The antimicrobial property of JY-1, a complex mixture of Traditional Chinese Medicine, is linked to it abilities to suppress biofilm formation and disrupt membrane permeability.

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.

Chemical composition, antifungal, and anti-virulence action of the stem bark of Hancornia speciosa Gomes (Apocynaceae) against Candida spp.

ETHNOPHARMACOLOGICAL RELEVANCE: Hancornia speciosa Gomes is a fruit and medicinal species used for treating infectious diseases of the genitourinary system. However, its mechanism of action against microbes is still not fully understood. Infections in the genitourinary system caused by Candida spp. are associated with its fungal resistance and pathogenicity. New plant-derived compounds are an alternative to fight these Candida infections. AIM OF THE STUDY: The objective of this study was to evaluate the anti-Candida effects of extracts of the stem bark of H. speciosa. This research investigated the chemical composition of sulfuric ether (EEHS) and methanolic (MEHS) extracts, their drug-modifying action on fluconazole, and their anti-virulence action on the morphological transition of Candida species. MATERIALS AND METHODS: The extracts (EEHS and MEHS) of the stem bark of H. speciosa were chemically characterized via qualitative phytochemical screening and by liquid chromatography coupled with mass spectrometry (UPLC-MS-ESI-QTOF). The extracts were evaluated regarding their antifungal effects and fluconazole-modifying activity against Candida albicans, Candida krusei, and Candida tropicalis using the broth microdilution method. Additionally, the study evaluated the inhibition of fungal virulence in Candida species through morphological transition assays. RESULTS: The phytochemical screening revealed the presence of anthocyanidins, anthocyanins, aurones, catechins, chalcones, flavones, flavonols, flavanones, leucoanthocyanidins, tannins (condensed and pyrogallic), and xanthones in both extracts of the stem bark of H. speciosa. The UPLC-MS-ESI-QTOF analysis identified the same compounds in both extracts, predominating phenolic compounds. Some compounds were first time recorded in this species: gluconic acid, cinchonain IIb, cinchonain Ib isomer, and lariciresinol hexoside isomers. Most of the intrinsic antifungal activity was observed for the MEHS against C. krusei (IC50: 58.41 µg/mL). At subinhibitory concentrations (MC/8), the EEHS enhanced the action of fluconazole against all Candida strains. The MEHS exhibited greater efficacy than fluconazole inhibiting C. krusei growth. The EEHS completely inhibited hyphae appearance and reduced pseudohyphae formation in C. albicans. CONCLUSION: The stem bark of H. speciosa is a rich source of bioactive compounds, especially phenolic. Phenolic compounds can have important roles in fighting infectious diseases of the genitourinary system, such as candidiasis. The extracts of H. speciosa improved the action of the drug fluconazole against Candida species, inhibited hyphae appearance, and reduced pseudohyphae formation. The results of this study can support the development of new therapeutics against resistant strains of Candida.

Extraradical hyphae alleviate nitrogen deposition-induced phosphorus deficiency in ectomycorrhiza-dominated forests.

The continuous imbalance between nitrogen (N) and phosphorus (P) deposition is expected to shift many ecosystems from N- to P limitation. Extraradical hyphae of ectomycorrhizal (ECM) fungi play important roles in plant nutrient acquisition under nutrient deficiency. However, whether and how ECM hyphae enhance soil P availability to alleviate N-induced P deficiency remains unclear. We investigated the impacts of ECM hyphae on transformations among different soil P fractions and underlying mechanisms under N deposition in two ECM-dominated forests. Ectomycorrhizal hyphae enhanced soil P availability under N addition by stimulating mineralization of organic P (Po) and desorption and solubilization of secondary mineral P, as indicated by N-induced increase in positive hyphal effect on plant-available P pool and negative hyphal effects on Po and secondary mineral P pools. Moreover, ECM hyphae increased soil phosphatase activity and abundance of microbial genes associated with Po mineralization and inorganic P solubilization, while decreasing concentrations of Fe/Al oxides. Our results suggest that ECM hyphae can alleviate N-induced P deficiency in ECM-dominated forests by regulating interactions between microbial and abiotic factors involved in soil P transformations. This advances our understanding of plant acclimation strategies via mediating plant-mycorrhiza interactions to sustain forest production and functional stability under changing environments.

