Emerging Microbes & Infections
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2024
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IF 8.4
Yaqin Peng,Yue Liu,Xuegao Yu,Jingchun Fang,Zhaowang Guo,Kang Liao,Peisong Chen,Penghao Guo
Candida auris is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of C. auris candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All C. auris isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the ERG11 gene. The isolates with Clade I presented Y132F mutation in the ERG11 gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of C. auris candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of C. auris candidemia and colonization after the first positive bloodstream. C. auris colonization was still observed after the first C. auris candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of C. auris in Guangdong, highlighting great challenges in clinical prevention and control.
研究领域:
医学真菌学
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感染病学
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抗真菌药物研究
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高影响因子
MYCOSES
·
2026
·Vol. 69
·期 4
·e70176
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IF 3.4
Mingjing Wei,Jian Guo,Li Li,Junhao Zhu,Yuyuan Xue,Guo Chen,Fan Yang,Wenjuan Wu,Min Zhu
Background Candida auris is a globally emerging multidrug-resistant fungus. Its dissemination is driven by patient movement and asymptomatic carriers. However, molecular epidemiological studies linking imported cases to local strains in large metropolitan areas remain limited. Objectives To analyse the molecular epidemiology and resistance mechanisms of 33 clinical isolates in Shanghai and propose an integrated infection control strategy tailored to metropolitan healthcare settings. Methods Isolates from 19 patients were identified via MALDI-TOF MS and sequencing. Antifungal susceptibility and biofilm formation were assessed. Environmental contamination was evaluated using PCR. Whole-genome sequencing (WGS) was employed to identify resistance mutations and perform phylogenetic analysis. Results All 33 isolates were fluconazole-resistant. Resistance to amphotericin B and echinocandins was observed in 9 and 4 isolates, respectively. All echinocandin-resistant strains harboured the Fks1-S639F mutation. Phylogenetic analysis revealed that Clade III (South African clade) was the dominant lineage. Colonisation was concentrated in the urinary tract and inguinal regions, while bedside tables were identified as key environmental reservoirs. All strains exhibited strong biofilm-forming capacity. Conclusions ICU patients serve as primary reservoirs, with transmission driven by interregional movement. The distinct colonisation patterns and environmental hotspots provide specific targets for screening. Integrating PCR-based environmental monitoring with culture methods constitutes an effective strategy. These findings underscore the need for a standardised protocol integrating molecular diagnostics to optimise infection control in urban hospitals.
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高影响因子
Nature Microbiology
·
2026
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IF 18.7
Song Yabing,Chen Jinxin,Wan Junhua,Zhang Jiamo,Liu Qizheng,Sun Fei,Zhang Hanlin,Guo Yuru,Chow Eve W. L.,Chen Yali,Yan Ziyu,Wang Jianbin,Chen Kun,Wang Yue,Gao Jiaxin
Candida auris is an emerging fungal pathogen notable for its intrinsically high resistance to fluconazole, the most prescribed antifungal drug. However, the genetic regulators underlying fluconazole susceptibility in C. auris remain unclear. Here we performed a pooled screen of piggyBac ( PB ) transposition mutants and identified significant enrichment of mitochondrial genes whose inactivation reduces fluconazole susceptibility. A genome-wide genetic interaction analysis of a mitochondrial gene deletion mutant, pet309 Δ, suggests that the vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) is responsible for its reduced fluconazole susceptibility. Fluconazole induces significant upregulation of CDT1 through the calcineurin signalling pathway. Cdt1, beyond its canonical calcium-pumping function, has evolved another function in mediating fluconazole efflux through its fluconazole-induced, calcineurin- and ATP hydrolysis-dependent plasma membrane localization. In addition, Cdt1 accelerates the evolution of fluconazole resistance or tolerance, and its transcript levels are substantially elevated across resistant clinical isolates. Our findings reveal a neofunctionalized role for Cdt1 in mediating fluconazole efflux in C. auris .
