scholarly journals Inducible Azole Resistance Associated with a Heterogeneous Phenotype in Candida albicans

2001 ◽  
Vol 45 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Kieren A. Marr ◽  
Christopher N. Lyons ◽  
Kien Ha ◽  
Tige R. Rustad ◽  
Theodore C. White
Keyword(s):  
Candida Albicans ◽  
Efflux Pump ◽  
Population Analysis ◽  
Rapid Development ◽  
Oral Candidiasis ◽  
Heterogeneous Population ◽  
Azole Resistance ◽  
Serial Transfer ◽  
Development Of Resistance ◽  
Immunosuppressed Patients

ABSTRACT The development of azole resistance in Candida albicansis most problematic in patients with AIDS who receive long courses of drug for therapy or prevention of oral candidiasis. Recently, the rapid development of resistance was noted in other immunosuppressed patients who developed disseminated candidiasis despite fluconazole prophylaxis. One of these series of C. albicans isolates became resistant, with an associated increase in mRNA specific for aCDR ATP-binding cassette transporter efflux pump (K. A. Marr, C. N. Lyons, T. R. Rustad, R. A. Bowden, and T. C. White, Antimicrob. Agents Chemother. 42:2584–2589, 1998). Here we study this series of C. albicans isolates further and examine the mechanism of azole resistance in a second series ofC. albicans isolates that caused disseminated infection in a recipient of bone marrow transplantation. The susceptible isolates in both series become resistant to fluconazole after serial growth in the presence of drug, while the resistant isolates in both series become susceptible after serial transfer in the absence of drug. Population analysis of the inducible, transiently resistant isolates reveals a heterogeneous population of fluconazole-susceptible and -resistant cells. We conclude that the rapid development of azole resistance occurs by a mechanism that involves selection of a resistant clone from a heterogeneous population of cells.

scholarly journals Fluconazole versus Candida albicans: A Complex Relationship

1998 ◽  
Vol 42 (11) ◽  
pp. 2938-2942 ◽  
Author(s):  
John R. Graybill ◽  
Eleanor Montalbo ◽  
William R. Kirkpatrick ◽  
Michael F. Luther ◽  
Sanjay G. Revankar ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Efflux Pump ◽  
Progressive Increase ◽  
Oropharyngeal Candidiasis ◽  
Fluconazole Resistance ◽  
Development Of Resistance ◽  
Resistant Strains ◽  
Drug Efflux Pump ◽  
Renal Infection ◽  
Higher Doses

ABSTRACT A murine model of systemic candidiasis was used to assess the virulence of serial Candida albicans strains for which fluconazole MICs were increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 μg/ml; range, 0.25 to 4 μg/ml) to resistant (MIC ≥ 16 μg/ml; range, 16 to ≥128 μg/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of CDR, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy. Resistant isolates from both of these patients exhibited overexpression of MDR. This study demonstrates that decreased virulence of serial C. albicans isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection.

scholarly journals Physical-chemical and microbiological stability of biotherapy Candida albicans RC in different potencies

2021 ◽  
Vol 10 (36) ◽  
pp. 155-157
Author(s):  
Fortune Honsani ◽  
Cristiane Larosa ◽  
Flavia Gonçalves ◽  
Danielle Avellar ◽  
Helena Toma ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Candida Albicans ◽  
Oral Candidiasis ◽  
Colony Growth ◽  
Storage Conditions ◽  
Physical Chemical ◽  
Significant Difference ◽  
Immunosuppressed Patients ◽  
Microbiological Stability ◽  
Microbiological Analyses