Effect of treatment of Fusarium head blight infected barley grains with hop essential oil nanoemulsion on the quality and safety of malted barley.

Fusarium mycotoxin contamination of malting barley has been a persistent food safety issue for malting companies. In this study, the effect of hop essential oil (HEO) nanoemulsion on fungal biomass and mycotoxin production during the malting process was evaluated. Furthermore, the localization of fungal hyphae on the surface and inside the tissue of barley and malts was observed. The application of HEO nanoemulsion reduced fungal biomass and deoxynivalenol (DON) contents at each stage of the malting process as compared to control. During malting process, the fungal hyphae on kernel surfaces was reduced appreciably after steeping. However, the increment of hyphae was observed between the husk and testa layer of barley after germination than raw barley grains. In addition to its antifungal activity, the antioxidant activity of HEO in the treated malts suppressed the formation of aldehydes. This study lays the foundation for the utilization of HEO in the malting industry.

Evaluation of citrus pectin capped copper sulfide nanoparticles against Candidiasis causing Candida biofilms.

The incidence of candidiasis has significantly increased globally in recent decades, and it is a significant source of morbidity and mortality, particularly in critically ill patients. Candida sp. ability to generate biofilms is one of its primary pathogenic traits. Drug-resistant strains have led to clinical failures of traditional antifungals, necessitating the development of a more modern therapy that can inhibit biofilm formation and enhance Candida sp. sensitivity to the immune system. The present study reports the anticandidal potential of pectin-capped copper sulfide nanoparticles (pCuS NPs) against Candida albicans. The pCuS NPs inhibit C. albicans growth at a minimum inhibitory concentration (MIC) of 31.25 µM and exhibit antifungal action by compromising membrane integrity and overproducing reactive oxygen species. The pCuS NPs, at their biofilm inhibitory concentration (BIC) of 15.63 µM, effectively inhibited C. albicans cells adhering to the glass slides, confirmed by light microscopy and scanning electron microscopy. Phase contrast microscopy pictures revealed that NPs controlled the morphological transitions between the yeast and hyphal forms by limiting conditions that led to filamentation and reducing hyphal extension. In addition, C. albicans showed reduced exopolysaccharide (EPS) production and exhibited less cell surface hydrophobicity (CSH) after pCuS NPs treatment. The findings suggest that pCuS NPs may be able to inhibit the emergence of virulence traits that lead to the formation of biofilms, such as EPS, CSH, and hyphal morphogenesis. The results raise the possibility of developing NPs-based therapies for C. albicans infections associated with biofilms.

Enniatins from a marine-derived fungus Fusarium sp. inhibit biofilm formation by the pathogenic fungus Candida albicans.

Candidemia is a life-threatening disease common in immunocompromised patients, and is generally caused by the pathogenic fungus Candida albicans. C. albicans can change morphology from yeast to hyphae, forming biofilms on medical devices. Biofilm formation contributes to the virulence and drug tolerance of C. albicans, and thus compounds that suppress this morphological change and biofilm formation are effective for treating and preventing candidemia. Marine organisms produce biologically active and structurally diverse secondary metabolites that are promising lead compounds for treating numerous diseases. In this study, we explored marine-derived fungus metabolites that can inhibit morphological change and biofilm formation by C. albicans. Enniatin B (1), B1 (2), A1 (3), D (4), and E (5), visoltricin (6), ergosterol peroxide (7), 9,11-dehydroergosterol peroxide (8), and 3ß,5α,9α-trihydroxyergosta-7,22-dien-6-one (9) were isolated from the marine-derived fungus Fusarium sp. Compounds 1-5 and 8 exhibited inhibitory activity against hyphal formation by C. albicans, and compounds 1-3 and 8 inhibited biofilm formation by C. albicans. Furthermore, compounds 1-3 decreased cell surface hydrophobicity and expression of the hypha-specific gene HWP1 in C. albicans. Compound 1 was obtained in the highest yield. An in vivo evaluation system using silkworms pierced with polyurethane fibers (a medical device substrate) showed that compound 1 inhibited biofilm formation by C. albicans in vivo. These results indicate that enniatins could be lead compounds for therapeutic agents for biofilm infections by C. albicans.