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ARCHIVES OF MICROBIOLOGY
·
2024
·Vol. 206
·期 8
·1-26
·
IF 2.3
Li Can,Wang Jun,Li Hao,Wang Yemei,Wu Hui,Wei Wenfan,Wu Daqiang,Shao Jing,Wang Tianming,Wang Changzhong
Candida auris , a rapidly spreading multi-drug‐resistant fungus, is causing lethal infections under certain conditions globally. Baicalin (BE), an active ingredient extracted from the dried root of Scutellaria baicalensis Georgi, exhibits antifungal activity. However, studies have shown the distinctive advantages of Traditional Chinese medicine in combating fungal infections, while the effect of BE, an active ingredient extracted from the dried roots of Scutellaria baicalensis Georgi, on C. auris, remains unknown. Therefore, this study aims to evaluate the potential of BE as an antifungal agent against the emerging multidrug‐resistant C. auris . Various assays and models, including microbroth dilution, time growth curve analysis, spot assays, adhesion tests, flocculation test, cell surface hydrophobicity assay, hydrolase activity assays, XTT assay, violet crystal assay, scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), flow cytometry, Live/dead fluorescent staining, reactive oxygen species (ROS), cell wall assay, aggregation assay, porcine skin model, Galleria mellonella larvae ( G. mellonella larvae) infection model, and reverse transcription–quantitative polymerase chain reaction (RT-PCR) were utilized to investigate how baicalein suppresses C. auris through possible multifaceted mechanisms. The findings indicate that BE strongly inhibited C. auris growth, adhesion, and biofilm formation. It also effectively reduced drug resistance and aggregation by disrupting the cell membrane and cell wall while reducing colonization and invasion of the host. Transcriptome analysis showed significant modulation in gene expression related to different virulence factors post‐BE treatment. In conclusion, BE exhibits significant effectiveness against C. auris , suggesting its potential as a viable treatment option due to its multifaceted suppression mechanisms. Graphical abstract Schematic representation of this study. Baicalein (BE) can effectively hinder the growth and colonization of C. auris by disrupting the expression of multiple virulence factors. This results in a strong antifungal effect, providing protection to the host from infection.
研究领域:
微生物学
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药理学
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分子生物学
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传染病学
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Xiaohui Yang,Jie Li,Yilang Zhong,Yuanjiayi Shen,Chenqin Xu,Zhouyu Nie,He Wang,Rui Cao,Miaomiao Wang,Jinyu Zhang,Chao Ma,Tongkai Cai,Chenglin Jia,Ruilian Wang,Hao Yin,Jian Chen,Yongbing Cao
Background Candida auris ( C. auris ) is an emerging multidrug-resistant fungal pathogen. Current antifungals are often insufficient, creating a need for host-directed strategies. Sirtuin 3 (SIRT3) is a mitochondrial deacetylase that regulates redox homeostasis, but its role in antifungal macrophage defense is not well defined. We examined how SIRT3 shapes macrophage responses to C. auris . We also evaluated ethyl caffeate (EC) as a host-directed modulator. Methods We used murine macrophages with Sirt3 knockdown or overexpression. We quantified phagocytosis, intracellular fungal survival, mitochondrial ROS dynamics, and macrophage cell integrity using imaging, flow cytometry, CFU assays, and LDH release. We profiled infection-induced transcriptional programs by RNA-seq and performed pathway analyses. We tested EC both in vitro and in systemic infection models in Drosophila and mice. We assessed pathway markers by immunoblotting and immunofluorescence. We used the SIRT3 inhibitor 3-TYP to test inhibition sensitivity. Results SIRT3 deficiency impaired macrophage antifungal function and was accompanied by redox imbalance. mtROS regulation was disrupted in a biphasic pattern, with an early spike followed by late depletion. Transcriptomics linked SIRT3-dependent programs to FOXO and PI3K–AKT signaling. In macrophages, SIRT3 status tracked with FOXO3A acetylation and AKT phosphorylation. EC showed weak direct antifungal activity in vitro but improved outcomes in systemic infection models. EC treatment increased SIRT3 abundance and was associated with reduced FOXO3A acetylation and restrained infection-associated AKT activation. These functional and signaling effects were largely sensitive to SIRT3 inhibition by 3-TYP. Conclusion This study connects SIRT3-dependent redox control to FOXO3A–AKT signaling during C. auris infection. It also supports EC as a host-directed candidate that improves antifungal defense in vivo while limiting inflammatory injury.
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高影响因子
BIOFOULING
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2020
·
IF 2.351
Juanjuan Liu,Qianqian Li,Changzhong Wang,Jing Shao,Tianming Wang,Daqiang Wu,Kelong Ma,Guiming Yan,Dengke Yin
Traditional herbal monomers (THMs) are widely distributed in many traditional Chinese formulas (TCFs) and decoctions (TCDs) and are frequently used for the prevention and treatment of fungal infections. The antifungal activities of five common THMs, including sodium houttuyfonate (SH), berberine (BER), palmatine (PAL), jatrorrhizine (JAT) and cinnamaldehyde (CIN), and their potential for inducing cell wall remodeling (CWR), were evaluated against Candida albicans SC5314 and Candida auris 12372. SH/CIN plus BER/PAL/JAT showed synergistic antifungal activity against both Candida isolates. Furthermore, SH-associated combinations (SH plus BER/PAL/JAT) induced stronger exposure of β-glucan and chitin than their counterparts, while CIN triggered more marked exposure compared with CIN-associated combinations (CIN plus BER/PAL/JAT). Collectively, this study demonstrated the anti-Candida effect and the CWR induction potential of the five THMs and their associated combinations, providing a possibility of their in vivo application against fungal-associated infections.
研究领域:
药理学
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微生物学
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中医药
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高影响因子
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