Endocarditis due to Candida albicans in an immunocompromised patient: A case report / Endocarditis por Candida albicans en una paciente inmunocomprometida: presentación de un caso

Case report: Here we present the case of a 53-year-old woman under corticosteroid therapy with a history of rheumatic heart disease, aortic valve replacement, and rheumatoid arthritis, who presented with fungal endocarditis caused by Candida albicans. Even though the patient received 3 years of antifungal prophylaxis with fluconazole, had valve replacement surgery, and received intensive care, the patient finally worsened and died. Conclusions: Comorbidities and corticosteroid therapy predisposed the patient to acquire fungal endocarditis. This case highlights the importance of implementing procedures for the isolation and identification of fungi, and for carrying out antifungal-susceptibility testing, as well as establishing surveillance programs to identify infection-causing species and drug resistance patterns in hospitals. Moreover, designing and upgrading the algorithm for infectious endocarditis is the key to future improvements in diagnosis.(AU)

Antecedentes: La endocarditis fúngica es una enfermedad de baja incidencia cuyo diagnóstico puede ser complicado al confundirse con la endocarditis bacteriana. La endocarditis fúngica se asocia a mayor mortalidad en pacientes inmunocomprometidos. En la práctica clínica, la endocarditis fúngica representa hasta el 10% de las endocarditis infecciosas, con una mortalidad de aproximadamente el 50%. Caso clínico: Mujer de 53 años con endocarditis fúngica por Candida albicans en tratamiento con corticosteroides por antecedentes de fiebre reumática, prótesis de válvula aorta y artritis reumatoide. A pesar de 3 años de profilaxis antifúngica con fluconazol, un nuevo reemplazo valvular y cuidados intensivos, la paciente finalmente empeora y muere. Conclusiones: Las comorbilidades y la toma de corticosteroides predispusieron a la paciente a adquirir una endocarditis fúngica. Esto resalta la importancia de implementar procedimientos de aislamiento, identificación del hongo y pruebas de sensibilidad a los antifúngicos, así como establecer programas de vigilancia para identificar especies causantes de infecciones y patrones de resistencia en hospitales. Además, diseñar y actualizar el algoritmo para un mejor diagnóstico de las endocarditis infecciosas es una cuestión clave.

Attach Me If You Can: Murine Norovirus Binds to Commensal Bacteria and Fungi.

The presence of commensal bacteria enhances both acute and persistent infection of murine noroviruses. For several enteric viral pathogens, mechanisms by which these bacteria enhance infection involve direct interactions between the virus and bacteria. While it has been demonstrated that human noroviruses bind to a variety of commensal bacteria, it is not known if this is also true for murine noroviruses. The goal of this study was to characterize interactions between murine noroviruses and commensal bacteria and determine the impact of bacterial growth conditions, incubation temperature and time, on murine norovirus attachment to microbes that comprise the mammalian microbiome. We show that murine noroviruses bind directly to commensal bacteria and show similar patterns of attachment as human norovirus VLPs examined under the same conditions. Furthermore, while binding levels are not impacted by the growth phase of the bacteria, they do change with time and incubation temperature. We also found that murine norovirus can bind to a commensal fungal species, Candidaalbicans.

Pseudomonas phage inhibition of Candida albicans.

Pseudomonas aeruginosa (Pa) and Candida albicans (Ca) are major bacterial and fungal pathogens in immunocompromised hosts, and notably in the airways of cystic fibrosis patients. The bacteriophages of Pa physically alter biofilms, and were recently shown to inhibit the biofilms of Aspergillus fumigatus. To understand the range of this viral-fungal interaction, we studied Pa phages Pf4 and Pf1, and their interactions with Ca biofilm formation and preformed Ca biofilm. Both forms of Ca biofilm development, as well as planktonic Ca growth, were inhibited by either phage. The inhibition of biofilm was reversed by the addition of iron, suggesting that the mechanism of phage action on Ca involves denial of iron. Birefringence studies on added phage showed an ordered structure of binding to Ca. Electron microscopic observations indicated phage aggregation in the biofilm extracellular matrix. Bacteriophage-fungal interactions may be a general feature with several pathogens in the fungal kingdom.

