scholarly journals Candida auris: A Quick Review on Identification, Current Treatments, and Challenges

2021 ◽  
Vol 22 (9) ◽  
pp. 4470
Author(s):  
Lucia Černáková ◽  
Maryam Roudbary ◽  
Susana Brás ◽  
Silva Tafaj ◽  
Célia F. Rodrigues
Keyword(s):  
Multidrug Resistance ◽  
Alternative Treatment ◽  
Fungal Pathogen ◽  
Fungal Diseases ◽  
High Rate ◽  
The Novel ◽  
Mechanisms Of Resistance ◽  
Candida Auris ◽  
Natural And Synthetic

Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported.

scholarly journals Genome-Wide Analysis of Experimentally Evolved Candida auris Reveals Multiple Novel Mechanisms of Multidrug Resistance

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Hans Carolus ◽  
Siebe Pierson ◽  
José F. Muñoz ◽  
Ana Subotić ◽  
Rita B. Cruz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Fungal Pathogen ◽  
Hot Spot ◽  
Novel Mutations ◽  
Candida Auris ◽  
Content Type ◽  
Genome Wide ◽  
High Concern

ABSTRACT Candida auris is globally recognized as an opportunistic fungal pathogen of high concern, due to its extensive multidrug resistance (MDR). Still, molecular mechanisms of MDR are largely unexplored. This is the first account of genome-wide evolution of MDR in C. auris obtained through serial in vitro exposure to azoles, polyenes, and echinocandins. We show the stepwise accumulation of copy number variations and novel mutations in genes both known and unknown in antifungal drug resistance. Echinocandin resistance was accompanied by a codon deletion in FKS1 hot spot 1 and a substitution in FKS1 “novel” hot spot 3. Mutations in ERG3 and CIS2 further increased the echinocandin MIC. Decreased azole susceptibility was linked to a mutation in transcription factor TAC1b and overexpression of the drug efflux pump Cdr1, a segmental duplication of chromosome 1 containing ERG11, and a whole chromosome 5 duplication, which contains TAC1b. The latter was associated with increased expression of ERG11, TAC1b, and CDR2 but not CDR1. The simultaneous emergence of nonsense mutations in ERG3 and ERG11 was shown to decrease amphotericin B susceptibility, accompanied with fluconazole cross-resistance. A mutation in MEC3, a gene mainly known for its role in DNA damage homeostasis, further increased the polyene MIC. Overall, this study shows the alarming potential for and diversity of MDR development in C. auris, even in a clade until now not associated with MDR (clade II), stressing its clinical importance and the urge for future research. IMPORTANCE Candida auris is a recently discovered human fungal pathogen and has shown an alarming potential for developing multi- and pan-resistance toward all classes of antifungals most commonly used in the clinic. Currently, C. auris has been globally recognized as a nosocomial pathogen of high concern due to this evolutionary potential. So far, this is the first study in which the stepwise progression of multidrug resistance (MDR) in C. auris is monitored in vitro. Multiple novel mutations in known resistance genes and genes previously not or vaguely associated with drug resistance reveal rapid MDR evolution in a C. auris clade II isolate. Additionally, this study shows that in vitro experimental evolution can be a powerful tool to discover new drug resistance mechanisms, although it has its limitations.

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

Activity of ceftazidime•avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance

2017 ◽  
Vol 35 (8) ◽  
pp. 497-502
Author(s):  
Inmaculada López-Hernández ◽  
Noemí Alonso ◽  
Marta Fernández-Martínez ◽  
Laura Zamorano ◽  
Alba Rivera ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Mechanisms Of Resistance

scholarly journals SARS-CoV-2: preliminary study of infected human nasopharyngeal tissue by high resolution microscopy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Brian Mondeja ◽  
Odalys Valdes ◽  
Sonia Resik ◽  
Ananayla Vizcaino ◽  
Emilio Acosta ◽  
...  
Keyword(s):  
High Resolution ◽  
Control Sample ◽  
Negative Control ◽  
High Rate ◽  
Apical Region ◽  
The Novel ◽  
Rt Pcr ◽  
Crown Shape ◽  
Novel Coronavirus ◽  
High Resolution Microscopy

