Induction of Defense Gene Expression and the Resistance of Date Palm to Fusarium oxysporum f. sp. Albedinis in Response to Alginate Extracted from Bifurcaria bifurcata.

In many African countries, the Bayoud is a common disease spread involving the fungus Fusarium oxusporum f. sp. albedinis (Foa). The induction of plant natural defenses through the use of seaweed polysaccharides to help plants against pathogens is currently a biological and ecological approach that is gaining more and more importance. In the present study, we used alginate, a natural polysaccharide extracted from a brown algae Bifurcaria bifurcata, to activate date palm defenses, which involve phenylalanine ammonia-lyase (PAL), a key enzyme of phenylpropanoid metabolism. The results obtained showed that at low concentration (1 g·L-1), alginate stimulated PAL activity in date palm roots 5 times more compared to the negative control (water-treated) after 24 h following treatment and 2.5 times more compared to the laminarin used as a positive stimulator of plant natural defenses (positive control of induction). Using qRT-PCR, the expression of a selection of genes involved in three different levels of defense mechanisms known to be involved in response to biotic stresses were investigated. The results showed that, generally, the PAL gene tested and the genes encoding enzymes involved in early oxidative events (SOD and LOX) were overexpressed in the alginate-treated plants compared to their levels in the positive and negative controls. POD and PR protein genes selected encoding ß-(1,3)-glucanases and chitinases in this study did not show any significant difference between treatments; suggesting that other genes encoding POD and PR proteins that were not selected may be involved. After 17 weeks following the inoculation of the plants with the pathogen Foa, treatment with alginate reduced the mortality rate by up to 80% compared to the rate in control plants (non-elicited) and plants pretreated with laminarin, which agrees with the induction of defense gene expression and the stimulation of natural defenses in date palm with alginate after 24 h. These results open promising prospects for the use of alginate in agriculture as an inducer that triggers immunity of plants against telluric pathogens in general and of date palm against Fusarium oxysporum f. sp. albedinis in particular.

Inhibiting miR-129-5p alleviates inflammation and modulates autophagy by targeting ATG14 in fungal keratitis.

To investigate the role of miR-129-5p in inflammation and autophagy in fungal keratitis, we established a keratitis mouse model infected with Fusarium solani (F. solani) and conducted experiments on corneal stromal cells infected with F. solani. The expression of miR-129-5p was detected via quantitative real-time polymerase chain reaction (PCR). The miR-129-5p antagomir was used to transfect cells and mice to study the regulatory role of miR-129-5p in autophagy and inflammation after fungal infection. The expression of Beclin1 and LC3B and colocalization of LC3B with lysosomes were detected via Western blotting and immunofluorescence. CCK-8 was used to determine the viability of corneal stromal cells. The expression of IL-1ß were detected by ELISA. Bioinformatics software was used to predict the potential targets of miR-129-5p, which were verified by a luciferase reporter gene assay. RT-PCR showed that miR-129-5p expression in mouse corneas was significantly increased after infection with F. solani. Subconjunctival injection of the miR-129-5p antagomir significantly enhanced the proteins Beclin-1 and LC3B. At the same time, inhibiting miR-129-5p expression could reduce the inflammatory response in FK and significantly increase the viability of corneal stromal cells infected with F. solan. Moreover, the dual luciferase reporter assay indicated that Atg14 was a direct target of miR-129-5p. Our study shows that miR-129-5p is a novel small molecule that regulates autophagy by targeting Atg14, indicating that it may be a proinflammatory and therapeutic target for fungal keratitis.

Inhibition of miR-665-3p Enhances Autophagy and Alleviates Inflammation in Fusarium solani-Induced Keratitis.

