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Intracranial fungal aneurysm caused by Candida endocarditis.

We describe a 67-year-old man who died 4 days after suffering a subarachnoid hemorrhage. Autopsy revealed a fresh subarachnoid hemorrhage and a ruptured fungal aneurysm near the trifurcation of the right middle cerebral artery. In comparison with 21 previously reported cases in which the fungal aneurysms were proved to be intracranial, the present case had several characteristic features: the causative fungus of the aneurysm was Candida (only one such case has been reported previously). The aneurysm was caused by direct Candida invasion of the arterial wall from the Candida embolus (previously reported aneurysms have been caused by direct invasion of the arterial wall during fungal meningitis). The source of the Candida was endocarditis (the main sources of fungus in previously reported cases have been sinusitis, dental extraction wounds, and some forms of surgery). We describe the features of this rare autopsy case of a ruptured fungal aneurysm caused by Candida originating from endocarditis and review the literature.

Aged↗

In vitro proteinase production by Candida species.

A total of 290 Candida isolates from patients were investigated for in vitro proteinase production. Overall, sixty percent of these strains were found to be proteinase producers. Of the C. albicans strains, 81.4% of the significant isolates in contrast to 19.7% of nonsignificant isolates were proteinase producers, the difference being statistically significant (P less than 0.001). Amongst the different Candida species, the proteinase production was found not only in Candida albicans, but also in C. tropicalis, C. parapsilosis and C. glabrata. Thus this in vitro method of demonstration of proteinase may be a good adjunct to smear and culture examination in identifying pathogenic Candida species from anatomical sites where they can also be present as commensals.

Candida↗

Pulmonary disease caused by Candida species.

Candida species are often found in sputum specimens. Their role as a possible cause of pulmonary disease is a frequent consideration, particularly in patients receiving immunosuppressive or long-standing antimicrobial therapy. At Memorial Hospital and New York Hospital, 30 patients with histologic evidence of Candida pulmonary infection were identified over a two year period. These infections reached the lungs by hematogenous spread in 10 patients and by aspiration in 16 patients. Most the patients had malignant neoplastic disease. The Candida pulmonary disease appeared to be significant clinical factor in only three cases. Experience from our institutions and from the literature indicates that Candida species rarely cause significant pulmonary disease. When such involvement is extensive, the patient is usually terminally ill from multiple other factors.

Biopsy↗

Phospholipid profiles in the oral yeast Candida.

Individual molecular species of phospholipids can now be readily detected using fast atom-bombardment mass spectrometry (FAB MS). The aim was to obtain detailed information on individual molecular species of Candida phospholipids using FAB MS. Lipids were extracted from Candida isolates and prepared for FAB MS analysis in negative-ion mode. Each isolate yielded several hundred anion peaks. The major anion peaks consistent with the presence of phospholipids included those of mass/charge (m/z) 836, 743, 715, 744 and 834 tentatively identified as phosphatidylethanolamine PE(43:5), phosphatidylglycerol PG(34:3), PG(32:3), PE(36:1) and PE(43:5). Major peaks consistent with the presence of carboxylate anions were of m/z 241, 253, 255, 277, 279, 281, 283, and 307 putatively identified as C15:0, C16:1, C18:3, C18:2, C18:1, C18:0 and C20:2 which also support the putative identifications of phospholipids. Such phospholipid profiles differ from those published for other microorganisms analysed by FAB MS. Quantitative differences were observed between different candidal species. Candida albicans may be readily differentiated from C. glabrata on the basis of its carboxylate anions. Within species, there are quantitative differences in phospholipid profiles. Thus, Candida has a unique combination of phospholipid analogues with potential chemosystematic significance.

Anions↗

Metabolic engineering of Candida yeasts for biotechnological applications.