Ação de chalconas contra a formação de biofilme de Candida albicans / Action of chalcones against biofilm formation of Candida albicans

Candida albicans é uma levedura oportunista que apresenta um conjunto de fatores de virulência que conferem uma maior patogenicidade a estes micro- organismos. Neste trabalho foram estudadas a expressão de determinados fatores de virulência de C. albicans isoladas de cavidade bucal, com ênfase na formação de biofilme, e a atividade antifúngica e o impacto de concentrações subinibitórias de derivados de chalconas na formação de biofilme por estes micro-organismos. Os compostos foram avaliados quanto à toxicidade pelo ensaio de letalidade de Artemia salina e determinação da dose letal a 50% (DL 50 ) ao micro-crustáceo. Nas chalconas sintetizadas, manteve-se o grupameno hidroxil no anel B e foram feitas modificações no anel A que resultaram em diferenças na toxicidade dos compostos variando de 714,3 a 1798,1?g/mL. As leveduras expressaram de forma variável os fatores de virulência com predomínio de alta produção de fosfolipases, aspartil proteinases e com formação do tubo germinativo em até duas horas. A formação de biofilmes foi categorizada em dois grupos distintos nos quais 16 (48%) leveduras foram consideradas como formadoras fracas e 17 (52%) como formadoras fortes. A susceptibilidade as chalconas foi > 1000?g/mL exceto para (E)-1-fenil-3-(4-hidroxifenil) prop-2-em-1-ona que apresentou uma concentração inibitória mínima de 62,5?g/mL para os isolados e de 250?g/mL para a cepa de C. albicans ATCC 10231. Entretanto, concentrações subinibitórias das chalconas apresentaram uma significativa atividade inibitória da formação de biofilme por C. albicans, com graus de inibição variando de 75 a 90%, o que indica a potencial utilização destes compostos na inibição deste importante fator de virulência.(AU)

Candida albicans is an opportunistic yeast that has a number of virulence factors that increase pathogenicity of these micro-organisms. In this study the expression of certain virulence factors were studied of C. albicans isolated from the oral cavity with emphasis on biofilm formation and antifungal activity and the impact of subinibitory concentrations of derivatives of chalconas in biofilm formation by these micro-organisms. The compounds were evaluated for toxicity testing of brine shrimp lethality and determination of 50% lethal dose (LD50) to the micro-crustacean. In synthesized chalconas, remained grouping the hydroxyl in ring B and ring modifications were made on the resulting differences in toxicity of the compounds ranging from 714.3 to 1798.1 ?g/mL. Yeasts shown variable expressed virulence factors with prevalence of high production of phospholipases, aspartyl proteases and formation of germ tube within two hours. The biofilm formation was categorized into two distinct groups in which 16 (48%) yeasts were considered as poor and 17 trainers (52%) as forming strong. Susceptibility was chalcones ? 1000 ?g/mL except for (E)-1-phenyl-3-(4-hydroxyphenyl) prop-2-en-1-one, which showed a minimum inhibitory concentration of 62.5?g/mL for the clinical isolates and 250?g/mL for the strain of C. albicans ATCC 10231. However, subinibitory concentrations of chalcones showed significant inhibitory activity of biofilm formation by C. albicans with degrees of inhibition ranging from 75 to 90%, indicating the potential use of these compounds in the inhibition of this important virulence factor.(AU)

Human pathogenic viruses are retained in and released by Candida albicans biofilm in vitro.

Candida albicans is the most prevalent human fungal pathogen associated with biofilm formation on indwelling medical devices. Under this form, Candida represents an infectious reservoir difficult to eradicate and possibly responsible for systemic, often lethal infections. Currently, no information is available on the occurrence and persistence of pathogenic viruses within C. albicans biofilm. Therefore, the aim of this study was to investigate whether Herpes Simplex Virus type 1 (HSV-1) and Coxsackievirus type B5 (CVB5) can be encompassed in Candida biofilm, retain their infectivity and then be released. Thus, cell-free virus inocula or HSV-1-infected cells were added to 24h-old fungal biofilm in tissue culture plates; 48 h later, the biofilm was detached by washing and energetic scratching and the presence of virus in the rescued material was end-point titrated on VERO cells. Planktonic Candida cultures and samples containing only medium were run in parallel as controls. We found that both HSV-1 and CVB5 free virus particles, as well as HSV-1 infected cells remain embedded in the biofilm retaining their infectivity. As a second step, the influence of biofilm on virus sensitivity to sodium hypochlorite and to specific neutralizing antibodies was investigated. The results showed that virus encompassment in fungal biofilm reduces virus sensitivity to chemical inactivation but does not affect antibody neutralization. Overall, these data provide the first in vitro evidence that viruses can be encompassed within Candida biofilm and then be released. Thus, it may be speculated that Candida biofilm can be a reservoir of viruses too, posing a further health risk.

