scholarly journals Increase of Virulence and Its Phenotypic Traits in Drug-Resistant Strains of Candida albicans

2008 ◽  
Vol 52 (3) ◽  
pp. 927-936 ◽  
Author(s):  
Letizia Angiolella ◽  
Anna Rita Stringaro ◽  
Flavia De Bernardis ◽  
Brunella Posteraro ◽  
Mariantonietta Bonito ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Biological Properties ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Phenotypic Traits ◽  
Homozygous Mutation ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT There is concern about the rise of antifungal drug resistance, but little is known about comparative biological properties and pathogenicity of drug-resistant strains. We generated fluconazole (FLC; CO23RFLC)- or micafungin (FK; CO23RFK)-resistant strains of Candida albicans by treating a FLC- and FK-susceptible strain of this fungus (CO23S) with stepwise-increasing concentrations of either drug. Molecular analyses showed that CO23RFLC had acquired markedly increased expression of the drug-resistance efflux pump encoded by the MDR1 gene, whereas CO23RFK had a homozygous mutation in the FSK1 gene. These genetic modifications did not alter to any extent the growth capacity of the drug-resistant strains in vitro, either at 28°C or at 37°C, but markedly increased their experimental pathogenicity in a systemic mouse infection model, as assessed by the overall mortality and target organ invasion. Interestingly, no apparent increase in the vaginopathic potential of the strains was observed with an estrogen-dependent rat vaginal infection. The increased pathogenicity of drug-resistant strains for systemic infection was associated with a number of biochemical and physiological changes, including (i) marked cellular alterations associated with a different expression and content of major cell wall polysaccharides, (ii) more rapid and extensive hypha formation in both liquid and solid media, and (iii) increased adherence to plastic and a propensity for biofilm formation. Overall, our data demonstrate that experimentally induced resistance to antifungal drugs, irrespective of drug family, can substantially divert C. albicans biology, affecting in particular biological properties of potential relevance for deep-seated candidiasis.

scholarly journals Synergistic Antifungal Activity of Chitosan with Fluconazole against Candida albicans, Candida tropicalis, and Fluconazole-Resistant Strains

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5114
Author(s):  
Wei-Hsuan Lo ◽  
Fu-Sheng Deng ◽  
Chih-Jung Chang ◽  
Ching-Hsuan Lin
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Candida Tropicalis ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Combinational Treatment ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

(1) Background: Few antifungal drugs are currently available, and drug-resistant strains have rapidly emerged. Thus, the aim of this study is to evaluate the effectiveness of the antifungal activity from a combinational treatment of chitosan with a clinical antifungal drug on Candida albicans and Candida tropicalis. (2) Methods: Minimum inhibitory concentration (MIC) tests, checkerboard assays, and disc assays were employed to determine the inhibitory effect of chitosan with or without other antifungal drugs on C. albicans and C. tropicalis. (3) Results: Treatment with chitosan in combination with fluconazole showed a great synergistic fungicidal effect against C. albicans and C. tropicalis, but an indifferent effect on antifungal activity when challenged with chitosan-amphotericin B or chitosan-caspofungin simultaneously. Furthermore, the combination of chitosan and fluconazole was effective against drug-resistant strains. (4) Conclusions: These findings provide strong evidence that chitosan in combination with fluconazole is a promising therapy against two Candida species and its drug-resistant strains.

scholarly journals Antifungal activity of MAF-1A peptide against Candida albicans

2021 ◽  
Author(s):  
Rong Cheng ◽  
Qiang Xu ◽  
Fangfang Hu ◽  
Hongling Li ◽  
Bin Yang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Membrane ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Fluorescent Staining ◽  
Qrt Pcr ◽  
Major Threat ◽  
Antifungal Action ◽  
Resistant Strains ◽  
Drug Resistant Strains

AbstractInvasive candidiasis is a major threat to human health, and Candida albicans is the most common pathogenic species responsible for this condition. The incidence of drug-resistant strains of C. albicans is rising, necessitating the development of new antifungal drugs. Antimicrobial peptides (AMPs) have recently attracted attention due to their unique ability to evade the drug resistance of microorganisms. However, the mechanism of their activity has not yet been identified. The current study analyzed the mode of action of MAF-1A by confocal microscopy, scanning electron microscopy, fluorescent staining, flow cytometry, and qRT-PCR. The results indicate that MAF-1A disrupts the cell membrane of C. albicans and enters the cell where it binds and interacts with nucleic acids. qRT-PCR demonstrated that the expression of several sterol biosynthesis–related genes in C. albicans was increased after MAF-1A treatment. Together, these findings suggest that MAF-1A exerts antifungal action by affecting both the cell membrane and intracellular components. The antifungal mechanism of MAF-1A is unique, and its identification has great research and clinical significance.

scholarly journals Accuracy of an amplicon-sequencing nanopore approach to identify variants in tuberculosis drug-resistance-associated genes

2021 ◽  
Vol 7 (12) ◽  
Author(s):  
Carla Mariner-Llicer ◽  
Galo A. Goig ◽  
Laura Zaragoza-Infante ◽  
Manuela Torres-Puente ◽  
Luis Villamayor ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Type Species ◽  
Variant Calling ◽  
Targeted Sequencing ◽  
Clinical Samples ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type ◽  
Resistant Strains ◽  
Drug Resistant Strains