Candida yeasts represent a versatile yet underexploited platform for industrial biotechnology. These yeasts utilize a remarkably broad range of carbon sources, particularly for hydrophobic carbon sources, coupled with robust growth and diverse biosynthetic capacities, making them promising hosts for sustainable production of chemicals, fuels, and proteins. Despite these advantages, industrial deployment of Candida species has been hindered by concerns regarding opportunistic pathogenicity and the historical lack of efficient genetic manipulation tools, leading to a substantial gap between metabolic potential and practical utilization. Recent advances in functional genomics, genome editing, and systems metabolic engineering are rapidly overcoming these barriers, enabling more precise and efficient strain development. In this review, we systematically summarize recent progress in the metabolic engineering of Candida species as microbial cell factories, with particular emphasis on expanding genetic toolkits, utilizting renewable and non-conventional carbon sources, and biosynthesizing high-value compounds. In addition, we propose a biosafety-oriented classification framework to support their safe industrial deployment. Finally, we discuss current challenges and emerging opportunities, emphasizing that the synergy of synthetic biology and artificial intelligence-driven design holds the key to unlocking the biotechnological potential of Candida yeasts.

Candida↗

Prospective evaluation of Candida species colonization in hospitalized cancer patients: impact on short-term survival in recipients of marrow transplantation and patients with hematological malignancies.

Most hematogenous candidiasis originates from endogenous host flora. The impact of clinically prominent Candida colonization on short-term mortality ( 50 colonies of Candida from non-sterile sites. Fourteen (7.1%) patients were granulocytopenic (ANC <or=100/microl). Nineteen (9.8%) had undergone marrow transplantation, 26 (13.5%) had a hematologic malignancy and 129 (66.5) had non-hematologic cancer. Candida isolates (216) were collected form 210 specimens. Fifty-three (27.5%) patients died; 25 (19.4%) with solid tumors, compared to 16 (61.5%) with hematological malignancy, and 11 (57.9%) BMT recipients (P < 0.001). No deaths were seen in patients with AIDS, and one (7.7%) in a patient with a benign condition (P < 0.001). Twenty-six (29.2%) patients with respiratory tract, 13 (23.2%) with gastrointestinal tract, and three (14.3%) with genitourinary tract colonization died. In patients with multiple-site colonization, mortality was significantly higher (45.5%) (P < 0.05). Mortality was higher in patients with C. glabrata (52.9%) and C. krusei (75%) colonization than with C. albicans (24.1%) (P < 0.025). This study shows that patients with hematologic cancer and recipients of marrow transplant with Candida colonization of multiple body sites, and colonization with C. glabata or C. krusei have poor survival.

AIDS-Related Opportunistic Infections↗

A quantitative study of the survival of two species of Candida on porous and non-porous environmental surfaces and hands.

AIMS: In spite of the importance of many species of Candida as human pathogens, little is known about their ability to survive on animate and inanimate surfaces. Such information is essential in understanding the vehicles and modes of their spread, and in designing proper infection control strategies against them. The aim of this study was to generate comparative quantitative data in this regard. METHODS AND RESULTS: The survival of one clinical isolate each of Candida albicans and C. parapsilosis on two types of hard inanimate surfaces (glass and stainless steel) and two types of fabrics (100% cotton and a blend of 50% cotton and 50% polyester) was evaluated under ambient conditions (air temperature 22 +/- 2 degrees C; relative humidity 45-62%) using quantitative test protocols. The survival of C. albicans was also assessed on human skin, using the fingerpads of adult volunteers as carriers. Each carrier surface received 10 microl of the test suspension containing a soil load to simulate body fluids. When dried on glass and stainless steel carriers, C. albicans and C. parapsilosis remained viable for at least three and 14 days, respectively. Both species could survive for at least 14 days on both types of fabric. On the skin, 20% of the viable C. albicans remained detectable one hour post-inoculation. SIGNIFICANCE AND IMPACT OF THE STUDY: This quantitative and comparative study demonstrated the potential for, and differences in the ability of clinically significant species of Candida to remain viable on porous and non-porous inanimate surfaces as well as on human hands. These results should help in understanding the epidemiology of nosocomial infections due to Candida, and in designing better prevention and control strategies against them.