Ensayo de formación y cuantificación de biopelículas mixtas de Candida albicans y Staphylococcus aureus / Formation and quantification assay of Candida albicans and Staphylococcus aureus mixed biofilm

En el presente estudio se cuantificó la producción de biopelículas individuales y mixtas de Candida albicans y Staphylococcus aureus para determinar si dichas biopelículas mixtas se favorecen sinérgicamente. Los ensayos se realizaron utilizando placas de microtitulación de poliestireno de 96 pocillos de fondo plano, se determinó la actividad metabólica de las células en la biopelícula por medio de la reducción enzimática de una sal de tetrazolio (XTT) a través de los cambios colorimétricos que fueron medidos a 490nm. Para visualizar las biopelículas de cada microorganismo y su cinética de crecimiento se utilizo microscopia láser confocal. La mayor formación de biopelícula se observó en las biopelículas mixtas, seguida de las de Candida albicans y, por último, la menor producción la obtuvo Staphylococcus aureus, lo cual nos sugiere la presencia de una relación sinérgica entre los microorganismos ensayados(AU)

This study quantifies the production of single and mixed biofilms of Candida albicans and Staphylococcus aureus to determine if such mixed biofilms have synergistic effects. Assays were performed using polystyrene microtitre plates of 96 wells, metabolic activity was measured by the enzymatic reduction of a tetrazolium salt (XTT) and colorimetric changes were measured at 490nm. Confocal scanning laser microscopy was used to visualise the biofilms of each microorganism and its growth kinetics. The highest levels of biofilm formation were observed in mixed biofilms, followed by those of Candida albicans only, with the lowest levels of biofilm formation being detected for Staphylococcus aureus; all together these results suggest a synergistic relationship between the tested microorganisms(AU)

Identificação de espécies de Candida na cavidade bucal e susceptibilidade antifúngica em pacientes irradiados em região de cabeça e pescoço e portadores de prótese removível / Identification of candida species in oral cavity and antifungal susceptibility in patients receiving radiation for head and neck cancer and in patients with removable prosthesis

A candidose é a doença de origem fúngica oral mais comum em seres humanos e apresenta uma variedade de características clínicas. Sendo causada principalmente pelo fungo Candida albicans, ela é considerada uma infecção oportunista, afetando principalmente indivíduos que são debilitados por outras doenças. Os avanços da medicina levaram ao prolongamento da sobrevida de pacientes imunocomprometidos, como aqueles pacientes irradiados de cabeça e pescoço que apresentam neoplasias...

Aumento da virulência de Candida albicans após tratamento de quimioterapia / Increased virulence of Candida albicans after antineoplastic chemotherapy

Although yeasts of the genus Candida are part of the normal human oral microbiota, in cancer patients they may be associated with invasive fungal infections. Antineoplastic therapy, with its adverse side effects, increases the likelihood of such infection. One of the important virulence factors is the capacity of yeast cells to adhere to the surface of medical devices inserted into patients. In this study, we tested the in vitro adhesive and film-growing capacity of four Candida albicans samples, isolated before and during chemotherapy from the oral cavity of a patient with adenocarcinoma. Adherence to the orotracheal tube (OTT) and biofilm production were assessed spectrophotometrically and the amount of film growth was estimated by measuring fungal metabolism. Also, the frequency and size of germ tubes were evaluated. The results showed a significant increase in the germ tube size of C. albicans and also an increase in yeast adherence to the OTT after the start of chemotherapy with mitoxantrone.

Embora as leveduras do gênero Candida pertençam a microbiota humana oral normal, em pacientes com câncer a sua presença pode estar associada a infecções fúngicas invasivas. O tratamento quimioterápico, com seus efeitos colaterais, aumenta as chances desta possibilidade. Um dos principais fatores de virulência consiste na capacidade das leveduras de se aderirem a superfície de instrumentos médicos inseridos nos pacientes. O presente estudo avaliou a capacidade in vitro de quatro isolados de Candida albicans, obtidos antes e após o início da quimioterapia de um paciente com adenocarcinoma. Estudos de adesão a tubo endotraqueal; produção de biofilme e quantificação por meio do metabolismo fúngico pelo XTT; frequência e tamanho de tubos germinativos foram realizados. Os resultados demonstraram aumento significante no tamanho do tubo germinativo, assim como o aumento da aderência dessas leveduras ao tubo endotraqueal após o início da quimioterapia com mitoxantrone.

