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Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora , with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium , and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium , as it remains the best scientific, nomenclatural, and practical taxonomic option available.

Cu is an essential trace element for cell growth and proliferation. However, excess of Cu accumulation leads to cellular toxicity. Thus, precise and tight regulation of Cu homeostasis processes, including transport, delivery, storage, detoxification, and efflux machineries, is required. Moreover, the maintenance of Cu homeostasis is critical for the survival and virulence of fungal pathogens. Cu homeostasis has been extensively studied in mammals, bacteria, and yeast, but it has not yet been well documented in filamentous fungi. In the present work, we investigated Cu tolerance in the filamentous fungus Fusarium oxysporum by analysing the Cu transporter coding gene crpF , previously studied in Aspergillus fumigatus . The expression studies demonstrated that crpF is upregulated in the presence of Cu and its deletion leads to severe sensitivity to low levels of CuSO 4 in F. oxysporum . Targeted deletion of crpF did not significantly alter the resistance of the fungus to macrophage killing, nor its pathogenic behaviour on the tomato plants. However, the targeted deletion mutant Δ crpF showed increased virulence in a murine model of systemic infection compared to wild-type strain (wt).

This article is to alert medical mycologists and infectious disease specialists of recent name changes of medically important species of the filamentous mold Fusarium Fusarium species can cause localized and life-threating infections in humans. Of the 70 Fusarium species that have been reported to cause infections, close to one-third are members of the Fusarium solani species complex (FSSC), and they collectively account for approximately two-thirds of all reported Fusarium infections. Many of these species were recently given scientific names for the first time by a research group in the Netherlands, but they were misplaced in the genus Neocosmospora In this paper, we present genetic arguments that strongly support inclusion of the FSSC in Fusarium There are potentially serious consequences associated with using the name Neocosmospora for Fusarium species because clinicians need to be aware that fusaria are broadly resistant to the spectrum of antifungals that are currently available.

Soil organisms exhibit high tolerance to heavy metals, probably acquired through evolutionary adaptation to contaminated environments. Essentially, metal tolerance in fungi involves several specific and non-specific mechanisms that include metal efflux, metal binding to cell walls, extracellular and intracellular sequestration and complexation with proteins. However, fungi have adopted different strategies to detoxify heavy metals, although species differ in the mechanisms used. In this complex molecular framework, metallothioneins (MTs) are becoming increasingly relevant in metal homeostasis, even though little is known about their role in metal adaptation and virulence in fungal pathogens. With the aim to decipher the function of metallothioneins in the opportunistic fungus Fusarium oxysporum, we have carried out an in silico analysis that revealed the presence of a hypothetical metallothionein (mt1) that has multiple metal responsive elements in its promoter region and conserved cysteine motifs in its coding sequence. Characterization of strain Δmt1 deficient in the mt1 gene revealed higher sensitivity of this mutant to copper, cadmium and zinc compared to the wild type strain (wt). Expression analyses revealed that Zn specifically activates mt1, but the lack of this gene did not lead to a transcriptional up-regulation of genes gapdh and prx, associated with the oxidative stress response. The lack of mt1 did not alter the pathogenic capacity of the fungus, either in tomato plant or in a murine model of systemic infection. Nevertheless, Δmt1 displayed lower resistance to macrophage killing, suggesting a connection between the absence of mt1 and impaired defence capacity against copper and reactive oxygen species.

The efficacy of liposomal amphotericin B and voriconazole was evaluated against the systemic infection by Fusarium oxysporum species complex or Fusarium keratoplasticum. Although MIC values were within the epidemiological cutoff values (ECVs) recently stablished for Fusarium spp., no efficacy was obtained, indicating that ECVs for Fusarium are not relevant for in vivo efficacy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fusariosis have been increasing in Colombia in recent years, but its epidemiology is poorly known. We have morphologically and molecularly characterized 89 isolates of Fusarium obtained between 2010 and 2012 in the cities of Bogotá and Medellín. Using a multi-locus sequence analysis of rDNA internal transcribed spacer, a fragment of the translation elongation factor 1-alpha (Tef-1α) and of the RNA-dependent polymerase subunit II (Rpb2) genes, we identified the phylogenetic species and circulating haplotypes. Since most of the isolates studied were from onychomycoses (nearly 90 %), we carried out an epidemiological study to determine the risk factors associated with such infections. Five phylogenetic species of the Fusarium solani species complex (FSSC), i.e., F. falciforme, F. keratoplasticum, F. lichenicola, F. petroliphilum, and FSSC 6 as well as two of the Fusarium oxysporum species complex (FOSC), i.e., FOSC 3 and FOSC 4, were identified. The most prevalent species were FOSC 3 (38.2%) followed by F. keratoplasticum (33.7%). In addition, our isolates were distributed into 23 haplotypes (14 into FOSC and nine into FSSC). Two of the FSSC phylogenetic species and two haplotypes of FSSC were not described before. Our results demonstrate that recipients of pedicure treatments have a lower probability of acquiring onychomycosis than those not receiving such treatments. The antifungal susceptibility of all the isolates to five clinically available agents showed that amphotericin B was the most active drug, while the azoles exhibited lower in vitro activity.

