albicans, the most commonly isolated yeast species, is typically identified by its green colony-colour on CHROMagar Candida plates. We here report four cases of Candida albicans infections, in which the initial identification was non-albicans isolates due to a clear pink colour of the colonies on CHROMagar Candida plates. However, classical phenotypic criteria, biochemical assimilation pattern and molecular characterisation identified all four isolates as C. albicans isolates.     

The Chlamydospore of Candida albicans.

Summary:  The chlamydospore of Candida albicans is a disputable growth from the point of view of its development and function. On the basis of light microscopic as well as scanning electron microscopic (SEM) investigations difficulties of distinguishing chlamydospores and their holding structure are discussed by the authors. Attempts are made to draw conclusions from some morphological properties on the ancient, reproductive organ function of the chlamydospores.
Zusammenfassung:  Die Chlamydospore von Candida albicans ist ein Formelement, dessen Entwicklung und Funktion umstritten ist. Auf der Grundlage von licht- und rasterelektronenmikroskopischen Untersuchungen werden die Schwierigkeiten der Unterscheidung der Chlamydosporen und ihrer Trägerapparate von den Autoren diskutiert. Es wird versucht, aus einigen morphologischen und physiologischen Eigenschaften auf die ursprüngliche, reproduktive Organfunktion der Chlamydosporen zu schließen.     

Differentiation of Candida albicans Biotypes by the Method of Odds and Abbott: Differenzierung von Candida albicans-Biotypen mit der Methode von Odds und Abbott

Summary: Biotype differentiation of 69 isolates of Candida albicans from 22 patients was done using the tests of group 1 from the method of Odds and Abbott (1980). In most of the patients only one biotype was found in repeated samplings from different sites. Two coexisting biotypes were found repeatedly in 3 patients with severe predisposing factors. In 2 patients, who received an antimycotic treatment between the samplings, a change of biotype was found.
Zusammenfassung: An 69 Isolaten von Candida (C.) albicans von 22 Patienten wurde eine Differenzierung des Biotyps mit der Gruppe 1 der Methode von Odds und Abbott (1980) durch-geführt. Bei den meisten Patienten wurden in wiederholten Proben von verschiedenen Körper- stellen nur ein Biotyp nachgewiesen. Zwei Biotypen wurden gleichzeitig an 3 Patienten mit schweren prädisponierenden Faktoren wiederholt ermittelt. Bei 2 Patienten, die eine antimyko- tische Behandlung zwischen der Entnahme der Proben erhielten, wurde ein Wechsel des Biotyps nachgewiesen.     

Growth of Candida albicans on the stratum corneum of diabetic and non-diabetic patients

We have used a novel approach to in vitro culture of Candida albicans on cyanoacrylate skin surface strippings. It appears that with this model yeasts and hyphae grew on large surfaces of stratum corneum. The area of extension of the fungal growth was larger on stratum corneum taken from diabetic than from non-diabetic volunteers.     

Adherence ability of Candida africana: a comparative study with Candida albicans and Candida dubliniensis

In this study, we compared the adherence ability to human Hela cells and biofilm formation of three closely related Candida yeast. In our experiments, Candida africana showed poor adhesion ability to human Hela cells and the absence of biofilm formation on polyvinyl chloride strips. Conversely, Candida albicans and Candida dubliniensis formed mature biofilms and stable attachment to Hela cells. To our knowledge, this is the first comparative study reporting data on biofilm formation and adherence to human Hela cells by C. africana.     

Scanning Electron Microscopy of Candida albicans Chlamydospores

Summary:  Candida albicans chlamydospores were studied using scanning electron microscopy method. The various relationships of chlamydospore and pseudohyphae were documented as follow: terminal chlamydospore with or without suspensor cell; lateral chlamydospore with or without suspensor cell; terminal chlamydospore pairs with or without suspensor cell; lateral chlamydospore pairs without suspensor cell.
Zusammenfassung:  Die Chlamydosporen von Candida albicans wurden rasterelektronenmikroskopisch untersucht. Die unterschiedlichen Beziehungen zwischen Chlamydosporen und Pseudohyphen werden wie folgt beschrieben: Terminate Chlamydospore mit oder ohne Suspensorzelle; laterale Chlamydospore mit oder ohne Suspensorzelle; terminale Chlamydosporen-Paare mit oder ohne Suspensorzelle; laterale Chlamydosporen-Paare ohne Suspensorzelle.     