Purpose: Accumulated evidence has shown that microRNAs (miRNAs) are closely related with the regulation of autophagy, which plays vital roles in fungal keratitis (FK). Microarray data showed elevated expression of miR-665-3p in mouse corneal tissues after infection with Fusarium solani (F. solani). Here, we investigated the effect of miR-665-3p in regulating autophagy in experimental F. solani keratitis and determined the potential molecular mechanisms involved. Methods: In this article, we established an in vivo mouse model of FK and an in vitro model of corneal stromal cells by inoculating with F. solani. We divided them into the following six groups: control, chloroquine (CQ), rapamycin (Rapa), miR-665-3p antagomir (ant-665), miR-665-3p agomir (miR-665), and the negative control group (miR-NC). The levels of autophagy were detected by electron microscopy, Western blotting, and immunofluorescence. Then, we used a dual-luciferase reporter assay to determine the binding of miR-665-3p to the autophagy-related gene (ATG)5 3'UTR. Detection of IL-1ß protein levels and hematoxylin and eosin (H&E) staining of corneal tissues were used to observe the effect of miR-665-3p on inflammation in FK. Results: Here, we showed that inhibition of miR-665-3p expression in FK upregulated autophagy and alleviated inflammation. Nevertheless, the opposite results were found by overexpressing miR-665-3p. Additionally, ATG5 was a direct target gene for miR-665-3p. Conclusions: Together, our data demonstrated that miR-665-3p might be involved in F. solani keratitis of mice by regulating autophagic pathways and inflammation.

Fusarium infections: Epidemiological aspects over 10 years in a university hospital in France.

BACKGROUND: Fusarium is an environmental mold that causes deep or superficial mycosis in immunocompromised or immunocompetent patients respectively. METHODS: This epidemiological study evaluated the frequency of Fusarium infections in our university hospital center in France over a decade from 2007 to 2016 and its representativeness in the main clinical infections. RESULTS: A total of 715 Fusarium sp. were isolated from various sampling sites. Fusarium was detected in 0.47% of blood cultures, 31.1% of ophthalmic samples, and 8.48% of nail samples. The frequency of Fusarium infections was stable over this decade. CONCLUSIONS: The main Fusarium species complexes recorded in this study were Fusarium oxysporum species complex and Fusarium solani species complex, indicating the importance of Fusarium as a fungal agent that should be considered in clinical practice. A focus on invasive fusarioses shows that they all occur in hematology patients.

Seed biopriming with antagonistic microbes and ascorbic acid induce resistance in tomato against Fusarium wilt.

Seed biopriming is an emerging technique to enhance seed germination under stress conditions. An integrated approach of tomato seed biopriming with ascorbic acid, Trichoderma asperellum BHU P-1 and Ochrobactrum sp. BHU PB-1 was applied to observe the response against wilt pathogen of tomato Fusarium oxysporum f. sp. lycopersici (FOL). Tomato seeds bioprimed with the aforementioned application expressed augmented seed germination and activated of defense response. Seed germination was recorded higher (80 %) at low concentration (1 pM) of ascorbic acid as compared to high concentration of 1 mM (41 %). Combination of both ascorbic acid and antagonistic microbe treatments (T5 & T6) significantly reduced disease incidence (up to 28 %) in tomato plants at 10 days. T5 and T6 treated plants exhibited higher accumulation of total phenol content and increased activity of Phenylammonia lyase (PAL), Peroxidase (PO), Chitinase (Chi) and Polyphenol oxidase (PPO) as compared to control (T1) plants. ROS formation in the form of H2O2 was also found to be reduced in combined treatment. Histochemical analysis revealed that phenylpropanoid pathway (lignin deposition) was more activated in combined priming treatment plants as compared to individual treatment upon challenge inoculation with FOL. Transcript expression analysis of defense genes confirmed the up-regulation of PAL (2.1 fold), Chi (0.92 fold), Pathogenesis related proteins (PR) (1.58 fold) and Lipoxygenase (Lox) (0.72 fold) in T6 treatment as compared to T1 treatment plants at 96 h. This study reveals that ascorbic acid treatment with antagonistic microbes through seed priming effectively induced seed germination and elicited defense mechanism to control wilt disease in tomato plants.

Risk of invasive fungal infections in patients with high-risk MDS and AML receiving hypomethylating agents.

Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre-specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold-active prophylaxis can be considered in patients who are neutropenic at the start of therapy.

A phosphorylated transcription factor regulates sterol biosynthesis in Fusarium graminearum.