Introduction: Oral Candidiasis is an opportunist fungal infection, with high incidence in HIV and immunosuppressed patients and Candida albicans is the most common causing agent. In some cases, it can evolve to resistant injuries to antifungal conventional therapy. According to Brazilian Homeopathic Pharmacopeia (BHP) [1], biotherapic medicines are prepared from chemically undefined biological products. Biotherapics created by Brazilian doctor Roberto Costa (RC) have a different homeopathic compounding technique, as its dynamization starts from the ethiologic agent of the illness in its alive form, which present higher capability to stimulate the host immunological system [2,3]. Aim: The goal of this study was evaluate the physical-chemical and microbiological stability of Candida albicans RC potencies under different conditions of storage. Methodology: To prepare the biotherapics, one part of Candida albicans yeast suspension (109 cell/ml) was diluted in 9 parts of sterile distillated water. After preparing this 1:10 dilution, the sample was undergone 100 succussions, resulting in the first decimal dilution (1x). Then, one part of this solution was diluted in 9 parts of sterile distillated water and submitted to 100 succussions, generating the 2x. This process was successively repeated following BHP, until 30x. Water 30x was prepared by the same technique, as control. All the solutions were prepared in aseptic and sterile conditions. Biotherapics 6x, 12x, 18x, 24x, 30x and water 30x were storage under refrigeration (2 to 8°C) and at room temperate (25°C) during 8 weeks. Every 15 days, the following parameters were analyzed: pH, electrical conductivity, UV absorbance (260 and 280 nm). Microbiological analyses were performed after 3 weeks by colony forming unit (CFU) method [4]. Results: The preliminary analyses performed at times zero, 15, 30 and 45 days suggest that electrical conductivity of these solutions tend to increase proportionally to storage time without significant differences due to temperature storage conditions. There was no statistically significant difference detected in pH values. Measures of absorbance of different biotherapic potencies under both conditions of storage are in course. Microbiological analyses showed no colony growth, but in the 1x sample analyzed at time zero, indicating the viability of the fungus. Conclusion: Further experiments are being carried out in order to confirm the preliminary data obtained.

Efek Proteksi Ekstrak Etanol Stichopus hermanii Terhadap Jumlah Limfosit pada Tikus yang Terpapar Asap Rokok dan Diinduksi Candida albicans

DENTA ◽  
2015 ◽  
Vol 9 (2) ◽  
pp. 146
Author(s):  
Auliasari Yunanda ◽  
Syamsulina Revianti ◽  
Isidora Karsini
Keyword(s):  
Candida Albicans ◽  
Oral Candidiasis ◽  
Control Group ◽  
Post Test

<p><strong><em>Latar Belakang: </em></strong>Merokok berhubungan dengan jamur rongga mulut yang dapat mengakibatkan <em>oral candidiasis</em>. <em>Stichopus hermanii</em><em> </em>mengandung efek antioksidan, antifungi dan immunostimulator. <strong><em>Tujuan: </em></strong>Mengevaluasi efek proteksi ekstrak <em>Stichopus hermanii </em>terhadap jumlah limfosit pada tikus Wistar yang terpapar asap rokok dan diinduksi <em>C.albicans.<strong> Bahan dan Metode: </strong></em>Rancangan penelitian ini adalah <em>post test-only control group</em> <em>design</em><strong><em>. </em></strong>42 ekor tikus Wistar jantan, dibagi menjadi 7 kelompok, Kelompok1 (saline 0,1mL, udara segar, CMC-Na 0,2%), Kelompok2 (saline 0,1mL, asap rokok, CMC-Na 0,2%), Kelompok3 (<em>C.albicans </em>0,1mL, udara segar, CMC-Na 0,2%), Kelompok4 (<em>C.albicans </em>0,1mL, asap rokok, CMC-Na 0,2%), Kelompok5 (saline 0,1mL, asap rokok, ekstrak <em>Stichopus hermanii</em> 0,02mg/kgBB), Kelompok6 (<em>C.albicans</em> 0,1mL, udara segar, ekstrak <em>Stichopus hermanii </em>0,02mg/kgBB), Kelompok7 (<em>C.albicans </em>0,1 mL, asap rokok, ekstrak <em>Stichopus hermanii </em>0,02mg/kgBB). Tikus Wistar diinduksi <em>C.albicans</em> 1 minggu, terpapar asap rokok 8 minggu, dan diberi ekstrak <em>Stichopus hermanii</em> 8 minggu. Selanjutnya, tikus Wistar dikorbankan setelah 2 bulan perlakuan. Jumlah limfosit dihitung melalui metode hapusan darah dengan <em>different counting</em> dibawah mikroskop cahaya dengan pembesaran 1000x. Data yang diperoleh dianalisis menggunakan uji <em>Kruskal-Wallis</em> dan <em>Mann-Whitney</em>.<strong><em> Hasil:</em></strong> Kelompok yang terpapar asap rokok dan diinduksi C.albicans memiliki dapat menurunkan jumlah limfosit, kelompok suplementasi menggunakan ekstrak ethanol <em>Stichopus hermanii</em> dapat meningkatkan jumlah limfosit<em>. </em><strong><em>S</em></strong><strong><em>impulan:</em></strong><strong> </strong>Suplementasi ekstrak <em>Stichopus hermanii</em> memiliki efek protektif untuk memicu proliferasi limfosit pada tikus Wistar setelah paparan asap rokok dan induksi <em>C.albicans</em>.</p>

