Azole and Echinocandin Resistance Mechanisms and Genotyping of Candid tropicalis in Japan: Cross-Boundary Dissemination and Animal-Human Transmission of C. tropicalis Infection

This study was designed to evaluate the prevalence of antifungal resistance, genetic mechanisms associated with in vitro induction of azole and echinocandin resistance and genotyping of Candida krusei , which is intrinsically resistant to fluconazole and is recovered from clinical and non-clinical sources from different countries. Our results indicated that all the isolates were susceptible or had the wild phenotype (WT) to azoles, amphotericin B, and only 1.27% showed non-WT for flucytosine. Although 70.88% of the isolates were resistant to caspofungin, none of them were categorized as echinocandin-resistant as all were susceptible to micafungin and no FKS1 hotspot 1 (HS1) or HS2 mutations were detected. In vitro induction of azole and echinocandin resistance confirmed the rapid development of resistance at low concentrations of fluconazole (4 μg/ml), voriconazole (0.06 μg/ml) and micafungin (0.03 μg/ml), with no difference between clinical and non-clinical isolates in the resistance development. Overexpression of ABC1 gene and FKS1 HS1 mutations were the major mechanisms responsible for azole and echinocandin resistance, respectively. Genotyping of our 79 isolates coupled with 217 other isolates from different sources and geography confirmed that the isolates belong to two main subpopulations, with isolates from human clinical material and Asia being more predominant in cluster 1, and environmental and animals isolates and those from Europe in cluster 2. Our results are of critical concern, since realizing that the C. krusei resistance mechanisms and their genotyping are crucial for guiding specific therapy and for exploring the potential infection source.

Download Full-text

Evaluation of CLSI M44-A2 Disk Diffusion and Associated Breakpoint Testing of Caspofungin and Micafungin Using a Well-Characterized Panel of Wild-Type andfksHot Spot Mutant Candida Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01373-10 ◽

2011 ◽

Vol 55 (5) ◽

pp. 1891-1895 ◽

Cited By ~ 13

Author(s):

Maiken Cavling Arendrup ◽

Steven Park ◽

Steven Brown ◽

Michael Pfaller ◽

David S. Perlin

Keyword(s):

Quality Control ◽

Hot Spot ◽

Resistance Mechanisms ◽

Disk Diffusion ◽

Antifungal Compounds ◽

Wild Type ◽

Content Type ◽

Disk Diffusion Testing ◽

Echinocandin Resistance ◽

Disk Testing

ABSTRACTDisk diffusion testing has recently been standardized by the CLSI, and susceptibility breakpoints have been established for several antifungal compounds. For caspofungin, 5-μg disks are approved, and for micafungin, 10-μg disks are under evaluation. We evaluated the performances of caspofungin and micafungin disk testing using a panel ofCandidaisolates with and without knownFKSechinocandin resistance mechanisms. Disk diffusion and microdilution assays were performed strictly according to CLSI documents M44-A2 and M27-A3. Eighty-nine clinicalCandidaisolates were included:Candida albicans(20 isolates/10 mutants),C. glabrata(19 isolates/10 mutants),C. dubliniensis(2 isolates/1 mutant),C. krusei(16 isolates/3 mutants),C. parapsilosis(14 isolates/0 mutants), andC. tropicalis(18 isolates/4 mutants). Quality control strains wereC. parapsilosisATCC 22019 andC. kruseiATCC 6258. The correlations between zone diameters and MIC results were good for both compounds, with identical susceptibility classifications for 93.3% of the isolates by applying the current CLSI breakpoints. However, the numbers offkshot spot mutant isolates misclassified as being susceptible (S) (very major errors [VMEs]) were high (61% for caspofungin [S, ≥11 mm] and 93% for micafungin [S, ≥14 mm]). Changing the disk diffusion breakpoint to S at ≥22 mm significantly improved the discrimination. For caspofungin, 1 VME was detected (aC. tropicalisisolate with an F76S substitution) (3.5%), and for micafungin, 10 VMEs were detected, the majority of which were forC. glabrata(8/10). The broadest separation between zone diameter ranges for wild-type (WT) and mutant isolates was seen for caspofungin (6 to 12 mm versus −4 to 7 mm). In conclusion, caspofungin disk diffusion testing with a modified breakpoint led to excellent separation between WT and mutant isolates for allCandidaspecies.