Characterization of the Fibrinogen Binding Factor from Candida albicans and Candida tropicalis in Quantitative Immunoelectrophoresis

Summary:  The fibrinogen binding factor (FBF) was characterized in Candida albicans and Candida tropicalis reference systems by crossed immunoaffinoelectrophoresis (CIAE) with free fibrinogen in the first dimension gel. The FBF of Candida albicans and Candida tropicalis showed the same mobility and reactivity and corresponded to a cross reactive glycoproteic antigen. Thus CIAE provides a useful tool for the identification of biologically active antigens.
Zusammenfassung:  Der Fibrinogen-bindende Faktor (FBF) wurde in Candida albicans- und Candida tropicalis -Referenz-systemen mittels gekreuzter Immunoaffinoelektrophorese (CIAE) mit freien Fibrinogen in der ersten Dimension charakterisiert. Die FBF von Candida albicans und Candida tropicalis zeigten die gleiche Motilität und Reaktivität und entsprachen einem kreuzreagierenden Glykoprotein. Die CIAE erweist sich somit als geeignetes Instrument für die Identifizierung biologisch aktiver Antigene.     

The involvement of physico-chemical interactions in the adhesion of Candida albicans and Candida dubliniensis to epithelial cells

Candida albicans and Candida dubliniensis are two pathogenic yeasts particularly hazardous to immunocompromised patients. Adhesion of yeast cells to epithelium is considered one of the virulence factors and its study is of major importance. The main aim of this study was the comparison of the influence of physico-chemical properties on the adhesion of C. albicans and C. dubliniensis to epithelium. Two strains of each Candida species were used in the adhesion assays to HeLa cells. Adhered cells were enumerated by direct microscopic images observation. Yeast cell surface tension parameters and degree of hydrophobicity were determined by contact angle measurement. Pseudohyphae and hyphae formation was analysed by scanning electron microscopy. Yeast cells presented no statistical differences concerning their physico-chemical surface properties. However, the extent of adhesion to epithelium was different among the four strains. As general conclusion, yeast adhesion to epithelium seems to be strain-dependent and not directly correlated with pseudohyphae formation.     

The protein secretory pathway of Candida albicans

Virulence of the opportunistic pathogen, Candida albicans , relies on an assemblage of attributes. These include the secretion of hydrolytic enzymes, cell surface adhesins, morphological transition between yeast and hyphae, phenotypic switching and biofilm formation. These diverse features are united by their dependence on the protein secretory apparatus for expression. Although the secretory apparatus of C. albicans has been studied limitedly, it appears to conform to the well-conserved eukaryotic system of vesicle-mediated transport between intracellular compartments and the cell surface. Genome comparison with Saccharomyces cerevisiae , however, shows multiple differences whose functional significance is yet unstudied. A unique aspect of the secretory pathway of C. albicans is its structural, and perhaps functional, rearrangement in hyphal vs. yeast cells. This, and evidence of non-conserved secretion mechanism(s), suggest that there is much fundamental knowledge to be derived from the analysis of secretion in C. albican s, which will be relevant to its ability to cause disease.     

Stimulierung der Filamentbildung von Candida albicans durch Kammerwasser

Zusammenfassung:  Kammerwasser von Kaninchen stimuliert das filamentöse Wachstum von Candida albicans in stammabhängiger Weise. Die Zugabe von Kammerwasser zu Blastosporen des Stammes DSM 70010 in Nährbouillon und Inkubation bei 37°C für 18–24 h führt ebenso zur Filamentbildung wie die Inkubation der Blastosporen mit Blutse-rum. Bei Stamm CBS 2730 ergibt nur Serum Filamentwachstum, nicht aber Kammerwasser. Falls im Verlauf einer Candida -Keratitis die Descement'sche Membran durchwachsen wird, könnte die Filamentstimulation durch Kammerwasser klinische Relevanz erlangen.
Summary:  Aqueous humor of rabbit eyes stimulates the filamentous growth of Candida albicans in a strain-dependent manner. Addition of aqueous humor to blastospores of strain DSM 70010 in nutrient broth and incubation at 37°C for 18–24 h yields filaments which are comparable to filaments after incubation of blastospores with blood serum. In strain CBS 2730 serum promotes the formation of filaments but not aqueous humor. If in the course of Candida keratitis the fungus penetrates Descement's membrane, the filamentation in aqueous humor may influence the outcome of the mycosis.     