A rapid and accurate diagnostic assay represents an important means to detect Mycobacterium tuberculosis , identify drug-resistant strains and ensure treatment success. Currently employed techniques to diagnose drug-resistant tuberculosis include slow phenotypic tests or more rapid molecular assays that evaluate a limited range of drugs. Whole-genome-sequencing-based approaches can detect known drug-resistance-conferring mutations and novel variations; however, the dependence on growing samples in culture, and the associated delays in achieving results, represents a significant limitation. As an alternative, targeted sequencing strategies can be directly performed on clinical samples at high throughput. This study proposes a targeted sequencing assay to rapidly detect drug-resistant strains of M. tuberculosis using the Nanopore MinION sequencing platform. We designed a single-tube assay that targets nine genes associated with drug resistance to seven drugs and two phylogenetic-determining regions to determine strain lineage and tested it in nine clinical isolates and six sputa. The study’s main aim is to calibrate MinNION variant calling to detect drug-resistance-associated mutations with different frequencies to match the accuracy of Illumina (the current gold-standard sequencing technology) from both culture and sputum samples. After calibrating Nanopore MinION variant calling, we demonstrated 100% agreement between Illumina WGS and our MinION set up to detect known drug resistance and phylogenetic variants in our dataset. Importantly, other variants in the amplicons are also detected, decreasing the recall. We identify minority variants and insertions/deletions as crucial bioinformatics challenges to fully reproduce Illumina WGS results.

scholarly journals Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China

2021 ◽  
Author(s):  
Rashmi S Mudliar ◽  
Umay Kulsum ◽  
Syed Beenish Rufai ◽  
Mika Umpo ◽  
Moi Nyori ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Resistant ◽  
Second Line ◽  
Arunachal Pradesh ◽  
Tuberculosis Programme ◽  
Indian State ◽  
Northeastern State ◽  
Resistant Strains ◽  
Drug Resistant Strains

Uncontrolled transmission of Mycobacterium tuberculosis (M. tuberculosis, MTB) drug resistant strains is a challenge to control efforts of global tuberculosis programme. Due to increasing multi-drug resistant (MDR) cases in Arunachal Pradesh, a northeastern state of India, the tracking and tracing of these resistant MTB strains is crucial for infection control and spread of drug resistance. This study aims to correlate the phenotypic DST, genomic DST (gDST) and phylogenetic analysis of MDR-MTB strains in the region. Of total 200 suspected MDR-MTB isolates, 125(62.5%) were identified as MTB. MGIT-960 SIRE DST detected 71/125(56.8%) isolates as MDR/RR-MTB of which 22(30.9%) were detected resistant to second line drugs. Whole genome sequencing of 65 isolates and their gDST found Ser315Thr mutation in katG (35/45;77.8%) and Ser531Leu mutation in rpoB (21/41;51.2%) associated with drug resistance. SNP barcoding categorized the dataset with Lineage2 (41;63.1%) being predominant followed by Lineage3 (10;15.4%), Lineage1 (8;12.3%) and Lineage4 (6;9.2%) respectively. Phylogenetic assignment by cgMLST gave insights of two Beijing sub-lineages viz; 2.2.1 (SNP difference < 19) and 2.2.1.2 (SNP difference < 9) associated with recent ongoing transmission in Arunachal Pradesh. This study provides first insight in identifying the ongoing transmission of two virulent Beijing sub-lineages associated with TB drug resistance.

Activities of tubercular inflammation (on the morphological data) with different duration in the patients with drug-resistant pulmonary tuberculosis

2016 ◽  
Vol 10 (1) ◽  
pp. 0-0
Author(s):  
Елипашев ◽  
A. Elipashev ◽  
Никольский ◽  
V. Nikolskiy ◽  
Шпрыков ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Sensitivity ◽  
Morphological Data ◽  
Control Group ◽  
Drug Resistant ◽  
Specific Therapy ◽  
Resistant Tuberculosis ◽  
Number Of Patients ◽  
Resistant Strains ◽  
Drug Resistant Strains

The purpose of this research was to determine the dependence of the tubercular inflammation activity of varying duration of the disease and drug resistance. Morphological activity of inflammation in 161 patients with drug-resistant and 149 patients with retaining its high sensitivity was studied. Morphological assessment of the activity of specific changes in tuberculosis was carried out according to the B.M. Ariel classification (1998). It was revealed at morphologic study of resection material that the greatest activity of specific inflammation and its prevalence outside the main lesion was in the group of patients limited with drug resistance tuberculosis. It was noted the prevalence of IV-V degree of morphological activity of tubercular process in the study group by 3 times over the control group with disease duration of more than 1 year. Predominance of widespread active specific changes (IV degree) was determined in 2 times for the first educed patients of basic group with drug-resistant above a control group. This is due to increasing the number of patients with cavernous and fibro-cavernous tuberculosis.Thus, it is necessary to operate patients with drug-resistant tuberculosis as soon as possi-ble after adequate specific therapy and the presence of the signs of stabilization process, because as the full stabilization of tuberculosis process did not achieve according to the morphological study of surgical specimens in the preoperative period. Further specific therapy becomes futile due to the rise of drug resistance, the emer-gence of new drug-resistant strains of Mycobacterium tuberculosis.