scholarly journals Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

2015 ◽  
Vol 83 (7) ◽  
pp. 2614-2626 ◽  
Author(s):  
Rohitashw Kumar ◽  
Darpan Saraswat ◽  
Swetha Tati ◽  
Mira Edgerton
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Oral Candidiasis ◽  
Oral Microbiome ◽  
Proteinase Activity ◽  
Adhesion Properties ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Cell Cell

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually withC. albicanscells overexpressing Sap6 (SAP6OE and a Δsap8strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6strain was attenuated. These hypervirulent strains had highly aggregative colony structurein vitroand higher secreted proteinase activity; however, the levels of proteinase activity ofC. albicansSaps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6OE and Δsap8cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increasedC. albicansadhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

scholarly journals Oral Candidiasis and COVID-19 in Users of Removable Dentures: Is Special Oral Care Needed?

Gerontology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Laura Silva Jerônimo ◽  
Rafael Paschoal Esteves Lima ◽  
Thaís Yumi Umeda Suzuki ◽  
José Augusto César Discacciati ◽  
Cláudia Lopes Brilhante Bhering
Keyword(s):  
Mechanical Ventilation ◽  
Candida Albicans ◽  
Oral Health ◽  
Early Diagnosis ◽  
Elderly Patients ◽  
Oral Candidiasis ◽  
Oral Care ◽  
Antifungal Treatment ◽  
Immunocompromised Patients ◽  
Appropriate Care

Elderly patients with systemic disorders and immunocompromised patients seem to have a higher risk of developing morbidity from COVID-19. <i>Candida albicans</i> (<i>C. albicans</i>) is a potentially dangerous pathogen for these patients, especially for denture wearers with prosthetic stomatitis who require mechanical ventilation. <i>C. albicans</i> infection, the main candidiasis infection associated with denture wear, can complicate COVID-19 and increase the associated morbidity and mortality. Therefore, early diagnosis of <i>C. albicans</i> infection in COVID-19 patients is important to establish more effective antifungal treatment methods and prophylaxis strategies. Hospitalized COVID-19 patients should undergo an oral examination to assess their oral health, and those with poor oral health should receive the appropriate care and monitoring.

scholarly journals Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 998
Author(s):  
Virgínia Barreto Lordello ◽  
Andréia Bagliotti Meneguin ◽  
Sarah Raquel de Annunzio ◽  
Maria Pía Taranto ◽  
Marlus Chorilli ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Enterococcus Faecium ◽  
Potato Starch ◽  
Oral Candidiasis ◽  
Candida Spp ◽  
Sem Images ◽  
Control Film ◽  
In Vitro Antifungal Activity

Background: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. Methods and Results: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g−1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. Conclusion: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

Azole resistance inCandida albicansfrom animals: Highlights on efflux pump activity and gene overexpression