Habitats for Candida in medical and hygienic respects

The at present acknowledged 163 species of the genus Candida are living in different habitats. Agents of human candidosis have a comparatively restricted natural distribution, and have been discovered primarily in association with men and animals. Candida albicans holds an exceptional position opposite to the nearly 20 non-C. albicans-species with medical importance. Primary habitat is the digestive tract of men and warm-blooded animals. C. albicans is not ubiquitously distributed in the nature. Carriers of Candida may contaminate their immediate environment with yeasts, but that contamination does not usually spread far. C. albicans survives poorly on dry surfaces, a little bit longer in moist materials. Some non-C. albicans-species have their habitat also in the digestive tracts of men and animals, but different to C. albicans they are also ubiquitously distributed in the surroundings (soil, plants, foods, forages) and are much more resistant to environmental influences. The most important source of Candida species in human diseases is endogenous. The via exogen contamination arising mycoses are involved above all by non-C. albicans-species. The different habitats of the Candida species are decisive for the direct and indirect transmission of yeasts to humans and also for the preventive measures against endogenous and exogenous nosocomial Candida mycoses.     

Comparison of the susceptibilities of clinical isolates of Candida albicans and Candida dubliniensis to essential oils

Here, a microdilution technique based on the M27-A2 protocol (NCCLS, 2002) was employed to compare the susceptibilities of Candida albicans and Candida dubliniensis to essential oils extracted from plants used as spices. The chemical compositions of the essential oils were defined based on the analysis of retention indices obtained by gas chromatography–mass spectroscopy. Taken together, the results showed that the activity of the compounds against the two species was similar.     

Veränderungen der Ultrastruktur von Candida albicans unter der Einwirkung von Polyenantibiotika: Ultrastructural Changes in Candida Albicans caused by Polyene Antibiotics

Zusammenfassung: Mittels elektronenmikroskopischer Methode ultradünner Schnitte wurden 24 Stunden alte Kulturen von Candida albicans erforscht, die mit therapeutischen und zehnfach therapeutischen Dosen von Nystatin, Levorin (4000 ED/L und 40000 ED/L) und Amphoglukamin (2000 ED/L und 20000 ED/L) inkubiert waren. Ermittelt wurde eine Vergrößerung der zentralen Vakuole, die Einverleibung von Zytoplasma und Zellorganoiden - Adaptionsetappe. Bei vierundzwanzigstündiger Inkubation mit therapeutischer Konzentration der Präparate, sowie bei Wirkung fungizider Konzentration, sind außer den angeführten Erscheinungen eine Fragmentierung der zytoplasmatischen Membran und Plasmolyse, bei einem Teil der Zellen, Vakuolisation und Nekrose des Zytoplasmas zu beobachten, welch letztere schon nach 3 Stunden sichtbar sind und bei 6 und 24 Stunden Inkubationszeit zunehmen (Destruktionsetappe). Der Einschluß von Fragmenten von Zytoplasma, Lomasomen und anderer Zellorganoiden in die zentrale Vakuole, die Verdichtung und Vakuolisierung des Zytoplasmas führt zur Verstärkung der autolytischen Prozesse und zur Zerstörung der Pilzzelle. Der Grad der destruktiven Veränderungen steht in Abhängigkeit zur Konzentration des Präparats und zur Inkubationsdauer und ist etwas höher bei der Wirkung von Amphoglukamin. Summary: 24 hours old cultures of Candida albicans were exposed to therapeutical and tenfold therapeutical concentrations of nystatin and levorin (4000 IU/L and 40 000 IU/L) and of amphoglucamin (2000 and 20 000 IU/L) and afterwards were studied in ultra thin sections with the transmission electron microscope. Early changes were an enlargement of the central vacuole with incorporation of cytoplasma and cell organells: this is the adaptation phase. After 24 hours of incubation with therapeutical concentrations or under the influence of fungicidal concentrations fragmentation of the cytoplasmic membrane and plasmolysis can be seen in addition to the early changes. In some of the cells, vacuolisation and necrosis of the cytoplasma can be observed. The latter changes appear already after 3 hours' incubation and increase after 6 or 24 hours of incubation. This is the destruction phase. The incorporation of cytoplasmic fragments, of lomasomes and of other cell organells into the central vacuole as well as condensation and vacuolisation of the cytoplasm accelerate the autolytic processes and the destruction of the fungal cell. The degree of cell destruction is correlated to the concentration of the antibiotic and to the incubation time, and it is slightly more intense when amphoglucamin is applied.     