Transferred drug-resistance in Eimeria maxima

Parasitology ◽  
1975 ◽  
Vol 71 (3) ◽  
pp. 385-392 ◽  
Author(s):  
L. P. Joyner ◽  
C. C. Norton
Keyword(s):  
Drug Resistance ◽  
The Other ◽  
Drug Resistant ◽  
Resistance Factors ◽  
Eimeria Maxima ◽  
Series Of Experiments ◽  
Resistant Strains ◽  
Drug Resistant Strains

A series of experiments is described in which two drug-resistant strains of Eimeria maxima were passaged together in untreated chicks. The resultant oocysts were then inoculated into chicks treated with both drugs. When strains resistant to methyl benzoquate and sulphaquinoxaline or clopidol and sulphaquinoxaline were used the resultant infections were not controlled by the double treatment, indicating the acquisition of resistance factors by one strain from the other. When strains resistant to clopidol and methyl benzoquate were used the phenomenon was not observed.

scholarly journals Change of drug resistance patterns and genetic properties of R plasmids inSalmonella typhimuriumof bovine origin isolated from 1970 to 1979 in northern Japan

1981 ◽  
Vol 87 (2) ◽  
pp. 257-269 ◽  
Author(s):  
S. Makino ◽  
N. Ishiguro ◽  
G. Sato ◽  
N. Seno
Keyword(s):  
Drug Resistance ◽  
Mercury Resistance ◽  
Drug Resistant ◽  
Fertility Inhibition ◽  
Resistance Patterns ◽  
Clonal Distribution ◽  
R Plasmids ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Northern Japan

SummaryA total of 321Salmonella typhimuriumstrains of bovine origin obtained in northern Japan during the period 1970–1979 were tested for drug resistance and detection of conjugative R plasmids. Three hundred and eighteen (99·1 %) of these strains were resistant to one or more drugs. The isolation frequency of multiply drug-resistant strains tended to increase year by year. Two hundred and thirty-seven (74·5%) of these resistant strains carried conjugative R plasmids. A total of 308 R plasmids including 174 (56·5 %) thermosensitive (ts) R plasmids were derived from the 237 drug-resistant strains, indicating that 71 (30·0%) strains have two different conjugative R plasmids in a single host cell. Of the 308 R plasmids examined for fertility inhibition (fi), 167 ts and 131 non-ts R plasmids werefi−. Of the 60 ts R plasmids examined for incompatibility, 50 were classified into H1 group and 10 into H2 group. Of the 52 non-ts R plasmids examined, 35 were classified into the Iα group and the remaining plasmids were untypable in our tests. Mercury resistance marker was found in about 20% of H1 R plasmids coding for multiresistance, and all of H2 R plasmids coded for resistance to tellurite. The clonal distribution of anS. typhimuriumstrain which carried an H1 R plasmid coding for resistance to six drugs and mercury was recognized in 1978 and 1979.

scholarly journals Candida albicans Zinc Cluster Protein Upc2p Confers Resistance to Antifungal Drugs and Is an Activator of Ergosterol Biosynthetic Genes

2005 ◽  
Vol 49 (5) ◽  
pp. 1745-1752 ◽  
Author(s):  
Sarah MacPherson ◽  
Bassel Akache ◽  
Sandra Weber ◽  
Xavier De Deken ◽  
Martine Raymond ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biosynthetic Pathway ◽  
Fungal Species ◽  
Antifungal Drugs ◽  
Zinc Cluster ◽  
Expression Of Genes ◽  
Ergosterol Synthesis ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT The human pathogen Candida albicans is responsible for a large proportion of infections in immunocompromised individuals, and the emergence of drug-resistant strains is of medical concern. Resistance to antifungal azole compounds is often due to an increase in drug efflux or an alteration of the pathway for synthesis of ergosterol, an important plasma membrane component in fungi. However, little is known about the transcription factors that mediate drug resistance. In Saccharomyces cerevisiae, two highly related transcriptional activators, Upc2p and Ecm22p, positively regulate the expression of genes involved in ergosterol synthesis (ERG genes). We have identified a homologue in C. albicans of the S. cerevisiae UPC2/ECM22 genes and named it UPC2. Deletion of this gene impaired growth under anaerobic conditions and rendered cells highly susceptible to the antifungal drugs ketoconazole and fluconazole. Conversely, overexpression of Upc2p increased resistance to ketoconazole, fluconazole, and fluphenazine. Azole-induced expression of the ERG genes was abolished in a Δupc2 strain, while basal levels of these mRNAs remained unchanged. Importantly, the purified DNA binding domain of Upc2p bound in vitro to putative sterol response elements in the ERG2 promoter, suggesting that Upc2p increases the expression of the ERG genes by directly binding to their promoters. These results provide an important link between changes in the ergosterol biosynthetic pathway and azole resistance in this opportunistic fungal species.

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