Flavonoid-Rich Fractions of Bauhinia holophylla Leaves Inhibit Candida albicans Biofilm Formation and Hyphae Growth.

This study evaluated the effect of the extract and fractions of Bauhinia holophylla on Candida albicans planktonic growth, biofilm formation, mature biofilm, and hyphae growth. Three C. albicans strains (SC5314, ATCC 18804, and ATCC 10231) were tested. The crude extract and the fractions were obtained by exhaustive percolation and liquid-liquid partition, respectively. Phytochemical analyses of B. holophylla extract and fractions were performed using high-performance liquid chromatography coupled with a diode-array detector and mass spectrometry (HPLC-DAD-MS). A microdilution assay was used to evaluate the effect of the B. holophylla extract and fractions on C. albicans planktonic growth, and crystal violet staining was used to measure the total biomass of the biofilm. Hyphae growth was analyzed using light microscopy. Thirteen flavonoids were identified, with a predominance of the flavonol-3-O-glycoside type based on quercetin, myricetin, and kaempferol. Flavonoid-rich fractions of B. holophylla leaves displayed antifungal activity and inhibited both biofilm formation and hyphae growth in all the tested strains, but were not effective on C. albicans planktonic growth and mature biofilm. This study indicates that flavonoid-rich fractions from B. holophylla leaves interfere with the virulence of Candida species and support the use of Bauhinia spp. in folk medicine to treat infections.

Effects of mycorrhiza and hyphae on the response of soil microbial community to warming in eastern Tibetan Plateau.

The effects of mycorrhiza and its external hyphae on the response of soil microbes to global warming remain unclear. This study investigates the role of mycorrhiza and its hyphae in regulating soil microbial community under warming by examining the microbial biomass and composition in the ingrowth cores of arbuscular mycorrhiza (AM) plant, Fargesia nitida, and ectomycorrhiza (ECM) plant, Picea asperata, with/without mycorrhiza/hyphae and experimental warming. The results showed that warming significantly increased the biomass of all soil microbes (by 19.89%-137.48%) and altered the microbial composition in both plant plots without mycorrhiza/hyphae. However, this effect was weakened in the presence of mycorrhiza or hyphae. In F. nitida plots, warming did not significantly affect biomass and composition of most soil microbial groups when mycorrhiza or hyphae were present. In P. asperata plots, warming significantly increased the total and ECM fungi (ECMF) biomass in the presence of hyphae (p < 0.05) and the total, Gn, and AM fungi (AMF) biomass in the presence of mycorrhiza (p < 0.05). Meanwhile, the response of enzyme activities to warming was also altered with mycorrhiza or hyphae. Additionally, soil microbial community composition was mainly influenced by soil available phosphorus (avaP), while enzyme activities depended on soil avaP, dissolved organic carbon (DOC), and nitrate concentrations. Our results indicate that mycorrhiza and its hyphae are essential in regulating the response of microbes to warming.

Different susceptibility of spores and hyphae of Trichophyton rubrum to methylene blue mediated photodynamic treatment in vitro.

BACKGROUND: In recent years, methylene blue mediated-photodynamic therapy (MB-PDT) has proved to be an effective inhibitor to a variety of microorganisms, including Trichophyton rubrum, the most common dermatophyte worldwide. However, previous studies mainly focused on the spore form of T rubrum, but rarely on its hyphal form, although the latter is the main pathogenic form of T rubrum in vivo. OBJECTIVE: To investigate the inhibitory effect of MB-PDT on T rubrum in different growth phases in vitro. METHODS: The suspensions of spores and hyphae obtained from T rubrum (ATCC28188) were prepared, respectively, incubated with MB solution (0.15-40 µg/mL) and irradiated with 635 nm red light. Varied light energy and MB concentration were used. The specimen in the absence of light exposure or/and MB served as controls. MIC determination, colony counts and MTT assay were employed to evaluate the antifungal effect of MB-PDT. RESULTS: The MICs of MB-PDT for hyphae and spores of T. rubrum were 6.300 ± 1.072 µg/mL and 1.984 ± 1.072 µg/mL, respectively, at a fixed light dose of 60 J/cm2 . CFU counts gave the minimum critical combinations of MB concentration and light dose to achieve 100% inhibitory rate. For hyphae, they were 5 µg/mL + 100 J/cm2 or 10 µg/mL + 60 J/cm2 . For spores, they were 1.25 µg/mL + 40 J/cm2 or 5 µg/mL + 20 J/cm2 . The outcomes of MTT assay were consistent with those of CFU counts, but less accurate. CONCLUSION: MB-PDT is a potent inhibitor to both spores and hyphae of T. rubrum in vitro, and the spores are more sensitive to it. Its antifungal efficacy is positively correlated with the concentration of MB and light dose.