Adult↗

Phospholipid molecular species distributions of Candida isolates from the UK and Iran.

AIMS: Some species of Candida have been shown to differ with respect to their polar lipid fingerprints when analysed by fast atom bombardment mass spectrometry (FABMS). The aims of this study were to contribute to the existing body of information by (i) examining representatives of species not previously examined and (ii) seeking strains differences associated with country of origin (UK or Iran). METHODS AND RESULTS: FABMS analysis was performed on extracted lipids of 22 strains representing eight species of Candida. The most abundant anion (19 isolates) in spectra was with mass to charge (m/z) 281, corresponding to C18:1 carboxylate. The major phospholipid analogue anions were m/z 515 and 501 (13 strains). These anions were putatively identified as the phosphatidyl molecular species PA(23 : 2) and PA(22 : 2) respectively. Data for strain pairs were compared using the Pearson's coefficient of linear correlation. The values generated were used to cluster strains by nearest-neighbour linkage, using both carboxylate and phospholipid analogue anion data. Isolates of C. parapsilosis were clearly distinct from other isolates. Iranian isolates tended to cluster together when phospholipid anion data were used. However, if carboxylate anion data were used, four Iranian isolates of C. albicans were tightly clustered with three UK isolates, of which two were C. albicans and one was C. dubliniensis. CONCLUSION: It is concluded that both lower, and higher, mass peaks in FABMS spectra can be of potential value in comparing Candida isolates from different countries and from different species. SIGNIFICANCE AND IMPACT OF THE STUDY: When polar lipids of different Candida species are compared, it is important to bear in mind that geographical differences affect results as has been observed with bacteria in similar studies.

Anions↗

Clinical significance of Candida species isolated from cerebrospinal fluid following neurosurgery.

Twenty-one patients for whom adequate clinical data were available were identified in a retrospective review of cases of Candida species isolated from cerebrospinal fluid (CSF) following neurosurgery; 86% had indwelling cerebrospinal devices (shunts). Candida species were isolated from multiple CSF samples from 10 patients; CSF samples from seven of 10 were initially drawn through indwelling devices and those from nine of 10 were obtained by subsequent lumbar punctures. All of these patients were treated with antifungals, although therapy was delayed in 50% of cases until the second positive culture was reported. In 11 cases, Candida was the only isolate recovered from CSF samples drawn through indwelling devices; cultures of subsequent CSF samples obtained by lumbar puncture were negative in 10 of 11 cases. Only two patients for whom a single culture was positive for Candida species were treated with antifungals (both of whom were symptomatic), and none of the untreated patients died of infection. The clinical significance of a single positive CSF sample drawn through an indwelling device is difficult to assess, and a definitive diagnosis may require repeated cultures of CSF samples obtained by lumbar puncture.

Adolescent↗

Candida infections in surgical patients.

Serious Candida infections were seen in 55 surgical patients from January 1977 through December 1980. Most of the patients had compromising underlying conditions and many were elderly. Broad-spectrum antibiotics and total parenteral nutrition (TPN) appeared to predispose patients to Candida infections. Mortality rate from Candida was 38%. A high percentage of patients with positive blood or bile cultures died as a result of Candida infection. Therapy with intravenous amphotericin B was highly effective if given in adequate dosage. No patient receiving more than 200 mg of amphotericin B died, but the mortality rate was 56% in those receiving lower doses.

Adolescent↗

Multiplicity of genes encoding secreted aspartic proteinases in Candida species.

