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.     

Epidemiology of candidaemia in a tertiary care university hospital: 10‐year experience with 381 candidaemia episodes between 2001 and 2010

Defining the epidemiology of and risk factors for candidaemia is necessary to guide empirical treatment. The objectives of this study were to determine the ranking of Candida among positive blood cultures, to define the epidemiology of candidaemia and to investigate patient characteristics and their relationship with C. albicans vs. non‐albicans Candida (NAC) candidaemia. Candidaemia episodes between January 2001 and December 2010 were evaluated retrospectively. Patient characteristics were compared across Candida species. Candida ranked as the fifth most frequently isolated pathogen. Among 381 candidaemia episodes, 58.3% were due to C. albicans, followed by C. parapsilosis (15.2%), C. tropicalis (13.4%) and C. glabrata (6.8%). No statistically significant difference was observed in the distribution of C. albicans vs. NAC (P = 0.432). Patients with NAC had significantly higher rates of haematological disorders (P < 0.001) and neutropenia (P = 0.003), and were older (P = 0.024) than patients with C. albicans, whereas patients with urinary catheters had higher rates of C. albicans (P = 0.007). On species basis, C. tropicalis was more frequently isolated from patients with haematological disorders (P < 0.001) and neutropenia (P = 0.008). Patients with urinary catheters were less likely to have C. parapsilosis (P = 0.043). C. glabrata was most prevalent among patients with solid organ tumours (P = 0.038), but not evident in patients with haematological disorders. Local epidemiological features and risk factors may have important implications for the management of candidaemia.     

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.     

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.     

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.     

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.     

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.     

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.     

Candidosis of the prostate: a rare form of endomycosis

The third case of a culturally and histologically proven candidosis of the prostate in the world literature available to us is reported. Autopsy of a 59-year-old man with metastasizing bronchial carcinoma as predisposing primary disease revealed a local candidosis of the prostate in the left lobe of the prostate, without evidence of a Candida sepsis. Parallel and different aspects in comparison with the other two cases are described.     

Regulation of the Direct Fungicidal Action of Miconazole against Candida albicans ATCC 26790/Die Regulation der direkten fungiziden Wirkung von Miconazol auf Candida albicans ATCC 26790

Summary: The direct lethal action of ł 10⁻⁵ M miconazole against Candida albicans ATCC 11651 depends upon, and is therefore regulated by, growth phase, pH, and whether any miconazole is present during lag phase when susceptibility develops. Certain of these studies were recently extended to C. albicans ATCC 26790 with nearly identical results, suggesting that such regulation is a general phenomenon.
Zusammenfassung: Die direkte letale Wirkung von ≥ 10⁻⁵ M Miconazol gegen Candida albicans ATCC 11651 hängt ab und wird daher reguliert von der Wachstumsphase, dem pH-Wert und davon, ob überhaupt Miconazol während der lag-Phase anwesend ist, in der sich die Suszeptibilität entwickelt Einige dieser Untersuchungen wurden jüngst auf Candida albicans ATCC 26790 erweitert mit fast identischen Resultaten, was zu der Vorstellung führt, daß diese Regulation ein allgemeines Phänomen ist.     

Candida Albicans Strain Differentiation in Cancer Patients Undergoing Therapy: Zur Typisierung von Candida-albicans-Stämmen von Patienten unter Krebs-Therapie

Summary: The study indnded 44 isolates of Candida albicans from cancer patients and 10 isolates from controls. Strain differentiation was carried out by using the resistogram method of Warnock et al. 1979. The method is based on susceptibility tests against sodium selenite, boric acid, cetrimide, sodium periodate and silver nitrate. The results showed no particular association of certain strains with Candida infections in cancer patients.
Zusammenfassung. Die Untersuchungen warden an 44 Candida-albicans-Stämmen Ton Krebs-patieaten und 10 Stämmen von Kontrollen durchgefünrt. Zur Anwendung kam die Resistogram-methode nach Warnock et al. 1979, bei der die Empfindlichkeit der Stämme gegen Natriumseleuit, Borsänre, Cetrimid, Natrium perjodat nnd Silberuitrat untersucht wird. Die Ergebnisse zeigten kein bevorzugtes Auftreten bestimmter Stämme bei Krebspatienten.     

Comparison of 12 liquid media for germ tube production of Candida albicans and C. tropicalis

Infections caused by yeast of the genus Candida are the most common fungal infections, being Candida albicans the most common isolated species among them. The rapid identification of this yeast is mostly based on the production of germ tube in human or animal serum. This study describes the use of 12 different liquid media for germ tube production at 2, 2.5, 3 and 4 h. We examined 193 yeasts, including 157 (81.3%) C. albicans and 36 (18.7%) Candida tropicalis for the production of germ tube. The germ tube production of C. albicans was mostly observed in human serum (98%) followed by rabbit serum (89.8%), brain heart infusion broth (84%) and sheep serum (74.5%) at 2 h. An incubation time exceeding 2 h i.e. 2.5 h or later, C. tropicalis strains were observed to produce germ tubes. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for germ tube production of human serum at 2 h were 98%, 100%, 100% and 92.3% respectively. In all tested sera, an incubation period of more than 2 h improves the sensitivity, but decreases the specificity as well as PPV and NPV of germ tube test (GTT). In conclusion, human serum was observed to be the most appropriate medium to be preferred for GTT, with an incubation period of 2 h.     