Download Full-text

Antifungal Susceptibility Profiles and Resistance Mechanisms of Clinical Diutina catenulata Isolates With High MIC Values

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.739496 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xin-Fei Chen ◽

Wei Zhang ◽

Xin Fan ◽

Xin Hou ◽

Xiao-Yu Liu ◽

...

Keyword(s):

Amino Acid ◽

Hot Spot ◽

Antifungal Susceptibility ◽

Resistance Mechanisms ◽

Flight Mass Spectrometry ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Echinocandin Resistance ◽

Ascomycete Yeast ◽

High Mics

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06–0.12 μg/ml), posaconazole (0.06–0.12 μg/ml), amphotericin B (0.25–1 μg/ml), and 5-flucytosine (range, <0.06–0.12 μg/ml), whereas four isolates showed high MICs (≥4 μg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.

Download Full-text

Resistance mechanisms ofPrunusrootstocks to root-knot nematode,Meloidogyne incognita

Fruits ◽

10.1051/fruits/2009024 ◽

2009 ◽

Vol 64 (5) ◽

pp. 295-303 ◽

Cited By ~ 1

Author(s):

Hang Ye ◽

Wen-jun Wang ◽

Guo-jie Liu ◽

Li-xin Zhu ◽

Ke-gong Jia

Keyword(s):

Meloidogyne Incognita ◽

Resistance Mechanisms ◽

Root Knot Nematode

Download Full-text

Emerging Antimicrobial Resistance Among Methicillin Resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Centre in North India

JMS SKIMS ◽

10.33883/jms.v23i1.747 ◽

2020 ◽

Vol 23 (1) ◽

pp. 48-49

Author(s):

Javaid Ahmad Bhat ◽

Shariq Rashid Masoodi

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Resistance ◽

Tertiary Care ◽

Resistance Mechanisms ◽

North India ◽

Global Public Health ◽

Care Centre ◽

Tertiary Care Centre ◽

Effective Prevention ◽

Mupirocin Resistance

Apropos to the article by Dr Bali, titled “Mupirocin resistance in clinical isolates of methicillin-sensitive and resistant Staphylococcus aureus in a tertiary care centre of North India” (1), the authors have raised important issue of emerging antimicrobial resistance (AMR). Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. As per WHO, AMR lurks the effective prevention and management of an ever-increasing spectrum of infections caused by bacteria, parasites, fungi and viruses. Novel resistance mechanisms are emerging and spreading globally, threatening the man’s ability to treat common infectious diseases.

Download Full-text

1 / Development of echinocandin resistance after in vitro micafungin exposure in clinical isolates of Candida glabrata

10.26226/morressier.5ac39997d462b8028d899dfe ◽

2018 ◽

Author(s):

O. Rivero-Menendez

Keyword(s):

Candida Glabrata ◽

Clinical Isolates ◽

Echinocandin Resistance

Download Full-text

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

10.26434/chemrxiv.7877987.v1 ◽

2019 ◽

Author(s):

Daniel Sun ◽

Soumya Poddar ◽

Roy D. Pan ◽

Juno Van Valkenburgh ◽

Ethan Rosser ◽

...

Keyword(s):

Solid Tumor ◽

Small Cell Lung Carcinoma ◽

Single Agent ◽

Resistance Mechanisms ◽

Tumor Models ◽

Cell Lung Carcinoma ◽

Adaptive Resistance ◽

Cancer Models ◽

Nanomolar Range

The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone HCT-13, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC90 values in the low-to-mid nanomolar range. We show that the cytotoxicity of HCT-13 is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following HCT-13 treatment. Taken together, HCT-13 is potent against solid tumor models and warrants in vivo evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

Download Full-text

5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

10.26434/chemrxiv.9759302.v1 ◽

2019 ◽

Author(s):

Bram Frohock ◽

Jessica M. Gilbertie ◽

Jennifer C. Daiker ◽

Lauren V. Schnabel ◽

Joshua Pierce

Keyword(s):

Staphylococcus Aureus ◽

Human Health ◽

Matrix Model ◽

Bacterial Load ◽

Collagen Matrix ◽

Resistance Mechanisms ◽

Novel Therapeutics ◽

Innovative Treatment ◽

Antibiotic Action ◽

Biofilm Infection

<div>The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div>

Download Full-text