Sterol biosynthesis is controlled by transcription factor SREBP in many eukaryotes. Here, we show that SREBP orthologs are not involved in the regulation of sterol biosynthesis in Fusarium graminearum, a fungal pathogen of cereal crops worldwide. Instead, sterol production is controlled in this organism by a different transcription factor, FgSR, that forms a homodimer and binds to a 16-bp cis-element of its target gene promoters containing two conserved CGAA repeat sequences. FgSR is phosphorylated by the MAP kinase FgHog1, and the phosphorylated FgSR interacts with the chromatin remodeling complex SWI/SNF at the target genes, leading to enhanced transcription. Interestingly, FgSR orthologs exist only in Sordariomycetes and Leotiomycetes fungi. Additionally, FgSR controls virulence mainly via modulating deoxynivalenol biosynthesis and responses to phytoalexin.

Outcomes of patients with invasive fusariosis who undergo further immunosuppressive treatments, is there a role for secondary prophylaxis?

BACKGROUND: Patients treated for invasive aspergillosis may relapse during subsequent periods of immunosuppression and should receive secondary prophylaxis. Little is known about the frequency of relapse and practices of secondary prophylaxis for invasive fusariosis (IF). OBJECTIVES: Evaluate practices of secondary prophylaxis and the frequency of relapse in patients who survived IF and were exposed to subsequent periods of immunosuppression. METHODS: Multicentre retrospective study of patients with haematological malignancies who developed IF, survived the initial fungal disease period, and were exposed to subsequent periods of immunosuppression. RESULTS: Among 40 patients, 35 received additional chemotherapy and developed neutropenia (median, 24 days; range, 4-104), and five received glucocorticoids for the treatment of graft-vs-host disease. Overall, 32 patients received secondary prophylaxis (voriconazole in 24) for a median of 112 days (range, 12-468). IF relapsed in five patients (12.5%): 2/8 (25%) not on prophylaxis and 3/32 (9.4%) receiving prophylaxis. Among 28 patients with disseminated IF, relapse occurred in 2/2 (100%) not on prophylaxis and in 3/26 (11.5%) on prophylaxis (P = 0.03). All patients who relapsed IF died. CONCLUSIONS: Patients with IF who survive the initial disease may relapse if exposed to subsequent episodes of immunosuppressive therapies. Secondary prophylaxis should be considered, especially if IF was disseminated.

Control of Fusarium wilt of lisianthus by reassembling the microbial community in infested soil through reductive soil disinfestation.

Continuous monocropping often influences negatively the soil microbial community and leads to the occurrence of soil-borne diseases. In this study, a pre-cultivation soil management strategy, reductive soil disinfestation (RSD), involving amendment by the use of reed straw, bagasse, and rice straw, and creating anaerobic soil conditions, was used to regulate the microbial community in a soil infested by Fusarium wilt of lisianthus and make it suitable for plant cultivation. The results showed that RSD significantly decreased F. oxysporum population by 97.1%-99.1% and the incidence of lisianthus wilt disease to 3.0%-14.3% compared with that of the untreated soil. The lowest disease incidence was found in the soil treated with RSD where bagasse was incorporated. The replantation of the host plant differently stimulated the pathogen proliferations across the different soils. MiSeq sequencing and culture-dependent investigation showed that the RSD treatments established distinct microbial communities compared to that of the untreated soil. Furthermore, the relative abundances of representatives of the families Cytophagaceae, Chitinophagaceae, Chaetomiaceae, and an unclassified family within Sordariomycetes, as well as soil microbial activity and the proportions of antagonists were significantly and negatively correlated with the pathogen population increase. Overall, the RSD treatment contributed to the reassembly of the soil microbiome which contained more beneficial agents that successfully controlled the pathogen inoculum level and lisianthus Fusarium wilt disease.

Efficacy of Amphotericin B Against Fusarium and Aspergillus in Corneal Storage Medium.