The secreted aspartic proteinases (SAP) of Candida sp. are presumed to be potential virulence factors. In the opportunistic pathogen Candida albicans the proteinase genes identified to date, SAP1, SAP2, SAP3 and SAP4, constitute a multigene family. Before addressing the possible role of each proteinase in virulence, we sought to isolate all the members of this multigene family by screening a genomic library with a SAP1 probe for additional C. albicans SAP genes using low-stringency hybridization conditions. Three putative new members, SAP5, SAP6 and SAP7 were isolated and sequenced. The N-terminal segments of the deduced amino acid sequences of SAP5 and SAP6 contained secretion signal sequences similar to those of other Candida SAPs. Upon comparison and alignment with the other reported SAP amino acid sequences, SAP7 is not only the most divergent protein but also exhibits a much longer putative pro-sequence with a single Lys-Lys putative processing site. Using SAP1 to SAP7 as probes, the overall number of SAP genes in C. albicans was tentatively estimated by low-stringency hybridization to EcoRI-digested genomic DNA. While each isolated SAP gene could be assigned to distinct EcoRI bands, the existence of two additional genes not isolated after screening of the C. albicans gene library was inferred. Furthermore, evidence was obtained for the existence of SAP multigene families in other Candida species such as C. tropicalis, C. parapsilosis and C. guillermondii.

Amino Acid Sequence↗

Testing susceptibility of Candida species to fluconazole and itraconazole using the microdilution assay.

A microdilution system was established for testing the susceptibility of Candida species to fluconazole and itraconazole. The assay used a sodium phosphate-buffered (0.1 mol l-1) Casitone/glucose medium (pH 7.2) supplemented with potassium, iron, magnesium, trace elements and vitamins. Tests were read photometrically after 24 h, and the minimum inhibitory concentration (MIC) was defined as the IC90. In nearly all strains sharp end points were observed. The MICs against Candida species without any known pre-exposure to azoles were found to range from 0.2 to 1.56 micrograms ml-1 for fluconazole and from 2.3 to 12 ng ml-1 for intraconazole. For strains from candidosis patients refractory to treatment with fluconazole the MICs of fluconazole ranged from 6.25 to 100 micrograms ml-1, while those for itraconazole varied between 12 and > 450 ng ml-1. The strains did not respond congruent to both azoles. A similar disparity of the MICs was observed with Candida tropicalis and Candida krusei. The unusually low MICs of itraconazole were attained because (1) the dilution series was prepared from a preformed (concentrated) dilution series in 75% dimethylsulphoxide and not directly by serial dilution in the broth and (2) the incubation was performed in microtitre plates made of quartz glass rather than in the generally used polystyrene microtitre plates.

Antifungal Agents↗

Potential risk factors for infection with Candida spp. in critically ill patients.

The incidence, risk factors and prognostic factors for candidal infection were determined in a prospective study of 280 infected patients. Thirty-one (11%) patients were infected with Candida spp., sub-divided into 18 (58%) with C. albicans, and 13 (42%) with non-albicans spp. (six C. glabrata, three C. parapsilosis, and one each of C. krusei, C. tropicalis, C. guilliermondii and C. lusitaniae). Infection with Candida spp. was always associated with concurrent bacterial infection. By univariate logistic regression analysis, the degree of morbidity and the duration of mechanical ventilation were independent predictive factors for death, but infection with Candida spp., was not. Factors associated with Candida spp. infection were the degree of morbidity, intensive care unit length of stay, alterations of immune response, and the number of medical devices involved. By multivariate logistic regression analysis, the only independent risk factor for candidal infection was intensive care unit length of stay.

Adult↗

Gradual solubilization of Candida cell wall beta-glucan by oxidative degradation in mice.

