scholarly journals Declining Rates of Oropharyngeal Candidiasis and Carriage ofCandida albicansAssociated with Trends Toward Reduced Rates of Carriage of Fluconazole‐ResistantC. albicansin Human Immunodeficiency Virus –Infected Patients

1998 ◽  
Vol 27 (5) ◽  
pp. 1291-1294 ◽  
Author(s):  
Marcelo D. Martins ◽  
Mario Lozano‐Chiu ◽  
John H. Rex
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oropharyngeal Candidiasis ◽  
Immunodeficiency Virus

scholarly journals Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial Candida albicansIsolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis

1998 ◽  
Vol 42 (11) ◽  
pp. 2932-2937 ◽  
Author(s):  
Jose L. Lopez-Ribot ◽  
Robert K. McAtee ◽  
Linda N. Lee ◽  
William R. Kirkpatrick ◽  
Theodore C. White ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
Sequence Data ◽  
Point Mutations ◽  
Oropharyngeal Candidiasis ◽  
Fluconazole Resistance ◽  
Expression Of Genes ◽  
Immunodeficiency Virus ◽  
Major Facilitator ◽  
Abc Transporter Genes

ABSTRACT Resistance to fluconazole is becoming an increasing problem in the management of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Strains obtained from five patients developed decreased fluconazole susceptibility over time. DNA strain typing confirmed the high degree of relatedness among isolates from one patient and the variability among isolates from different patients. Expression of genes involved in development of fluconazole resistance was monitored in each isolate using probes specific for ERG11 (lanosterol 14α-demethylase), MDR1 (a major facilitator), andCDR (ATP-binding cassette or ABC transporter) genes. Increased expression of CDR genes was detected in the series of isolates from two patients. Isolates from one of the two patients also demonstrated increased ERG11 expression, whereas isolates from the other patient did not. Increased levels ofMDR1 mRNA correlated with increased resistance in sequential isolates from another patient. Initial overexpression ofMDR1 with subsequent overexpression of CDRgenes and a final isolate again overexpressing MDR1 were detected in serial isolates from another patient. In another patient, overexpression of these genes was not detected despite an eightfold increase in fluconazole MIC. In this patient, sequence data of theERG11 gene revealed no point mutations associated with decreased susceptibility. Five different patterns of gene expression were observed in isolates recovered from five patients who developed resistance. Therefore, these experiments demonstrate that a variety of mechanisms or combinations of mechanisms are associated with the development of fluconazole drug resistance. Additional studies are needed to estimate the frequency and clinical impact of these mechanisms of resistance.

scholarly journals Low Levels of Antigenic Variability in Fluconazole-Susceptible and -Resistant Candida albicansIsolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis

1999 ◽  
Vol 6 (5) ◽  
pp. 665-670 ◽  
Author(s):  
Jose L. Lopez-Ribot ◽  
Robert K. McAtee ◽  
William R. Kirkpatrick ◽  
Roberto La Valle ◽  
Thomas F. Patterson
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Wall ◽  
Yeast Cells ◽  
National Committee ◽  
Oropharyngeal Candidiasis ◽  
Fluconazole Resistance ◽  
Homogeneous Population ◽  
Antigenic Variability ◽  
Immunodeficiency Virus ◽  
Different Strains

ABSTRACT Three serial isolates of Candida albicans were obtained by direct swab or by oral saline rinses from each of five human immunodeficiency virus-infected patients with recurrent oropharyngeal candidiasis. Genotyping techniques confirmed the presence of a persistent strain in multiple episodes from the same patient, which was different from the strains isolated from other patients. Fluconazole susceptibility was determined by both an agar dilution method and the National Committee for Clinical Laboratory Standards macrobroth procedure. In four of these patients the strains developed fluconazole resistance, and in one patient the strain remained susceptible. The different isolates were propagated as yeast cells on a synthetic medium, and their cell wall proteinaceous components were extracted by treatment with β-mercaptoethanol. Protein and mannoprotein components present in the extracts were analyzed by electrophoresis, immunoblotting, and lectin-blotting techniques. The analysis showed a similar composition, with only minor qualitative and quantitative differences in the polypeptidic and antigenic patterns associated with the cell wall extracts from serial isolates from the same patient, as well as those from different strains isolated from different patients. Use of monospecific antibodies generated against two immunodominant antigens during candidiasis (enolase and the 58-kDa fibrinogen-binding mannoprotein) demonstrated their expression in all isolates tested. Overall, the antigenic makeup of C. albicans strains remained constant during the course of infection and was not affected by development of fluconazole resistance. In contrast to previous reports, the low degree of antigenic variability observed in this study may be due to the fact that the isolates were obtained from a highly homogeneous population of patients and to the uniformity in techniques used for the isolation, storage, and culture of the different strains, as well as extraction methodologies.