Mezoneuron benthamianum inhibits cell adherence, hyphae formation, and phospholipase production in Candida albicans.

The aim of this study was to evaluate the phytochemical constituents, antioxidant, antifungal, and anti-virulence activities of traditionally used Mezoneuron benthamianum leaves. Extracts were prepared using acetone and methanol, and the preliminary phytochemical screening was performed. The antioxidant activity was studied using the DPPH method. Anti-Candida albicans activity was established and the effect on the germ tube and phospholipase production, as well as on the host cell adherence was assessed. The extracts showed the presence of anthraquinones, cardiac glycosides, flavonoids, reducing sugars, saponins, steroids, tannins, and terpenoids. Gallic acid and trans-resveratrol were among the predominant phytochemicals found in M. benthamianum. The crude extracts presented significantly higher antioxidant activity than the ascorbic acid standard. At 0.39 mg/mL, acetone extract inhibited the growth of Candida albicans. At lower concentrations (200-50 µg/mL), it significantly inhibited the adherence ability (up to 51%), formation of hyphae (up to 65%), and the production of phospholipase. In conclusion, at high concentrations, M. benthamianum kills C. albicans, and at lower concentrations, it can inhibit the virulence properties of this pathogen. This study on crude extract validates the traditional use of this plant. However, further research is required to establish the anti-virulence activity of the two compounds and their therapeutic potential.

Accelerated corneal collagen cross-linking in clinical management of infectious keratitis.

OBJECTIVE: To evaluate the clinical efficacy of corneal collagen cross-linking (CXL) in the treatment of infectious corneal diseases. METHODS: This study retrospectively analyzed the clinical efficacy of CXL in 65 eyes with infectious keratitis in Jinan Second People's Hospital from December 2016 to June 2018. During 6 months of follow-up after CXL treatment, the results of confocal microscopy and anterior segment optical coherence tomography, as well as visual acuity and corneal biomechanical parameters, were recorded in detail. RESULTS: In general, the overall cure rate was 93.85%; no corneal endothelial dysfunction was encountered in any patients. After 6 months of follow-up, the visual acuity of cured patients was significantly enhanced, while corneal thickness was significantly reduced. Hyphae growth of patients with fungal keratitis was completely inhibited at 1 month postoperatively. Furthermore, corneal biomechanical parameters (i.e., central corneal thickness, deformation amplitude, and pachymetry intraocular pressure) were significantly improved after surgery, compared with baseline measurements. CONCLUSION: Accelerated CXL may be an effective adjuvant treatment for infectious keratitis.

The effects of clioquinol in morphogenesis, cell membrane and ion homeostasis in Candida albicans.