Evaluation of Mueller-Hinton-agar as a simple medium for the germ tube production of Candida albicans and Candida dubliniensis

Candida albicans is the most frequently isolated yeast species from clinical specimens. A classical rapid presumptive differentiation from non- albicans species is based on its ability to produce germ tubes after incubation in human serum. The only non- albicans Candida species producing germ tubes is Candida dubliniensis. In this study, we evaluated Mueller-Hinton-agar (MH-agar) as a medium for germ tube formation of C. albicans and C. dubliniensis . A total of 859 yeast isolates from stool samples, including 632 strains of C. albicans , 10 C. dubliniensis and 217 other yeast strains from 20 different species, were grown on Sabouraud glucose (2%) agar at 37 °C for 24–72 h. Species were identified by standard methods. For the germ tube test (GTT), an inoculum from a single colony was streaked onto a MH-agar plate and covered by a sterile coverslip. After incubation at 37 °C for 2 h, the MH plates were examined using a light microscope at ×200. The GTT was positive in 578 of 632 C. albicans strains (sensitivity 91.5%), in six of 10 C. dubliniensis strains (sensitivity 60.0%), and in none of the other yeast strains. MH-agar is a suitable medium for the GTT and the presumptive identification of C. albicans . It is safer to use than human serum and is widely available in microbiology laboratories.     

Zur Korrelation von Biotyp und Antimykotika-sensibilität bei Candida albicans. On the Correlation of Biotype and Antimicrobial Susceptibility in Candida albicans

Zusammenfassung: 54 rezente Candida albicans-isolate von Haut und angrenzenden Schleimhäuten wurden zunächst auf Grand der von Odds und Abbott 1983 (23) angegebenen Eigenschaften biotypisiert. Anschließend wurde ihre Antimykotikaempfindlichkeit nüt Hilfe von Agardilutions- und Mikrodilutionstest untersucht. Insgesamt fanden sich 42 verschiedene Biotypen, die im häufigsten Falle viermal vertreten waren. Die minimalen Hemmkonzentrationen (MHK) von 5-Fluorcytosin (5FC) schwankten zwischen 0,016 und mehr als 128 mg/l. Die IC₃₀-Werte nach Johnson et al. 1984 (17) reichten von 0,25 bis mehr als 64 mg/l. Bei Ketoconazol lagen die MHK-Werte zwischen 32 und 128 mg/l. Wie angesichts dieser geringen Bandbreite nicht anders zu erwarten, fand sich bei diesem Antimykotikum keine klare Korrelation zwischen Biotyp und minimalen Hemmkonzentrationen. Bei 5FC ließ sich demgegenüber eine derartige Korrelation innerhalb der Biotypengruppen 1 und 3 nachweisen: Innerhalb der Gruppe 1 erwiesen sich die mit den Kodenummern 4 und 5 als besonders resistent. Innerhalb der Gruppe 3 bestand ein entsprechender Zusammenhang mit der Kodenummer 7. Summary: 54 recent clinical mucocutaneous isolates of Candida albicans were differentiated using several different characteristics as described 1983 by Odds and Abbott (23). In addition antimicrobial susceptibility testing was performed using both the agardilution and microdilution method. 42 different biotypes were found, the most frequent one turning up four times. The minimum inhibitory concentrations (MIC) of 5-fluorocytosine (5FC) ranged from 0.016 to more than 128 mg/l. The IC₃₀ values according to Johnson et al. 1984 (17) lay between 0.25 and more than 64 mg/l. With ketoconazole the MICs ranged from 32 to 128 mg/l. As could be exspected from this small range no clear correlation could be demonstrated between biotype and MIC with this antimycotic. With 5FC, however, there was a correlation within the biotype groups 1 and 3: within group 1 the strains carrying the code numbers 4 and 5 were especially resistent to 5FC. Within group 3 this especially was the case with code number 7.     

Candida albicans and the principle of opportunism. An essay

Zusammenfassung.   Die Begriffe Opportunismus und Opportunist werden seit langem in vielerlei Hinsicht in Politik, Sozialwissenschaften, Wirtschaftswissenschaften und Naturwissenschaften benutzt. Trotzdem sind diese Begriffe nur unzureichend definiert. Es werden die verschiedenen Bedeutungen dieser Begriffe in den unterschiedlichen Zusammenhängen mit besonderem Augenmerk auf dem mikrobiologischen Bereich diskutiert, und hier im Speziellen in Zusammenhang mit Candida albicans , die neben Pseudomonas aeruginosa am häufigsten als Opportunist bezeichnet oder des Opportunismus verdächtigt wird.     

Virulence of Candida albicans mutants

Mutant strains of the fungal pathogen Candida albicans blocked in pyrimidine transport and salvage metabolism were tested for virulence in various animal models. The growth rate, germination and proteolytic enzyme production did not correlate with the virulence of the strains. However, a defect in the uridine transport system significantly decreased virulence in murine candidosis, although it had no effect in vaginal candidosis or in a Candida cyst model. It remains unclear whether this is due to the differing host defence mechanisms involved in systemic and superficial mycoses, or to the different requirements of the fungal systems for adherence and tissue invasion in the two types of infection.