PURPOSE: The incidence of postkeratoplasty fungal infection is increasing in the United States, and our most commonly used corneal storage medium, Optisol-GS, contains antibiotics but no antifungal agents. We previously demonstrated the efficacy of amphotericin B additives in eliminating Candida albicans contaminants in Optisol-GS. The purpose of this study was to determine whether amphotericin B would also be efficacious against Fusarium solani and Aspergillus fumigatus. METHODS: Vials of Optisol-GS were supplemented with 0.255 µg/mL of amphotericin B. Half of the vials were inoculated with F. solani and half with A. fumigatus. Positive control vials were inoculated with the fungi but no amphotericin B. The vials were refrigerated, sampled, and plated at different time points. The plates were then incubated at 36°C for 48 hr after which fungal colony counts were performed. RESULTS: There was an average reduction in the growth of F. solani in the amphotericin B-supplemented vials of 44% on day 2, 79% on day 7, and 80% on day 14 when compared with the positive control vials. There was an average reduction in the growth of A. fumigatus in the amphotericin B-supplemented vials of 40% on day 2 and 14% on day 7 when compared with the positive control vials. Both amphotericin B-supplemented and control vials grew less than 2 colonies of A. fumigatus on day 14. CONCLUSIONS: This study suggests that amphotericin B additives in Optisol-GS reduce the growth of F. solani and A. fumigatus.

Disseminated fusariosis with cutaneous involvement in hematologic malignancies: report of six cases with high mortality rate

Abstract: Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

Disseminated fusariosis with cutaneous involvement in hematologic malignancies: report of six cases with high mortality rate.

Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

Effect of Silver Nanoparticles on Toxigenic Fusarium spp. and Deoxynivalenol Secretion in Some Grains.

BACKGROUND: Deoxynivalenol (DON) is one of the most important fungal mycotoxins excreted by different Fusarium species in many types of grains and food commodities. It has high damage impact on human and animal immune systems. OBJECTIVE: This in vitro study aimed to evaluate the influence of silver nanoparticles (Ag-NPs) as an inhibitor for the DON toxin excreted from some Fusarium spp., which were isolated from barely, wheat, and corn grains. METHODS: Ag-NPs were estimated on Minimum Inhibitory Concentration, using levels of 5, 25, 50, 75, and 100 ppm, while the effect on DON was conducted with ELISA. Tri13 and Tri7 primers were used to evaluate the impact of Ag-NPs on the DNA of tested toxigenic Fusarium isolates. RESULTS: Results revealed that the relative density values (Rd, %) of the isolated Fusarium from barley, wheat, and corn grains were 41.27, 26.47, and 30.76%, respectively. The predominant fungus was F. graminearum and F. culmorum in wheat and barley, respectively. The maximum inhibition diameters used for concentrations were 0.5, 2.8, 3.2, 3.3, and 3.31 mm, respectively. The impact of Ag-NPs on genomic structure was limited. Results demonstrated that Ag-NPs have the ability to reduce the linear growth of Fusarium spp. and eliminate the DON toxin to 34.44, 34.60, and 34.89% at 50, 75, and 100 ppm. CONCLUSIONS: Ag-NPs are considered nontransgenic substances, and their impact on Fusarium DNA under tested concentrations has been neglected. Ag-NPs may work as an alternative to fungicides to reduce fungal growth and eliminate DON mycotoxins.

Inhibition of Fusarium solani Infection in Murine Keratocytes by Lactobacillus salivarius ssp. salivarius JCM1231 Culture Filtrate In Vitro.

PURPOSE: To explore the inhibitory activity of Lactobacillus salivarius ssp. salivarius JCM1231 (L. salivarius JCM1231) culture filtrate against Fusarium solani (F. solani) and its effects on murine keratocytes (MKs) infected with F. solani. METHODS: L. salivarius JCM1231 was cultured in an anaerobic incubator for 24 h, and the L. salivarius culture filtrate (LSCF) was prepared .The antifungal activity of L. salivarius JCM1231 against F. solani was determined with a plate overlay assay, agar diffusion assay, and conidial germination inhibition test. The effects of temperature, pH, and proteolytic enzymes on the antifungal activity of LSCF were detected with microtiter plate-well assay and conidial germination inhibition assay. Furthermore, the effects of LSCF on MKs infected with F. solani were detected. Cell activity and apoptosis were measured using methylthiazoletetrazolium assays and flow cytometry analysis, respectively. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) cytokines were measured using real-time polymerase chain reactions and enzyme-linked immunosorbent assays (ELISA), and mycotoxin production was detected with high-performance liquid chromatography tandem mass spectrometry. RESULTS: Conidial germination and mycelia growth of F. solani were significantly inhibited by LSCF. The antifungal substances produced by L. salivarius JCM1231 were heat unstable, proteinaceous, and sensitive to proteolytic enzymes and were active within a narrow acidic pH range between 2.0 and 4.0. In the presence of 15 µg/ml of LSCF, cell activity was significantly increased, and cell apoptosis, the level of IL-6 and TNF-α expressions, and mycotoxin (zearalenone and fumonisin B1) productions were decreased significantly in MKs infected with F. solani. CONCLUSION: L. salivarius JCM1231 culture filtrate can effectively inhibit F. solani growth and protect MKs against F. solani infection.

