Advanced Science
·
2023
·
IF 15.1
Ming-Yu Wu,Xiaoyu Xu,Rui Hu,Qingrong Chen,Luojia Chen,Yuncong Yuan,Jie Li,Li Zhou,Shun Feng,Lianrong Wang,Shi Chen,Meijia Gu
Candida albicans ( C. albicans ), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane-targeted aggregation-induced emission (AIE) photosensitizer (PS), TBTCP-QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP-QY has a high molar absorption coefficient and an excellent ability to generate 1 O 2 and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP-QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion ( ALS3 , EAP1 , and HWP1 ), invasion ( SAP1 and SAP2 ), and drug resistance ( MDR1 ) of C. albicans , which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP-QY-mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole-resistant strains. Moreover, TBTCP-QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.
研究领域:
微生物学
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药理学
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免疫学
·
传染病学
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Ledan Wang,Yijing Lin,Shuangshuang Liu,Chenjie Jin,Yunxuan Huang,Hui Liang,Xueying Sun,Kexin Zhang,Hanxing Chen,Xufei Zhang,Fang Wang,Zhenkun Lin,Linzhi Yan,Mengchun Chen,Deli Zhuge,Yijie Chen
Recurrent vulvovaginal candidiasis (RVVC) is an opportunistic infection predominantly caused by Candida albicans (C. albicans) and is particularly prevalent among individuals on immunosuppressants. Currently, there are no FDA-approved therapies for specifically controlling RVVC, mainly due to the need for therapeutics against RVVC that require both antifungal treatments to resolve active infections and strategies to prevent recurrence. This study introduces a biomimetic photoimmunotherapeutic nanoplatform consisting of an adjuvant-encapsulated polymeric core stabilized by a photosensitizer-loaded vaginal epithelial cell membrane coating to treat and protect against RVVC. With its cell membrane camouflaging, the nanoplatforms target and enhance adherence to the intravaginal site of C. albicans infection, allowing the nanoplatform to resist being flushed away by vaginal fluids. Upon subsequent near-infrared irradiation, the nanoplatform’s targeted photothermal power effectively eliminates C. albicans while minimizing thermal damage to surrounding healthy tissue. Postphotothermal treatment, the generated C. albicans-based debris and candidalysin-captured nanoplatform (serving as a nanotoxoid), along with adjuvant, are processed by resident antigen-presenting cells to promote multiantigenic immunity. This response provides protection against secondary intravaginal C. albicans infection (RVVC model) and C. albicans-induced systemic infection even under immunosuppressive conditions (septicemia model). Notably, anti-C. albicans antibodies produced in the pretreated mice exhibit comparable affinity to clinically isolated C. albicans strains, indicating potential for clinical application. Overall, this study underscores the potential of the proposed photoimmunotherapeutic nanoplatform for the effective treatment and prevention of RVVC.
研究领域:
医学
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微生物学
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免疫学
·
纳米医学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Yangyang Liu,Ruilian Li,Yuchen Zhang,Siming Jiao,Tong Xu,Yuhang Zhou,Yujing Wang,Jinhua Wei,Wei Du,Morihisa Fujita,Yuguang Du,Zhuo A. Wang
Chitosan and chitooligosaccharide (COS) are renowned for their potent antimicrobial prowess, yet the precise antimicrobial efficacy of COS remains elusive due to scant structural information about the utilized saccharides. This study delves into the antimicrobial potential of COS, spotlighting a distinct hetero-chitooligosaccharide dubbed DACOS. In contrast to other COS, DACOS remarkably fosters the growth of Candida tropicalis planktonic cells and fungal biofilms. Employing gradient alcohol precipitation, DACOS was fractionated, unveiling diverse structural characteristics and differential impacts on C. tropicalis . Notably, in a murine model of systemic candidiasis, DACOS, particularly its 70 % alcohol precipitates, manifests a promotive effect on Candida infection. This research unveils a new pathway for exploring the intricate nexus between the structural attributes of chitosan oligosaccharides and their physiological repercussions, underscoring the imperative of crafting chitosan and COS with meticulously defined structural configurations.
研究领域:
微生物学
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药学
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分子生物学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
·
2024
·Vol. 92
·期 1
·e13893
·
IF 2.5
Yongmei Peng,Yanan Xu,Sainan Li,Mingkun Shao,Zijia Shen,Wenjin Qi
Problem Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown. Method of Study Vaginal epithelial cells were divided into three groups: control, C. albicans strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, C. albicans (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1β and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence. Results In this study, we showed that the WT C. albicans strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells. Conclusion C. albicans activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines.