Infecciones micóticas del torrente sanguíneo en hospitales de tercer nivel en Colombia / Fungal bloodstream infections in tertiary care hospitals in Colombia

Antecedentes. Las infecciones micóticas han aumentado en los pacientes críticos y son responsables de una alta morbilidad y mortalidad. Objetivos. Describir la frecuencia de presentación y las especies de hongos responsables de las infecciones del torrente sanguíneo en una red de vigilancia de hospitales de tercer nivel en varias ciudades de Colombia en el periodo entre 2001 y 2007. Métodos. Los datos fueron obtenidos a partir de los laboratorios de microbiología de 27 hospitales de 5 ciudades colombianas. Estos datos fueron incorporados a una base creada en Whonet® versión 5.4 de la OMS. Se analizaron los datos de fungemias de acuerdo a la localización (servicios de cuidado intensivo -UCI- y servicios no-UCI) y se describe la tendencia en el tiempo. Resultados. En 27 hospitales de la red las fungemias correspondieron al 4,1% de los hemocultivos positivos, y las candidemias representaron el 3,7 y el 5,2% de todos los aislamientos en los servicios no-UCI y UCI, respectivamente. Las levaduras fueron los agentes etiológicos responsables en más del 99% de los casos, y Candida albicans fue el microorganismo más identificado tanto en la UCI como fuera de ella, con una menor frecuencia en los últimos años del estudio. En UCI de adultos y en los servicios no-UCI el segundo microorganismo más frecuente fue Candida tropicalis, mientras que en la UCI pediátrica y la neonatal fue Candida parapsilopsis. Cryptococcus neoformans fue el cuarto hongo más frecuentemente identificado. Conclusiones. En Colombia la epidemiología de las infecciones micóticas parece estar cambiando. C. albicans es el principal agente causal de fungemias pero se observa un incremento en el resto de especies del género y una alta frecuencia de C. neoformans(AU)

Background. Fungal infections have increased in critical care patients, causing high morbidity and mortality. Aims. Describe the frequency and responsible fungal species involved in bloodstream fungal infection from 2001 to 2007 in tertiary care level hospitals belonging to a surveillance network in Colombian cities. Methods. Data were collected from a microbiology surveillance network based on 27 hospital laboratories in five Colombian cities. Data were entered into a Whonet® version 5.4 database. Fungemia data were analyzed according to location (Intensive care unit -ICU- vs. non-ICU services). Frequency over time was also described. Results. Fungal infections corresponded to 4.1% of all bloodstream infections. Candidemia represented 3.7% and 5.2% of all isolates in non-ICU and ICU services, respectively. Over 99% of the isolates were yeasts, and Candida albicans was the most frequently isolated organism in and out of the ICU, showing a decreasing trend in the last few years. In the adult ICU and non-ICU services, the second organism most frequently isolated was C. tropicalis, while C. parapsilopsis was the most frequent in the pediatric and neonatal ICU, also showing an overall decreasing trend. Cryptococcus neoformans was the fourth mycotic organism most frequently identified. Conclusions. In Colombia, epidemiology of fungal infections seems to be changing. C. albicans is the principal agent causing bloodstream fungal infection, but an increase of non-albicans species has been observed as well as high frequency of C. neoformans(AU)

Detección de Candida Albicans en lesiones de leucoplasia vellosa bucal de un grupo de pacientes venezolanos VIH+ / Detection of candida albicans in lesions of oral hairy leukoplakia a group of HIV + patients in Venezuela

El objetivo del presente estudio fue determinar la prevalencia de la infección por Candida albicans en lesiones de Leucoplasia Vellosa Bucal (LVB) en un grupo de pacientes VIH+ en una muestra de la población venezolana. Para ello se evaluaron 21 pacientes adultos VIH+, con lesiones clínicas de Leucoplasia Vellosa Bucal, 11 con terapia antiretroviral y 10 sin terapia, y 10 pacientes adultos VIH- con lesiones hiperqueratósicas de la mucosa oral provenientes del Centro para la Atención de Pacientes con Enfermedades Infectocontagiosas de la Facultad de Odontología de la Universidad Central de Venezuela. Los pacientes fueron examinados clinícamente para la detección de lesiones presentes en la mucosa oral, confirmándose el diagnóstico con el estudio histopatológico. La infección por C albicans se determinó mediante biopsias de las lesiones para su estudio histopatológico empleando dos técnicas diferentes, coloración de Pass y método de Grocott, y cultivo microbiológico en medio Agar Sabouraud Resultados: En pacientes VIH+ según los distintos métodos empleados se pudo observar que mediante el cultivo en Agar Sabouraud 6/21 (29%) de los pacientes fueron positivos y 15/21 (71%) fueron negativos. Con respecto a la coloración de Grocott, todos los 21 pacientes fueron positivos, mientras que con la coloración de PAS, 17/21 (81%) de los pacientes fueron positivos y 4/21 (19%) fueron negativos. En el caso de los pacientes VIH- con leucoplasia bucal, 1/10 (10%) resultó positivo mediante el cultivo en Agar Sabouraud y 9/10 (90%) fueron negativos. Mediante la coloración de Grocott todos los pacientes (10) fueron negativos para la presencia del hongo, e iguales resultados fueron obtenidos con la coloración de PAS. Conclusión: Se observó una mayor prevalencia de la infección por C. albicans en pacientes VIH+ lo que demuestra que la presencia del hongo, constituye un factor fuertemente asociado a los pacientes con LVB