Mycoses ◽  
2017 ◽  
Vol 60 (7) ◽  
pp. 462-468 ◽  
Author(s):  
Marcos Fábio Gadelha Rocha ◽  
Silviane Praciano Bandeira ◽  
Lucas Pereira de Alencar ◽  
Luciana Magalhães Melo ◽  
Jamille Alencar Sales ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Gene Overexpression ◽  
Azole Resistance ◽  
Pump Activity

scholarly journals Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yun C. Chang ◽  
Ami Khanal Lamichhane ◽  
Hongyi Cai ◽  
Peter J. Walter ◽  
John E. Bennett ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
High Frequency ◽  
Antifungal Agent ◽  
Inhibitory Concentration ◽  
Glucuronic Acid ◽  
Rapid Development ◽  
Acid Synthesis ◽  
Transcriptional Factor ◽  
Development Of Resistance ◽  
Acid Accumulation

AbstractThe antifungal agent 5-fluorocytosine (5-FC) is used for the treatment of several mycoses, but is unsuitable for monotherapy due to the rapid development of resistance. Here, we show that cryptococci develop resistance to 5-FC at a high frequency when exposed to concentrations several fold above the minimal inhibitory concentration. The genomes of resistant clones contain alterations in genes relevant as well as irrelevant for 5-FC resistance, suggesting that 5-FC may be mutagenic at moderate concentrations. Mutations in FCY2 (encoding a known permease for 5-FC uptake), FCY1, FUR1, UXS1 (encoding an enzyme that converts UDP-glucuronic acid to UDP-xylose) and URA6 contribute to 5-FC resistance. The uxs1 mutants accumulate UDP-glucuronic acid, which appears to down-regulate expression of permease FCY2 and reduce cellular uptake of the drug. Additional mutations in genes known to be required for UDP-glucuronic acid synthesis (UGD1) or a transcriptional factor NRG1 suppress UDP-glucuronic acid accumulation and 5-FC resistance in the uxs1 mutants.

scholarly journals Staphylococcus aureus Mutants Isolated via Exposure to Nonfluorinated Quinolones: Detection of Known and Unique Mutations

2001 ◽  
Vol 45 (12) ◽  
pp. 3422-3426 ◽  
Author(s):  
Siddhartha Roychoudhury ◽  
Tracy L. Twinem ◽  
Kelly M. Makin ◽  
Mark A. Nienaber ◽  
Chuiying Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Sequence Analysis ◽  
Efflux Pump ◽  
Serial Passage ◽  
Efflux Pump Inhibitor ◽  
In Vitro Development ◽  
Development Of Resistance ◽  
High Level ◽  
Vitro Development

ABSTRACT The in vitro development of resistance to the new nonfluorinated quinolones (NFQs; PGE 9262932, PGE 4175997, and PGE 9509924) was investigated in Staphylococcus aureus. At concentrations two times the MIC, step 1 mutants were isolated more frequently with ciprofloxacin and trovafloxacin (9.1 × 10−8 and 5.7 × 10−9, respectively) than with the NFQs, gatifloxacin, or clinafloxacin (<5.7 × 10−10). Step 2 and step 3 mutants were selected via exposure of a step 1 mutant (selected with trovafloxacin) to four times the MICs of trovafloxacin and PGE 9262932. The step 1 mutant contained the known Ser80-Phe mutation in GrlA, and the step 2 and step 3 mutants contained the known Ser80-Phe and Ser84-Leu mutations in GrlA and GyrA, respectively. Compared to ciprofloxacin, the NFQs were 8-fold more potent against the parent and 16- to 128-fold more potent against the step 3 mutants. Mutants with high-level NFQ resistance (MIC, 32 μg/ml) were isolated by the spiral plater-based serial passage technique. DNA sequence analysis of three such mutants revealed the following mutations: (i) Ser84-Leu in GyrA and Glu84-Lys and His103-Tyr in GrlA; (ii) Ser-84Leu in GyrA, Ser52-Arg in GrlA, and Glu472-Val in GrlB; and (iii) Ser84-Leu in GyrA, Glu477-Val in GyrB, and Glu84-Lys and His103-Tyr in GrlA. Addition of the efflux pump inhibitor reserpine (10 μg/ml) resulted in 4- to 16-fold increases in the potencies of the NFQs against these mutants, whereas it resulted in 2-fold increases in the potencies of the NFQs against the parent.

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