First report of Fusarium oxysporum species complex infection in zebrafish culturing system.

Fusarium oxysporum species complex (FOSC) is a highly diverse fungus. Recently, F. oxysporum infection was identified from zebrafish (Danio rerio) culturing system in Korea. Initially, a rapid whitish smudge was appeared in the water with the fungal blooming on walls of fish tanks. Microscopic studies were conducted on fungal hyphae, colony pigmentation and chlamydospore formation and the presence of macro- and microspores confirmed that the isolated fungus as F. oxysporum. Furthermore, isolated F. oxysporum was confirmed by internal transcribed spacer sequencing which matched (100%) to nine F. oxysporum sequences available in GenBank. Experimental hypodermic injection of F. oxysporum into adult zebrafish showed the development of fungal mycelium and pathogenicity similar to signs observed. Histopathologic results revealed a presence of F. oxysporum hyphae in zebrafish muscle. Fusarium oxysporum growth was increased with sea salt in a concentration-dependent manner. Antifungal susceptibility results revealed that F. oxysporum is resistant to copper sulphate (up to 200 µg mL-1 ) and sensitive to nystatin (up to 40 µg mL-1 ). This is the first report of FOSC from zebrafish culture system, suggesting it appears as an emerging pathogen, thus posing a significant risk on zebrafish facilities in the world.

Effects of iron and boron combinations on the suppression of Fusarium wilt in banana.

The effects of mineral nutrient on banana wilt disease, which are the result of a competitive relationship between host plants and pathogens, can affect the interactions of plants with microorganisms. To investigate the mineral nutrient effect, hydroponic experiments were conducted in glasshouse containing combinations of low, medium, and high iron (Fe) and boron (B) concentrations, followed by pathogen inoculation. High Fe and B treatment significantly reduced the disease index and facilitated plants growth. With increasing Fe and B concentrations, more Fe and B accumulated in plants. High Fe and B treatment dramatically reduced the Fusarium oxysporum conidial germination rate and fungal growth compared with the other two treatments, contributing to decreased numbers of the pathogen on infected plants. Furthermore, High Fe and B treatment decreased the fusaric acid production of F. oxysporum in vitro and also increased the mannitol content of the plants, which in turn decreased the phytotoxin production of infected plants and finally reduced the disease index due to the virulence factor of phytotoxin. Taken together, these results indicate that Fe and B play a multifunctional role in reducing the severity of diseases by affecting the growth of F. oxysporum and the responses between plants and pathogens.

An RNAi-Based Control of Fusarium graminearum Infections Through Spraying of Long dsRNAs Involves a Plant Passage and Is Controlled by the Fungal Silencing Machinery.

Meeting the increasing food and energy demands of a growing population will require the development of ground-breaking strategies that promote sustainable plant production. Host-induced gene silencing has shown great potential for controlling pest and diseases in crop plants. However, while delivery of inhibitory noncoding double-stranded (ds)RNA by transgenic expression is a promising concept, it requires the generation of transgenic crop plants which may cause substantial delay for application strategies depending on the transformability and genetic stability of the crop plant species. Using the agronomically important barley-Fusarium graminearum pathosystem, we alternatively demonstrate that a spray application of a long noncoding dsRNA (791 nt CYP3-dsRNA), which targets the three fungal cytochrome P450 lanosterol C-14α-demethylases, required for biosynthesis of fungal ergosterol, inhibits fungal growth in the directly sprayed (local) as well as the non-sprayed (distal) parts of detached leaves. Unexpectedly, efficient spray-induced control of fungal infections in the distal tissue involved passage of CYP3-dsRNA via the plant vascular system and processing into small interfering (si)RNAs by fungal DICER-LIKE 1 (FgDCL-1) after uptake by the pathogen. We discuss important consequences of this new finding on future RNA-based disease control strategies. Given the ease of design, high specificity, and applicability to diverse pathogens, the use of target-specific dsRNA as an anti-fungal agent offers unprecedented potential as a new plant protection strategy.