BACKGROUND: Candida albicans is the most prevalent opportunistic fungal pathogen. Development of antifungals with novel targets is necessary for limitations of current antifungal agents and the emergence of drug resistance. The antifungal activity of clioquinol was widely accepted while the precise mechanism was poorly understood. Hence, we aimed to seek for the possible mechanism of clioquinol against Candida albicans in the present study. RESULTS: Clioquinol could inhibit hyphae formation in a concentration-dependent manner in multiple liquid and solid media. The concentration and time-dependent anti-biofilm activities were observed in different incubation periods quantitatively and qualitatively. Further investigation found that clioquinol disrupted cell membrane directly in high concentration and induced depolarization of the membrane in low concentration. As for the influence on ion homeostasis, the antifungal effects of clioquinol could be reversed by exogenous addition of metal ions. Meanwhile, the minimum inhibitory concentration of clioquinol was increased in media supplemented with exogenous metal ions and decreased in media supplemented with exogenous metal chelators. We also found that the cellular labile ferrous iron level decreased when fungal cells were treated with clioquinol. CONCLUSION: These results indicated that clioquinol could inhibit yeast-hyphae transition and biofilm formation in Candida albicans. The effect on the cell membrane was different depending on different concentrations of clioquinol. Meanwhile, clioquinol could interfere with ion homeostasis as metal chelators for zinc, copper and iron, which was quite different with current common antifungal agents. All in all, clioquinol can be a new promising antifungal agent with novel target though more studies are needed to better understand the precise antifungal mechanism.

Inhibition of Biofilm Formation by Candida albicans and Polymicrobial Microorganisms by Nepodin via Hyphal-Growth Suppression.

Candida albicans is an opportunistic pathogenic yeast and is responsible for candidiasis. It readily colonizes host tissues and implant devices, and forms biofilms, which play an important role in pathogenesis and drug resistance. In this study, the antibiofilm, antihyphal, and antivirulence activities of nepodin, isolated from Rumex japonicus roots, were investigated against a fluconazole-resistant C. albicans strain and against polymicrobial-microorganism-biofilm formation. Nepodin effectively inhibited C. albicans biofilm formation without affecting its planktonic cell growth. Also, Rumex-root extract and nepodin both inhibited hyphal growth and cell aggregation of C. albicans. Interestingly, nepodin also showed antibiofilm activities against Candida glabrata, Candida parapsilosis, Staphylococcus aureus, and Acinetobacter baumannii strains and against dual biofilms of C. albicans and S. aureus or A. baumannii but not against Pseudomonas aeruginosa. Transcriptomic analysis performed by RNA-seq and qRT-PCR showed nepodin repressed the expression of several hypha- and biofilm-related genes (ECE1, HGT10, HWP1, and UME6) and increased the expression of several transport genes (CDR4, CDR11, and TPO2), which supported phenotypic changes. Moreover, nepodin reduced C. albicans virulence in a nematode-infection model and exhibited minimal cytotoxicity against the nematode and an animal cell line. These results demonstrate that nepodin and Rumex-root extract might be useful for controlling C. albicans infections and multispecies biofilms.

[Inhibitory effect of extract of Coptidis Rhizoma on invasion of Candida albicans hyphae in vitro].

The aim of this paper was to investigate the inhibitory effect of extract of Coptidis Rhizoma(ECR) on invasion of Candida albicans hyphae in vitro.XTT reduction method was used to evaluate the metabolic activity of C.albicans.The colony edge growth of C.albicans was observed by solid medium.The growth of C.albicans hyphae was determined on semi-solid medium.The morphology and viability changes of C.albicans hyphae were assessed by scanning electron microscope and fluorescence microscope.qRT-PCR method was used to detect the ALS3 and SSA1 expression of C.albicans invasin genes.The results showed that the metabolic viability by XTT method detected that the activity of C.albicans was gradually decreased under the intervention of 64,128 and 256 mg·L-1 of ECR respectively.128,256 mg·L-1 of ECR significantly inhibited colony folds and wrinkles on solid medium and the hyphal invasion in semi-solid medium.Scanning electron microscopy and fluorescence microscopy showed that 128,256 mg·L-1 of ECR could inhibit the formation of C.albicans hyphae.qRT-PCR results showed that the expression of invasin gene ALS3 and SSA1 was down-regulated,and especially 256 mg·L-1 of ECR could down-regulate the two genes expression by 4.8,1.68 times respectively.This study showed that ECR can affect the invasiveness of C.albicans by inhibiting the growth of hyphae and the expression of invasin.

Histone acetylation increases in response to ferulic, gallic, and sinapic acids acting synergistically in vitro to inhibit Candida albicans yeast-to-hyphae transition.