The aim of this study was to determine the prevalence of Candida albicans infection in Oral Hairy Leukoplakia (OHL) in Venezuelan HIV+ population. We evaluated 21 HIV+ adults patients with the clinical diagnosis of OHL, 11 under antiretroviral therapy, 10 without and 10 HIV negative adults with hyperkeratotic lesions on the oral mucosa as a control group, from the Center of Infectious diseases, Faculty of Dentistry, Central University of Venezuela. All patients were clinically examined and definitive histopathological diagnosis was made. C albicans was detected by two different histochemical methods: PAS and Groccot and microbiological culture using Agar Sabouraud medium. The results demonstrated that 6/21 (29%) patients were positive by microbiological culture and 15/21 (71%) were negative. All the patients were positive by Grocott special stain while 17/21 (81%) were positive using PAS. In the control group, 1 patient was positive by culture and 9/10 (90%) were negative. Additionally, all the patients were negative by Grocott and PAS. In conclusion, we observed a higher prevalence of C. albicans infection in HIV+ patients, suggesting that the presence of this microorganism may constitute an associated factor in OHL

The role of alternative genetic codes in viral evolution and emergence.

Although the 'universal' genetic code is widespread among life-forms, a number of diverse lineages have evolved unique codon reassignments. The proteomes of these organisms and organelles must, by necessity, use the same codon assignments. Likewise, for an exogenous genetic element, such as an infecting viral genome, to be accurately and completely expressed with the host's translation system, it must employ the same genetic code. This raises a number of intriguing questions regarding the origin and evolution of viruses. In particular, it is extremely unlikely that viruses of hosts utilizing the universal genetic code would emerge, via cross-species transmission, in hosts utilizing alternative codes, and vice versa. Consequently, more parsimonious scenarios for the origins of such viruses include the prolonged co-evolution of viruses with cellular life, or the escape of genetic material from host genomes. Further, we raise the possibility that emerging viruses provide the selection pressure favoring the use of alternative codes in potential hosts, such that the evolution of a variant genetic code acts as a unique and powerful antiviral strategy. As such, in the face of new emerging viruses, hosts with codon reassignments would have a significant selective advantage compared to hosts utilizing the universal code.

Candida albicans de mucosa vaginal: morfotipagem e produção de proteinase / Candida albicans isolated from vaginal secretion: morphotype and proteinase production

Cinquenta e seis isolados de Candida albicans obtidos de mucosa vaginal de mulheres com (n = 30) e sem (n = 26) sintomatologia de candidíase foram identificados pela produção de tubo germinativo em soro bovino fetal e de clamidoconídios em ágar farinha de milho através de assimilação e fermentação de carboidratos. Esses isolados foram submetidos à morfotipagem (características morfológicas da colônia) e testados quanto à produção de proteinase. O morfotipo com código 5.340 (franjas contínuas, de 3 a 5 mm de comprimento, de textura e superfície lisas) foi o mais comumente observado nos dois grupos de mulheres estudadas. Foi vereficada, entretanto, a presença de franjas descontínuas, considerada por representar um fator de virulência, em 8 (26,6 por cento) isolados de C. albicans obtidos de mulheres com sintomas de candidáse vaginal e em apenas 1 (3,8 por cento) dentre os provenientes de mulheres assintomáticas. Esse resultado sugere que as características do morfotipo podem servir como indicador de risco para candidíase. Com relação à atividade enzimática dos isolados, 96,4 por cento das 56 amostras apresentaram produção de proteinase. Os valores de proteinase obtidos neste trabalho não indicaram correlação entre a presença dessa enzima e a capacidade de produzir infecção.

A importância de Candida dublinensis no diagnóstico laboratorial das micoses oportunistas / The importance of candida dublinensis in laboratorial diagnostic of opportunistic mycosis

Candida dublinensis é uma espécie recentemente descrita, filogeneticamente relacionada com C. Albicans e comumente associada a episódios de candidíase oral em pacientes com SIDA. Neste artigo, revisamos aspectos importantes desta espécie como as características clínicas e epidemiológicas da micose, bem como os pricipais aspectos fenotípicos desta levedura. Os problemas de identificação, a suscetibilidade aos antifúngicos e os fatores de virulência são também abordados.