Abstract Background The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published. Methods Nasopharyngeal swabs were collected from 12 Cuban individuals, six asymptomatic and RT-PCR negative (negative control) and six others from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by scanning electron microscopy (SEM), confocal microscopy (CM) and, atomic force microscopy. Improvement and segmentation of coronavirus images were performed by a novel mathematical image enhancement algorithm. Results The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions budding through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by SEM. Viral antigen was identified in the apical cells zone by CM. Conclusions The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to nasopharyngeal samples awaits future use.

scholarly journals Prevalence and molecular characterization of extended spectrum beta-lactamase producing uropathogenic Escherichia coli in a tertiary health care facility in Anambra State, Nigeria

2021 ◽  
Vol 11 (3) ◽  
pp. 300-311
Author(s):  
Ifeoma G Nwafuluaku ◽  
Nneka R Agbakoba ◽  
Simon N Ushie ◽  
Eucharia A Dilibe
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Care Facility ◽  
Health Care Facility ◽  
High Rate ◽  
Esbl Production ◽  
Extended Spectrum Beta Lactamase ◽  
Anambra State ◽  
Amoxicillin Clavulanate ◽  
Synergy Test

Background: The prevalence of ESBLs-producing Escherichia coli has recently increased worldwide due to the expression of ESBL genes which had led to high rate of multidrug resistance antibiotics. Aim: To determine the antimicrobial susceptibility patterns of E. coli isolates and evaluating the ESBL carriage of these isolates at phenotypic and genotypic levels. Methods: One hundred and two clinical Escherichia coli isolates were recovered from UTI suspects and analyzed for ESBL production at phenotypic and genotypic levels using Modified Double Disc Synergy Test and Polymerase Chain Reaction respectively. Results: Of the 102 isolates, 100(98.04%) were associated with MDR phenotypes. The isolates showed variable resistance to all the antibiotics used in the study. The resistance rates were 99.0%, 97.1%, 88.2%, 82.4%, 81.4%, 65.7%, 54.9%, 46.1%, 46.1%, 23.5% for ampicillin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, ceftazidime, amoxicillin-clavulanate, gentamycin, cefoxitin, nitrofurantoin and imipenem, and respectively. The prevalence of phenotypic ESBL production was 74.5%. Based on the PCR results, the randomly selected 20 ESBL-positive isolates possessed one or more ESBLs genes. CTX-M type was the predominant ESBLs type (100%), while those for TEM and SHV-types were 85% and 80% respectively. Four genotype patterns were detected (CTX-M, TEM+CTX-M, SHV+CTX-M and SHV+TEM+CTX-M). The genotype SHV+TEM+CTX-M, was the predominant (70%), followed by the genotype TEM +CTX-M combination (15%). The occurrences of the genotypes, CTX-M and SHV+CTX-M were 5% and 10% respectively. Conclusion: This study found a high rate of Phenotypic ESBL production (74.5%) among the isolates with multidrug resistance, CTX-M as the predominant ESBLs type (100%) and combination of SHV+TEM+CTX-M as the predominant genotype (70%).

scholarly journals Salmonella enterica Serovar Typhi Strains Isolated in Korea Containing a Multidrug Resistance Class 1 Integron

2003 ◽  
Vol 47 (6) ◽  
pp. 2006-2008 ◽  
Author(s):  
Hyunjoo Pai ◽  
Jeong-hum Byeon ◽  
Sunmi Yu ◽  
Bok Kwon Lee ◽  
Shukho Kim
Keyword(s):  
Multidrug Resistance ◽  
Resistance Genes ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Conjugative Plasmid ◽  
The Novel ◽  
Class 1 Integron ◽  
Salmonella Enterica Serovar Typhi ◽  
Class 1 ◽  
Clonal Spread

ABSTRACT Six strains of Salmonella enterica serovar Typhi which were resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, streptomycin, tetracycline, and gentamicin were isolated in Korea. This multidrug resistance was transferred by a conjugative plasmid of about 50 kb. The plasmid harbored a class 1 integron, which included six resistance genes, aacA4b, catB8, aadA1, dfrA1, aac(6′)-IIa, and the novel blaP2, in that order. All of the isolates showed the same-size plasmids and the same ribotyping patterns, which suggests a clonal spread of these multidrug-resistant isolates.