Antimold Prophylaxis May Reduce the Risk of Invasive Fusariosis in Hematologic Patients with Superficial Skin Lesions with Positive Culture for Fusarium.

Hematologic patients with superficial skin lesions on admission growing Fusarium spp. are at a high risk for developing invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing invasive fusariosis in these patients. Between August 2008 and December 2014, patients with acute leukemia or aplastic anemia and recipients of hematopoietic cell transplants were screened on admission with dermatologic and direct exams and fungal cultures of superficial skin lesions. Until November 2009, no interventions were made. Beginning in December 2009, patients with baseline skin lesions and a direct exam and/or culture suggestive of the presence of Fusarium spp. received prophylaxis with voriconazole or posaconazole. Skin lesions in the extremities (mostly onychomycosis and interdigital intertrigo) were present on admission in 88 of 239 episodes (36.8%); 44 lesions had hyaline septate hyphae identified by direct exam, and cultures from 11 lesions grew Fusarium spp. Antimold prophylaxis was given for 20 episodes (voriconazole for 17 and posaconazole for 3). Invasive fusariosis was diagnosed in 14 episodes (5.8%). Among patients with baseline skin lesions with positive cultures for Fusarium spp., 4 of 5 without antimold prophylaxis developed invasive fusariosis versus 0 of 6 with antimold prophylaxis (P = 0.01; 95% confidence interval for the difference between proportions, 22% to 96%). Primary antifungal prophylaxis with an antimold azole may prevent the occurrence of invasive fusariosis in high-risk hematologic patients with superficial skin lesions on admission growing Fusarium spp.

Inhibitory mechanism of butylated hydroxyanisole against infection of Fusarium proliferatum based on comparative proteomic analysis.

UNLABELLED: Fusarium proliferatum as a filamentous fungal pathogen can produce mycotoxins that can contaminate postharvest fruits and thus impact risks on human health. The extracellular proteomes of F. proliferatum grown in the absence and presence of butylated hydroxyanisole (BHA) were analyzed comparatively. A total of 66 significantly different expressed secreted proteins were identified by LC-ESI-MS/MS analysis. The BHA treatment suppressed the accumulation of some pathogenic factors such as aspartic protease, cell wall degradation enzymes, porin, superoxide dismutase and glyceraldehyde-3-phosphate dehydrogenase. On the contrary, the BHA treatment increased the abundances of some proteins, such as ATP binding cassette transporter substrate-binding protein and lipopolysaccharide-assembly lipoprotein, involved in the growth of F. proliferatum. These findings suggest that BHA treatment could influence the pathogenic ability of F. proliferatum via inhibiting the levels of virulence factors and cell wall degradation-associated enzymes. Moreover, the induction of the growth-related proteins after the BHA treatment suggests that the livelihood of F. proliferatum might depend on the cost of reduced pathogenic ability. This study has provided some evidence for understanding the complicated mechanisms of F. proliferatum infection in an effort to develop new targets for the control of this fungal pathogen. BIOLOGICAL SIGNIFICANCE: To better understand the inhibitory mechanism of F. proliferatum by butylated hydroxyanisole (BHA) treatment, a comprehensive proteomic analysis of the secreted proteins of F. proliferatum was firstly conducted. Among the 66 identified spots, 34 and 32 proteins were down- and up-accumulated significantly by BHA treatment, respectively. Many of the identified key protein species were involved in the pathogenic ability and the growth of F. proliferatum. This study is helpful for broadening our knowledge of the pathogenic mechanism of F. proliferatum.