Candida spp. is a medically important fungi which induces disseminated candidiasis and candidemia in hospitalized immunocompromised patients. The cell wall of Candida is mainly composed of two polysaccharides, mannan and beta-glucan, and at least part of beta-glucan is basically insoluble in H2O or NaOH. We became interested in when and how particulate beta-glucan changes to the soluble form. However, the fate of wall components has not been examined in detail. In this study, modification and solubilization of the cell wall beta-glucan were analyzed in vivo and in vitro. Cells of Candida, intravenously administered to mice (1 mg/mouse), were immediately deposited mainly in liver as determined by 3H-labeled cells. Beta-Glucans were detected in these mice for at least for 6 months by the beta-glucan specific assay. During this period, the insoluble cell wall beta-glucan was gradually solubilized in these organs, probably by oxidative stress of macrophages. Candida cells and particulate beta-glucans were also gradually solubilized in vitro using sodium hypochlorite solution, but part of the cell wall beta-glucan was still insoluble even after treatment with concentrated hypochlorite solution for one day at room temperature. These findings strongly suggested that the fungal cell wall beta-glucans were quite resistant to oxidative metabolism in vivo and in vitro, and thus deposited for quite long period in the host.

Animals↗

Sensitisation of Candida albicans to killing by low-power laser light.

The purpose of this study was to determine whether Candida albicans, and other Candida spp. responsible for HIV-associated candidosis, could be sensitised to killing by low-power laser light. Suspensions of C. albicans were treated with a number of potential photosensitisers, exposed to laser light from a Helium/Neon (HeNe) or Gallium aluminium arsenide (GaAs) laser for 120 s and survivors enumerated. Toluidine blue O (TBO), thionin and crystal violet were able to sensitise the yeast to killing by light from the HeNe laser (energy dose = 876 mJ at a density of 66.36 J/cm2), the kills achieved being 6.8 x 10(6) cfu/ml, 3.1 x 10(6) cfu/ml and 1.3 x 10(6) cfu/ml respectively. TBO was also able to sensitise several other Candida spp. to killing by HeNe laser light. Dihaematoporphyrin ester was not an effective photosensitiser under the conditions employed. Methylene blue, but not aluminium disulphonated phthalocyanine, was able to sensitise C. albicans to killing by light from the GaAs laser (energy dose 1.32 J at a density of 2.04 J/cm2). The viability of the yeast was not affected by exposure to laser light in the absence of the photosensitisers. As killing of dye-sensitised C. albicans, and other Candida spp., could be achieved by exposure to low-power laser light for short periods of time, this approach merits further investigation as a potential therapeutic modality for HIV-associated candidosis.

Aluminum↗

Exfoliative cheilitis (EC) in AIDS: association with Candida infection.

Forty-seven of 165 patients with AIDS (28.5%) showed exfoliative cheilitis (EC), predominantly of the lower lip (n = 37). Histologically, hyphae were revealed in 23 of 47 cases (49%). In 14 of 23 specimens the histological and microbiological findings were in accordance. Smears of the vermilion border revealed Candida albicans in half of the cases (51%); however, combinations with C. krusei, C. tropicalis and C. glabrata were also seen. Twenty of 35 patients given fluconazole either prophylactically or therapeutically showed clinical signs of oral candidiasis. Frequent moistening of the lips may result in infection of the vermilion border with Candida species; consequent desiccation of the lips will lead to scale formation and exfoliation. Smears of the vermilion border of the lower lip of 20 controls with AIDS were positive in four cases. Twenty HIV-negative controls without EC showed negative microbiological results for Candida species. Exfoliative cheilitis may be associated with Candida infection in some cases and may be considered another variant of candidiasis in AIDS patients.

AIDS-Related Opportunistic Infections↗

Isolation and identification of Candida from the oral cavity.

A number of methods of sampling the oral cavity for the presence of candida have been developed. Such techniques play an important role in the diagnosis and management of oral candidosis. In the past, identification of candida isolated from the oral cavity has usually been limited to the genus Candida or to the species C. albicans. However, with the recognition that Candida species differ in the production of putative virulence factors and sensitivity to antifungal agents, greater emphasis has been placed on identification of isolates to species level. As a result a range of commercially available systems for yeast identification can now be used in conjunction with traditional identification procedures.

Antifungal Agents↗