Novel treatments are needed to prevent candidiasis/candidemia infection due to the emergence of Candida species resistant to current antifungals. Considering the yeast-to-hyphae switch is a critical factor to Candida albicans virulence, phenols common in plant sources have been reported to demonstrating their ability to prevent dimorphism. Therefore, phenols present in many agricultural waste stress (ferulic (FA) and gallic (GA) acid) were initially screened in isolation for their yeast-to-hyphae inhibitory properties at times 3, 6, and 24 hr. Both FA and GA inhibited 50% of hyphae formation inhibitory concentration (IC50 ) but at a concentration of 8.0 ± 0.09 and 90.6 ± 1.05 mM, respectively, at 24 hr. However, the inhibitory effect of FA increased by 1.9-2.6 fold when combined with different GA concentrations. GA and FA values decreased even lower when sinapic acid (SA) was added as a third component. As evidenced by concave isobolograms and combination indexes less than 1, both GA:F A and GA:FA:SA combinations acted synergistically to inhibit 50% hyphae formation at 24 hr. Lastly, acetylation of histone H3 lysine 56 acetylation (H3K56) was higher in response to the triple phenolic cocktail (using the IC50 24 hr inhibitory concentration level) comparable with the nontreated samples, indicating that the phenols inhibited hyphal growth in part by targeting H3K56 acetylation.

Inhibitory effect of extract of Coptidis Rhizoma on invasion of Candida albicans hyphae in vitro / 中国中药杂志

The aim of this paper was to investigate the inhibitory effect of extract of Coptidis Rhizoma(ECR) on invasion of Candida albicans hyphae in vitro.XTT reduction method was used to evaluate the metabolic activity of C.albicans.The colony edge growth of C.albicans was observed by solid medium.The growth of C.albicans hyphae was determined on semi-solid medium.The morphology and viability changes of C.albicans hyphae were assessed by scanning electron microscope and fluorescence microscope.qRT-PCR method was used to detect the ALS3 and SSA1 expression of C.albicans invasin genes.The results showed that the metabolic viability by XTT method detected that the activity of C.albicans was gradually decreased under the intervention of 64,128 and 256 mg·L-1 of ECR respectively.128,256 mg·L-1 of ECR significantly inhibited colony folds and wrinkles on solid medium and the hyphal invasion in semi-solid medium.Scanning electron microscopy and fluorescence microscopy showed that 128,256 mg·L-1 of ECR could inhibit the formation of C.albicans hyphae.qRT-PCR results showed that the expression of invasin gene ALS3 and SSA1 was down-regulated,and especially 256 mg·L-1 of ECR could down-regulate the two genes expression by 4.8,1.68 times respectively.This study showed that ECR can affect the invasiveness of C.albicans by inhibiting the growth of hyphae and the expression of invasin.

1,4-Naphthoquinone derivatives potently suppress Candida albicans growth, inhibit formation of hyphae and show no toxicity toward zebrafish embryos.

PURPOSE: In this study, we applied various assays to find new activities of 1,4-naphthoquinone derivatives for potential anti-Candida albicans applications. METHODOLOGY: These assays determined (a) the antimicrobial effect on growth/cell multiplication in fungal cultures, (b) the effect on formation of hyphae and biofilm, (c) the influence on cell membrane integrity, (d) the effect on cell morphology using atomic force microscopy, and (e) toxicity against zebrafish embryos. We have demonstrated the activity of these compounds against different Candida species and clinical isolates of C. albicans. KEY FINDINGS: 1,4-Naphthoquinones significantly affected fungal strains at 8-250 mg l-1 of MIC. Interestingly, at concentrations below MICs, the chemicals showed effectiveness in inhibition of hyphal formation and cell aggregation in Candida. Of note, atomic force microscopy (AFM) analysis revealed an influence of the compounds on cell morphological properties. However, at low concentrations (0.8-31.2 mg l-1), it did not exert any evident toxic effects on zebrafish embryos. CONCLUSIONS: Our research has evidenced the effectiveness of 1,4-naphthoquinones as potential anti-Candida agents.

Discovery of a Novel Dibromoquinoline Compound Exhibiting Potent Antifungal and Antivirulence Activity That Targets Metal Ion Homeostasis.