scholarly journals Effect of a Novel Patient Garment on Perceived Privacy during Colonoscopy: A Simple Approach to Minimize Embarrassment

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Ali Aamar ◽  
Zeeshan Butt ◽  
Kamraan Madhani ◽  
Iqra Hussain ◽  
Joel Garsten ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
The United States ◽  
Simple Approach ◽  
High Rate ◽  
The Novel ◽  
Screening Programs ◽  
Before And After ◽  
Repeat Colonoscopy ◽  
Acceptance Rates ◽  
Study Participants

Background. In the United States, patients wear a one-piece, reusable cloth gown during colonoscopy procedures. Many patients report embarrassment related to bodily exposure during colonoscopy. This may limit participation in colorectal cancer screening programs. Aims. To assess whether the use of a novel, disposable patient garment (Privacy Pants, Jackson, MS), which increases patient coverage, can reduce embarrassment related to bodily exposure and increase colonoscopy acceptance rates. Methods. Patients were offered a novel gown, and they completed questionnaires before and after colonoscopy. Results. A total of 120 patients participated. 54% were female and 82% were Caucasian. The novel gown had high overall satisfaction (8.3) and was associated with a sense of respect during the procedure (9.4). 67% (80) of the patients had a prior colonoscopy, and of these, 76% would request a novel gown over a traditional gown for future procedures. Among all study participants, a high rate of acceptability for repeat colonoscopy if recommended by their doctors was reported (mean of 9.4). Nonwhites were more likely to have a concern for embarrassment addressed by using novel gowns as compared to whites (P value 0.02). Conclusion. All participants, particularly women and nonwhite participants, reported high rates of respect and satisfaction and decrease in embarrassment utilizing the novel gown during colonoscopy. Patients who had prior colonoscopy with a traditional gown preferred the novel garment. A novel procedure gown may enhance colonoscopy acceptance by minimizing embarrassment.

scholarly journals The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Rosie Jaramillo ◽  
Marcos Olivo ◽  
Hoja Patterson ◽  
...  
Keyword(s):  
The Novel ◽  
Candida Auris ◽  
Once Daily ◽  
Content Type ◽  
Fungal Burden

ABSTRACT The in vitro and in vivo activity of the arylamidine T-2307 against Candida auris was evaluated. T-2307 demonstrated in vitro activity (MIC ranges ≤ 0.008 to 0.015 μg/ml at 50% inhibition; 0.125 to >4 μg/ml at 100% inhibition). Treatment with T-2307 (3 mg/kg subcutaneous [SC] once daily) also significantly improved survival (70% at 21 days postinfection) and reduced kidney fungal burden (5.06 log10 CFU/g) compared to control (0% survival and 7.09 log10 CFU/g) (P < 0.01).

scholarly journals Recent Advances in Genetic Tools for Acinetobacter baumannii

2020 ◽  
Vol 11 ◽  
Author(s):  
Ellen M. E. Sykes ◽  
Soumya Deo ◽  
Ayush Kumar
Keyword(s):  
Multidrug Resistance ◽  
Acinetobacter Baumannii ◽  
Genetic Manipulation ◽  
World Health ◽  
Mechanisms Of Resistance ◽  
Genetic Manipulations ◽  
The World ◽  
Reporter Systems ◽  
Health Organization ◽  
Susceptibility Profiles

Acinetobacter baumannii is classified as a top priority pathogen by the World Health Organization (WHO) because of its widespread resistance to all classes of antibiotics. This makes the need for understanding the mechanisms of resistance and virulence critical. Therefore, tools that allow genetic manipulations are vital to unravel the mechanisms of multidrug resistance (MDR) and virulence in A. baumannii. A host of current strategies are available for genetic manipulations of A. baumannii laboratory-strains, including ATCC® 17978TM and ATCC® 19606T, but depending on susceptibility profiles, these strategies may not be sufficient when targeting strains newly obtained from clinic, primarily due to the latter’s high resistance to antibiotics that are commonly used for selection during genetic manipulations. This review highlights the most recent methods for genetic manipulation of A. baumannii including CRISPR based approaches, transposon mutagenesis, homologous recombination strategies, reporter systems and complementation techniques with the spotlight on those that can be applied to MDR clinical isolates.

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