scholarly journals Susceptibility of Candida dubliniensis to Salivary Histatin 3

2003 ◽  
Vol 47 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Deirdre H. Fitzgerald ◽  
David C. Coleman ◽  
Brian C. O'Connell
Keyword(s):  
Reference Strain ◽  
Therapeutic Potential ◽  
Oral Candidiasis ◽  
Human Saliva ◽  
Antifungal Drugs ◽  
Candida Dubliniensis ◽  
Immunodeficiency Virus ◽  
Fluconazole Resistant ◽  
Different Strains

ABSTRACT Candida dubliniensis is a recently described Candida species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected patients and patients with AIDS. The majority of C. dubliniensis clinical isolates tested to date are susceptible to the commonly used antifungal drugs, including fluconazole, ketoconazole, itraconazole, and amphotericin B. However, the appearance of fluconazole-resistant C. dubliniensis strains in this patient group is increasing. Histatins are a family of basic histidine-rich proteins present in human saliva which have therapeutic potential in the treatment of oral candidiasis. The mechanism of action of histatin is distinct from that of commonly used azole and polyene drugs. Characterization of the antifungal activity of histatin has mainly been carried out using C. albicans but it is also effective in killing C. glabrata and C. krusei. Here we report that C. dubliniensis is also susceptible to killing by histatin 3. The concentration of histatin 3 giving 50% killing (the IC50 value) ranged from 0.043 to 0.196 mg/ml among different strains of C. dubliniensis. The least-susceptible C. dubliniensis strain, P9224, was found to internalize histatin at a lower rate than the C. albicans reference strain CA132A. The dissociation constant (Kd ) for the least-susceptible strain (C. dubliniensis 9224) was ninefold higher than that for the C. albicans reference strain. These results suggest that histatin 3 may have potential as an effective antifungal agent, particularly in the treatment of oral candidiasis in HIV-infected patients and patients with AIDS in which resistance to the commonly used antifungal drug fluconazole has emerged.

scholarly journals Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro.

1997 ◽  
Vol 41 (3) ◽  
pp. 617-623 ◽  
Author(s):  
G P Moran ◽  
D J Sullivan ◽  
M C Henman ◽  
C E McCreary ◽  
B J Harrington ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amphotericin B ◽  
Oral Candidiasis ◽  
Antifungal Drugs ◽  
Candida Dubliniensis ◽  
Fluconazole Resistance ◽  
Immunodeficiency Virus ◽  
Fluconazole Resistant ◽  
Hiv Negative

Candida dubliniensis is a recently described species of Candida associated with oral candidiasis in human immunodeficiency virus (HIV)-infected individuals. Nineteen oral isolates of C. dubliniensis recovered from 10 HIV-positive and 4 HIV-negative individuals and one vaginal isolate from an additional HIV-negative subject were assessed for fluconazole susceptibility by broth microdilution (BMD), hyphal elongation assessment, and Etest. The susceptibilities of these 20 isolates to itraconazole and amphotericin B and of 10 isolates to ketoconazole were also determined by BMD only. Sixteen of the C. dubliniensis isolates were susceptible to fluconazole (MIC range, 0.125 to 1.0 microgram ml-1), and four (recovered from two AIDS patients) were fluconazole resistant (MIC range, 8 to 32 micrograms ml-1). Fluconazole susceptibility data obtained by hyphal elongation assessment correlated well with results obtained by BMD, but the corresponding Etest MIC results were one to four times higher. All of the isolates tested were found to be sensitive to itraconazole, ketoconazole, and amphotericin B. Sequential exposure of two fluconazole-sensitive (MIC, 0.5 microgram ml-1) C. dubliniensis isolates to increasing concentrations of fluconazole in agar medium resulted in the recovery of derivatives which expressed a stable fluconazole-resistant phenotype (BMD-determined MIC range, 16 to 64 micrograms ml-1), even after a minimum of 10 consecutive subcultures on drug-free medium and following prolonged storage at -70 degrees C. The clonal relationship between the parental isolates and their respective fluconazole-resistant derivatives was confirmed by genomic DNA fingerprinting and karyotype analysis. The results of this study demonstrate that C. dubliniensis is inherently susceptible to commonly used antifungal drugs, that fluconazole resistance does occur in clinical isolates, and that stable fluconazole resistance can be readily induced in vitro following exposure to the drug.

scholarly journals Detection and molecular characterization of kobuvirus from diarrheic goats in Minnesota

2020 ◽  
Vol 32 (6) ◽  
pp. 873-879
Author(s):  
Nader M. Sobhy ◽  
Aníbal G. Armién ◽  
Arno Wünschmann ◽  
Dean Muldoon ◽  
Sagar M. Goyal ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phylogenetic Analysis ◽  
Sanger Sequencing ◽  
Reference Strain ◽  
Whole Genome ◽  
Vp1 Gene ◽  
Pcr Products ◽  
Different Strains ◽  
Endemic State

Kobuvirus infections are common among humans, rodents, carnivores, pigs, and ruminants. We report herein the complete genome sequence of a novel caprine kobuvirus (MN604700) from diarrheic kids in Minnesota. Whole-genome sequencing revealed a kobuvirus genome of 8,139 nt with a single ORF region encoding a polyprotein of 2,480 amino acids. Further analysis revealed nt substitutions along the genome compared with that of the caprine kobuvirus reference strain, with 93% identity. Phylogenetic analysis indicated that the clade of the caprine kobuvirus was most closely related to porcine kobuviruses rather than bovine or ovine kobuviruses. Using primers designed from this genome, caprine kobuvirus was identified in the stools of other goats. Sanger sequencing of PCR products indicated 3D and VP1 gene nucleotides of this latter strain were 95% and 91% identical with those of MN604700, respectively. There were 35 and 101 nt substitutions in 3D and VP1 genes, respectively. Findings of kobuvirus over a 2-y period may indicate an endemic state, which needs further research. In addition, screening for kobuviruses over large geographic areas is needed to identify the evolutionary connections among different strains.

The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Yunchun Li ◽  
Haoxing Wu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Memory Loss ◽  
Related Research ◽  
Central Nervous System Disorders ◽  
G Protein Coupled

Abstract:: Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attentions were paid to the pathophysiology and therapeutic potential of purinergic signaling in central nervous system disorders. Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD follows a series of failures in recent years, more researchers focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, summaries the potential agents as modulators for the receptors of purinergic signaling in AD related research and treatments. Thus, our paper provided an insight for purinergic signaling in the development of anti-AD therapies.

Sign in / Sign up

Export Citation Format

Share Document