Globally, invasive fungal infections pose a significant challenge to modern human medicine due to the limited number of antifungal drugs and the rise in resistance to current antifungal agents. A vast majority of invasive fungal infections are caused by species of Candida, Cryptococcus, and Aspergillus. Novel antifungal molecules consisting of unexploited chemical scaffolds with a unique mechanism are a pressing need. The present study identifies a dibromoquinoline compound (4b) with broad-spectrum antifungal activity that inhibits the growth of pertinent species of Candida (chiefly C. albicans), Cryptococcus, and Aspergillus at a concentration of as low as 0.5 µg/mL. Furthermore, 4b, at a subinhibitory concentration, interfered with the expression of two key virulence factors (hyphae and biofilm formation) involved in C. albicans pathogenesis. Three yeast deletion strains ( cox17Δ, ssa1Δ, and aft2Δ) related to metal ion homeostasis were found to be highly sensitive to 4b in growth assays, indicating that the compound exerts its antifungal effect through a unique, previously unexploited mechanism. Supplementing the media with either copper or iron ions reversed the strain sensitivity to 4b, further corroborating that the compound targets metal ion homeostasis. 4b's potent antifungal activity was validated in vivo, as the compound enhanced the survival of Caenorhabditis elegans infected with fluconazole-resistant C. albicans. The present study indicates that 4b warrants further investigation as a novel antifungal agent.

Fungus hyphae-supported alumina: An efficient and reclaimable adsorbent for fluoride removal from water.

A reclaimable adsorbent of fungus hyphae-supported alumina (FHSA) bio-nanocomposites was developed, characterized and applied in fluoride removal from water. This adsorbent can be fast assembled and disassemble reversibly, promising efficient reclamation and high accessible surface area for fluoride adsorption. Adsorption experiments demonstrate that the FHSA performed well over a considerable wide pH range of 3-10 with high fluoride removal efficiencies (>66.3%). The adsorption capacity was 105.60mgg-1 for FHSA, much higher than that for the alumina nanoparticles (50.55mgg-1) and pure fungus hyphae (22.47mgg-1). The adsorption capacity calculated by the pure content of alumina in the FHSA is 340.27mgg-1 of alumina. Kinetics data reveal that the fluoride adsorption process on the FHSA was fast, nearly 90% fluoride adsorption can be achieved within 40min. The fluoride adsorption on the FHSA is mainly due to the surface complexes formation of fluoride with AlOH and the attraction between protonated NH2 and fluoride through hydrogen bonding. Findings demonstrate that the FHSA has potential applicability in fluoride removal due to its strong fluoride adsorbility and the easy reclamation by its fast reversible assembly and disassembly feature.

Efficient dibutyltin (DBT) elimination by the microscopic fungus Metarhizium robertsii under conditions of intensive aeration and ascorbic acid supplementation.

Dibutyltin (DBT) is an environmental pollutant characterized by immunotoxic, neurotoxic, and pro-oxidant properties. In this study, an attempt was made to enhance DBT elimination by the Metarhizium robertsii strain. We observed enhanced fungal growth in the bioreactor (pO2 ≥ 20%) compared to flask cultures (µ max increased from 0.061 to 0.086 h-1). Moreover, under aerated conditions, M. robertsii mycelium with "hairy" morphology biodegraded DBT (20 mg l-1) 10-fold faster in the bioreactor than in the flask cultures. Monobutyltin (MBT) and a hydroxylated derivative of MBT (OHBuSnH2) were detected as by-products of dibutyltin debutylation. Simultaneous usage of glucose and butyltins indicates the comatabolic nature of monobutyltin and dibutyltin removal. In order to protect fungal cells from oxidative stress caused by DBT presence, vitamin C (20 mg l-1) was applied. Supplementation with ascorbic acid (AA) resulted in a 3-fold acceleration of MBT removal during the first 7 h of incubation. Using the HPLC-MS/MS technique, a quantitative analysis of malondialdehyde (MDA), a marker of oxidative stress, was performed. In the AA presence, a decrease in the MDA amount (about 45%) was observed compared to the case with fungal cells exposed to DBT alone.