scholarly journals Molecular Mechanisms of Fluconazole Resistance in Candida dubliniensis Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis

2002 ◽  
Vol 46 (6) ◽  
pp. 1695-1703 ◽  
Author(s):  
Sofia Perea ◽  
José L. López-Ribot ◽  
Brian L. Wickes ◽  
William R. Kirkpatrick ◽  
Olga P. Dib ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Mechanisms ◽  
Systemic Disease ◽  
Antifungal Susceptibility ◽  
Point Mutations ◽  
Candida Dubliniensis ◽  
Clinical Isolates ◽  
Oropharyngeal Candidiasis ◽  
Mechanisms Of Resistance ◽  
Immunodeficiency Virus

ABSTRACT Candida dubliniensis is a newly identified species of Candida that is phenotypically similar to but genetically distinct from C. albicans. This organism has been recovered with increasing frequency from the oral cavities of human immunodeficiency virus (HIV)-infected and AIDS patients and has been implicated as a causative agent of oral candidiasis and systemic disease. In the present study we characterized the molecular mechanisms of resistance to fluconazole (FLC) in C. dubliniensis clinical isolates from two different HIV-infected patients with oropharyngeal candidiasis. Isolates were identified to the species level by phenotypic and genotypic tests. DNA-typing techniques were used to assess strain identity. Antifungal susceptibility testing was performed by NCCLS techniques. Northern blotting analysis was used to monitor the expression of genes encoding lanosterol demethylase (ERG11) and efflux transporters (CDR and MDR1) in matched sets of C. dubliniensis-susceptible and -resistant isolates by using probes generated from their homologous C. albicans sequences. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. Decreasing susceptibilities to FLC were detected in C. dubliniensis isolates recovered from both patients during the course of treatment. FLC-resistant C. dubliniensis isolates from one patient demonstrated combined upregulation of the MDR1, CDR1, and ERG11 genes. Among the isolates from the second patient, all isolates showing decreased susceptibility to FLC demonstrated upregulation of MDR1, whereas the levels of mRNA for the ERG11 genes remained constant and the expression of CDR genes was negligible. Fourteen point mutations were found in the ERG11 genes of the isolates with decreased susceptibility to FLC. These data demonstrate that the development of azole resistance in C. dublinensis clinical isolates from HIV-infected patients treated with FLC is mediated by multiple molecular mechanisms of resistance, similar to the observations found in the case of C. albicans.

scholarly journals Characterization of the Immune Status of CD8+ T Cells in Oral Lesions of Human Immunodeficiency Virus-Infected Persons with Oropharyngeal Candidiasis

2006 ◽  
Vol 13 (6) ◽  
pp. 678-683 ◽  
Author(s):  
Janet E. Leigh ◽  
Kelly M. McNulty ◽  
Paul L. Fidel
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Adhesion Molecule ◽  
Immune Status ◽  
Central Memory ◽  
Effector Memory ◽  
Oral Lesions ◽  
Oropharyngeal Candidiasis ◽  
Activated State ◽  
Immunodeficiency Virus

ABSTRACT Oropharyngeal candidiasis (OPC) remains the most common oral infection in human immunodeficiency virus (HIV) disease. In a high percentage of HIV+ persons with reduced CD4+ T cells, oral lesions with Candida present at the outer epithelium have an accumulation of CD8+ T cells at the epithelium-lamina propria interface associated with reduced expression of the mucosal cell-trafficking adhesion molecule E-cadherin. The purpose of the present study was to characterize the immune status of these CD8+ T cells. Immunohistochemical staining for phenotypic and activation and costimulation markers was performed on frozen biopsy tissue sections from HIV+ OPC+ persons with accumulated CD8+ T cells. CD8+ T cells consisted primarily of central memory cells by virtue of positive CD45RO (memory) and CD27 (central memory) expression. However, concomitant negative expression of CD62L and CCR7 (effector memory) was suggestive of a transitioning memory phenotype within the tissue. Despite this, the cells are considered to be activated on the basis of positive expression of CD69. The CD8+ T cells are not considered to be NK T cells or anti-HIV CD8+ T cells because of negative or low expression of CD161 and vascular cell adhesion molecule, respectively. These results suggest that the accumulated mucosal migratory-challenged CD8+ T cells are otherwise normal memory T cells in an activated state.

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