研究领域:
微生物学
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免疫学
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细胞生物学
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传染病学
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DOI
PubMed
高影响因子
Emerging Microbes & Infections
·
2024
·
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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产品关联
DOI
PubMed
高影响因子
CLINICAL ORAL IMPLANTS RESEARCH
·
2014
·Vol. 26
·期 3
·332-341
·
IF 3.123
Nicolas Villard,Chaminda Seneviratne,James Kit Hon Tsoi,Markku Heinonen,Jukka Matinlinna
Objectives The aim of the present study was to evaluate the effect of novel silane system coatings on zirconia and titanium implant surfaces and the attachment of the fungal pathogen Candida albicans . Materials and methods Titanium and zirconia specimens were silica-coated and silanized either with a commercial silane primer (RelyX Ceramic Primer™, 3M ESPE) or a novel silane system primer. The novel silane system primer was a blend of 1.0 vol% 3-acryloxypropyltrimethoxysilane and 0.3 vol% bis-1,2-(triethoxysilyl)ethane diluted in acidified ethanol-water solvent. The surface roughness (R a ), the surface free energy and the chemical composition of substrate surfaces after treatments were evaluated. C. albcans biofilms were developed on silica-coated + silanized surfaces during 48 h of incubation time. Colony forming units (CFU) and real-time PCR (RT-PCR) quantified the cells on the material surfaces. Statistical analyses were carried out by 1-way ANOVA, Tukey post hoc and Games Howell post hoc test at 5% significance level (p) . Results On zirconia and titanium surfaces, the R a and the chemical composition of the specimens were equal ( P < 0.05). The surface free energy was decreased on titanium specimens and increased on zirconia specimen after silanization. CFU of C. albicans was significantly lower on zirconia coated with RelyX Ceramic Primer™, ( P < 0.001) and on titanium coated with both silanes ( P = 0.002). RT-PCR revealed no differences between the mean quantities of C. albicans ( P ≥ 0.067). Conclusion Silica-coating and silanization had modified the titanium and zirconia surfaces significantly. Both the control and experimental silane primers might inhibit the biofilm formation of C. albicans .
研究领域:
口腔医学
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微生物学
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材料科学
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DOI
PubMed
高影响因子
Pathogens and Disease
·
2017
·Vol. 75
·期 6
·
IF 2.335
Liao Hong,Liu Shanling,Wang He,Su Hang,Liu Zhenjun
Histatin5 (Hst-5) is a member of the histatin family of antimicrobial peptides secreted by human parotid and submandibular glands. With the natural antibacterial activity, it plays an important role in the first-line barrier of oral cave against pathogens, especially for the fungal intrusion. In this study, we explored the utility of Hst-5 in the treatment of vulvovaginal candidiasis, a common condition of women of the childbearing age. We used a synthesized Hst-5 over five consecutive days as the topical treatment in a murine model of vulvovaginal candidiasis. According to the fungal colony counts, fungal burden in the vagina lavage dropped remarkably after treatment with Hst-5. Furthermore, cytological analysis of the lavage fluid indicated that the number of cast-off cells including cornified epithelial cells and inflammatory cells also decreased; histological evaluation of the vagina tissue revealed less fungi adhering to the vaginal wall in treated animals than in controls. Combined, these results suggested for the first time the potential utility of Hst-5 as a topical treatment for vulvovaginal candidiasis, uncovering the possibility of exploiting the natural antibiotic peptides in other aspects.
研究领域:
医学
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微生物学
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妇科学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Ruifang Li,Xuxia Wang,Kedong Yin,Qingpeng Xu,Shiming Ren,Xueqin Wang,Zichao Wang,Yanjie Yi
High-efficiency and low-toxic antimicrobial peptides (AMPs) are supposed to be the future candidates to solve the increasingly prominent problems of Candida albicans infection and drug resistance. Generally, introduction of hydrophobic moieties on AMPs resulted in analogues with remarkably increased activity against pathogens. CGA-N9, an antifungal peptide found in our lab, is a Candida -selective antimicrobial peptide capable of preferentially killing Candida spp. relative to benign microorganisms with low toxicities. We speculate that fatty acid modification could improve the anti- Candida activity of CGA-N9. In the present investigation, a set of CGA-N9 analogues with fatty acid conjugations at N-terminus were obtained. The biological activities of CGA-N9 analogues were determined. The results showed that the n-octanoic acid conjugation of CGA-N9 (CGA-N9-C8) was the optimal CGA-N9 analogue with the highest anti- Candida activity and biosafety; exhibited the strongest biofilm inhibition activity and biofilm eradication ability; and the highest stability against protease hydrolysis in serum. Furthermore, CGA-N9-C8 is less prone to develop resistance for C. albicans in reference with fluconazole ; CGA-N9-C8 also exhibited Candidacidal activity to the planktonic cells and the persister cells of C. albicans ; reduced C. albicans susceptibility in a systemic candidiasis mouse model. In conclusion, fatty acid modification is an effective method to enhance the antimicrobial activity of CGA-N9, and CGA-N9-C8 is a promising candidate to defend C. albicans infection and resolve C. albicans drug resistance.
研究领域:
微生物学
·
药学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Virulence
·
2024
·
IF 5.5
Fen Wang,Jinping Zhang,Qian Zhang,Zhangyong Song,Caiyan Xin
Candida albicans is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of C. albicans. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of C. albicans. In the present study, the antifungal activities of equol against C. albicans were investigated. In vitro, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against C. albicans. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of C. albicans. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors RFG1 and TUP1. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.