Molecular genetics of pathogenic fungi: some recent developments and perspectives

The diagnosis and the treatment of fungal diseases remains problematic in many cases. Difficulties in diagnosis are due (1) to the ubiquitous presence of fungal pathogens that may lead to false positive test results and (2) to difficulties in the evaluation of the aetiological significance of these pathogens. The relatively small number of effective antifungal agents reflects to a large extent on the fact that many aspects of fungal physiology and virulence are not well understood. The methods of molecular genetics provide effective tools for the diagnosis of mycoses and may also contribute to the identification of new targets for antifungals by genetic analyses of fungal virulence. During the last 3 years molecular genetic methods have been developed for the asexual pathogen Candida albicans that may be used for strain identification. This success indicates a general use of molecular genetics for the analysis of fungal pathogenesis.     

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.     

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.     

Production of Phosphatase Enzymes by Different Candida Species: Phosphatase-Aktivitäten bei verschiedenen Candida-Arten

Summary: A total of 99 strains of different Candida species were obtained from 238 specimens, collected from pathological and normal materials. The isolated strains were examined for the production of phosphatase enzyme using phenolphthalein diphosphate as substrate. Candida albicans which was the most frequently recovered yeast was unable to produce the enzyme. On the other hand, Candida tropicalis and Candida krusei were highly active in the enzymatic production. It was noticed that no correlation could exist between the cell growth or decrease in pH with the enzymatic activity. Candida tropicalis and Candida krusei isolated from pathological materials were relatively more productive than isolates recovered from normal samples. This may probably suggest the relation between pathogenicity and enzymatic production in some Candida species.
Zusammenfassung: Insgesamt 99 Stämme von verschiedenen Candida-Arten wurden aus 238 Proben isoliert, die aus pathologischen Veränderungen und von normalen Personen gewonnen worden waren. Die isolierten Stämme wurden auf Phosphatase-Akti-vität untersucht, indem Phenolphthaleindisphosphat als Substrat benutzt wurde. Candida albicans, die am häufigsten isoliert wurde, zeigte keine Enzymaktivität. Andererseits wiesen Candida tropicalis und Candida krusei eine hochaktive Enzymproduktion auf. Eine Korrelation zwischen Enzymaktivität einerseits und Zellvermehrung oder Absinken des pH konnte nicht festgestellt werden. Aus pathologischem Material isolierte Stämme von Candida tropicalis und Candida krusei zeigten höhere Enzymaktivitäten als Stämme, die von Gesunden isoliert worden waren. Dieser Befund könnte möglicherweise auf eine Beziehung zwischen Pathogenität und enzymatischer Aktivität bei einigen Candida-Arten hinweisen.     

Genetic variability of Candida albicans isolates in a university hospital in Hungary

The occurrence and genetic variability of Candida albicans isolates in a Hungarian hospital were examined. Among the 103 Candida isolates, 44 (42.7%) proved to be C. albicans species. Comparing with a previous study carried out in 2002, the percentage of infections caused by C. albicans decreased in Hungary in this period with an increasing incidence of non-albicans species, in accordance with the world-wide trend. The genetic variability of the isolates was examined using mitochondrial DNA (mtDNA), restriction fragment length polymorphism (RFLP), random amplified polymorphic DNA (RAPD) analysis and electrophoretic karyotyping. The examined C. albicans isolates could be clustered into four groups based on their mtDNA profiles. The electrophoretic karyotypes of the isolates were mostly identical to that of the reference strain 1006, with the exception of mtDNA type II isolates. RAPD analy s is could be used to cluster the isolates into different groups, but this clustering was not in complete agreement with their assignment to mtDNA types. Population genetic analyses of the data indicated low amounts of recombination among these C. albicans strains. None of the isolates exhibited decreased susceptibilities to 5-fluorocytosine.     

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.     

Effects of Two Stains on Blastoconidia of Candida albicans: Scanning Electron Microscope Studies. Wirkungen von zwei Farbstoffen auf die Blastosporen von Candida albicans: Untersuchungen mit dem Rasterelektronenmikroskop

Summary:  The authors report observations using scanning electron microscopy (S.E.M.) of cell morphological alterations induced by two stains (crystal violet and malachite green) in cultures of Candida albicans. A marked ultrastructural polymorphism was found. Thus it is suggested that the two stains induced a cellular suffering of the mycete whose functions are then inhibited.
Zusammenfassung:  Die Verfasser berichten über die morphologischen Veränderungen, die von den Farbstoffen Kristallviolett und Malachitgrün bei pathogenen Candida albicans-Stämmen verursacht werden. Auffälliger ultrastruktureller Polymorphismus wurde bei den Sproßzellen festgestellt. Es wird angenommen, daß durch den Farbstoffkontakt die Sproßzellen biologisch inaktiviert werden.     

Serum-independent neutrophil chemotaxins in the yeast phase of Candida, albicans

Cell extracts from 6 strains of Candida albicans grown under different conditions were partially purified and tested for inherent chemotactic activity for human polymorphonuclear granulocytes. Chemotactic activity was demonstrated in the absence of serum using the Boyden chamber technique. No chemokinetic effects of the extracts examined were found using the same method. Cross desensitization experiments of PMN with C. albicans extracts and known leukotaxins (PAF, LTB4, and FMLP) revealed that C. albicans-derived chemotaxins differed from the known chemoattractants. Their possible role in Candida infections is discussed.