研究领域:
微生物学
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药理学
·
分子生物学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
BMC MICROBIOLOGY
·
2019
·Vol. 19
·期 1
·1-13
·
IF 3.287
Liao Hong,Liu Shanling,Wang He,Su Hang,Liu Zhenjun
Background Vulvovaginal candidiasis (VVC) is a common vaginitis caused by Candida species,a frequently recurring condition. Fungal azole-resistant strains with azole-resistance have developed for long and wide explosion to the first-line antifungal azole agent. Bovine lactoferrin (BLF) is a protein from transferrin family secreted by the bovine mammary tissue. Its various biological functions are well known, especially the pronounced antifungal activity. Results In the current study, we constructed a Lactobacillus casei strain ( L.casei /pPG612.1-BLF), which secreted BLF encoded by a mature secretion vector plasmid pPG612.1, and evaluated its antifungal activity in vitro and in vivo. In a two-layer agar plate in vitro assay, the number of C. albicans CFUs decreased and the average colony size shrunk upon exposure to L. casei /pPG612.1-BLF. In a murine VVC model, the infection burden of mice intra-vaginally pre-inoculated with L. casei /pPG612.1-BLF was lower than in control groups. Furthermore, the infection burden in mice with VVC was reduced when the animals were continually given L. casei /pPG612.1-BLF as a topical treatment for 5 days. Conclusion Combined, these results suggested that the L. casei /pPG612.1-BLF strain is a promising preventative and therapeutic anti-VVC agent, highlighting the possibility of employing the probiotic L. casei as a vehicle for biotherapy in the female genital tract and exploiting the natural antibiotic antimicrobial peptides for other applications.
研究领域:
微生物学
·
传染病学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·
IF 4.6
Hong Zhang,Yuanfei Zhang,Yiyang Li,Min Hu,Zihan Rong,Lingjie Meng,Xiaofei Zhang,Luan Wen,Xiumin Liang,Zhaopeng Chen,Chengcheng Liu
Vaginal candidiasis caused by Candida albicans is a chronic, recurrent disease that is difficult to treat. Current available antifungal drugs have limited efficacy and cause adverse effects necessitating novel therapeutic options. In this study, a novel metal-organic framework (MOF) containing the sonosensitizer rose bengal (RB) and decorated with silver nanoparticles (AgNPs), Fe–MOF(RB)@AgNPs (MRA), is developed which integrates chemodynamic therapy (CDT) and sonodynamic therapy (SDT) with the long-term antifungal effects of AgNPs into a single nanoscale entity. MRA exhibited low cytotoxicity in mammalian cells and strong catalytic activity for the conversion of H 2 O 2 to •OH under acidic conditions, similar to those found in vaginal candidiasis. When exposed to ultrasound, MRA generated 1 O 2 and offered rapid synergistic fungicidal effects through CDT and SDT, as well as long-lasting antifungal benefits through AgNPs, leading to the complete eradication of drug-resistant C. albicans . Moreover, MRA exhibited 99.999% efficacy against a clinical isolate of drug-resistant C. albicans at 120 µg mL −1 . Hence, MRA has considerable potential for clinical applications in the treatment of drug-resistant C. albicans -induced vaginal candidiasis.
研究领域:
材料科学
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药学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 7
·1394
·
IF 3.06
Xiaowen He,Lantong Zhang,Jinping Chen,Jinlei Sui,Guohui Yi,Jinyan Wu,Yinzheng Ma
Essential oils (EOs) have been shown to have a diversity of beneficial human health effects.Clausenais a large and highly diverse genus of plants with medicinal and cosmetic significance. The aim of this study was to analyze the composition ofClausena lansiumEOs and to investigate their potential antifungal effects. The chemical compositions ofClausena lansiumEOs obtained by hydrodistillation were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 101 compounds were identified among the diverse extracts ofC. lansium. EOs of leaves and pericarps from different cultivars (Hainan local wampee and chicken heart wampee) collected in Hainan (China) were classified into four clusters based on their compositions. These clusters showed different antifungal activities against fiveCandidaspecies (C. albicans,C. tropicalis,C. glabrata,C. kruseiandC. parapsilosis) using the disc diffusion method.Clausena lansiumEOs of pericarps displayed noteworthy antifungal activitives against all the testedCandidastrains with inhibition zone diameters in the range of 11.1–23.1 mm. EOs of leaves showed relatively low antifungal activities with inhibition zone diameters in the range of 6.5–22.2 mm. The rank order of antifungal activities among the four EO clusters was as follows: Cluster IV> Cluster III > Cluster I ≥ Cluster II. These results represent the first report about the correlation between chemical composition ofC. lansiumEOs and antifungal activity. Higher contents of β-phellandrene, β-sesquiphellandrene and β-bisabolene in EOs of pericarps were likely responsible for the high antifungal activity of Cluster IV EOs. Taken together, our results demonstrate the chemical diversity ofClausena lansiumEOs and their potential as novel antifungal agents for candidiasis caused byCandidaspp. Furthermore, the obtained results showing a wide spectrum of antifungal activities provide scientific evidence for the traditional use of these plants.Keywords:correlation;Clausena lansium;essential oil;antifungal activity;Candidaspp.
研究领域:
植物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）