Fungal pathogens provoke devastating losses in agricultural production, contaminate food with mycotoxins and give rise to life-threatening infections in humans. The soil-borne ascomycete Fusarium oxysporum attacks over 100 different crops and can cause systemic fusariosis in immunocompromised individuals. Here we functionally characterized VeA, VelB, VelC and LaeA, four components of the velvet protein complex which regulates fungal development and secondary metabolism. Deletion of veA, velB and to a minor extent velC caused a derepression of conidiation as well as alterations in the shape and size of microconidia. VeA and LaeA were required for full virulence of F. oxysporum on tomato plants and on immunodepressed mice. A critical contribution of velvet consists in promoting chromatin accessibility and expression of the biosynthetic gene cluster for beauvericin, a depsipeptide mycotoxin that functions as a virulence determinant. These results reveal a conserved role of the velvet complex during fungal infection on plants and mammals., (© 2012 Blackwell Publishing Ltd.)

Soilborne fungal pathogens cause devastating yield losses and are highly persistent and difficult to control. During the infection process, these organisms must cope with limited availability of iron. Here we show that the bZIP protein HapX functions as a key regulator of iron homeostasis and virulence in the vascular wilt fungus Fusarium oxysporum. Deletion of hapX does not affect iron uptake but causes derepression of genes involved in iron-consuming pathways, leading to impaired growth under iron-depleted conditions. F. oxysporum strains lacking HapX are reduced in their capacity to invade and kill tomato (Solanum lycopersicum) plants and immunodepressed mice. The virulence defect of ΔhapX on tomato plants is exacerbated by coinoculation of roots with a biocontrol strain of Pseudomonas putida, but not with a siderophore-deficient mutant, indicating that HapX contributes to iron competition of F. oxysporum in the tomato rhizosphere. These results establish a conserved role for HapX-mediated iron homeostasis in fungal infection of plants and mammals.

The pathogenesis-related PR-1-like protein family comprises secreted proteins from the animal, plant, and fungal kingdoms whose biological function remains poorly understood. Here we have characterized a PR-1-like protein, Fpr1, from Fusarium oxysporum, an ubiquitous fungal pathogen that causes vascular wilt disease on a wide range of plant species and can produce life-threatening infections in immunocompromised humans. Fpr1 is secreted and proteolytically processed by the fungus. The fpr1 gene is required for virulence in a disseminated immunodepressed mouse model, and its function depends on the integrity of the proposed active site of PR-1-like proteins. Fpr1 belongs to a gene family that has expanded in plant pathogenic Sordariomycetes. These results suggest that secreted PR-1-like proteins play important roles in fungal pathogenicity.

Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC(90) values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC(90) was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC(50) for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC(90) for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.

Using a murine model of disseminated infection by two strains of Fusarium verticillioides, we have evaluated the efficacy of high doses of amphotericin B (AMB) (3 mg/kg of body weight/day), voriconazole (VRC) (60 mg/kg of body weight/day), posaconazole (PSC) (100 mg/kg of body weight/day), and the combinations of AMB plus VRC or PSC. In general, our results were very modest. Neither combination was superior to the respective monotherapies. VRC alone and in combination with AMB was able to prolong survival but not to reduce tissue burden, and AMB plus PSC was able to reduce fungal load in organs but not to prolong survival.

Using a murine model of disseminated infection by Fusarium verticillioides, the efficacy of liposomal amphotericin (L-AmB) B at 10mg/kg body weight once daily and terbinafine (TRB) at 150 mg/kg body weight twice daily, alone and in combination, was evaluated. The combination of L-AmB with TRB was the only treatment able to prolong survival and to reduce fungal loads in the spleen and kidneys of mice infected with either strain of F. verticillioides used. The results suggest that this combination may have a role in the treatment of F. verticillioides infection., (Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objectives: The aim of this study was to determine the genetic variability of clinical isolates morphologically identified as Fusarium oxysporum and to assess if there are differences in antifungal susceptibility among the possible genetic clades obtained., Methods: Twenty-eight isolates were molecularly characterized by sequence analysis of the elongation factor 1alpha gene. The antifungal susceptibilities of these isolates to 11 antifungal drugs were tested using a microdilution method., Results: and conclusions We obtained four different phylogenetic clades in the molecular study. Although all the antifungals tested showed poor activity against all the genetic clades, terbinafine showed the best results.

Forty-eight Fusarium isolates morphologically identified as belonging to seven species of clinical interest (i.e., Fusarium chlamydosporum, Fusarium dimerum, Fusarium incarnatum, Fusarium napiforme, Fusarium nygamai, Fusarium proliferatum, and Fusarium sacchari) were characterized molecularly by the analysis of the sequences of the TUB region of the beta-tubulin gene. F. chlamydosporum and F. dimerum were the most genetically heterogeneous species. A high degree of correlation between the morphological and molecular identification was shown among the isolates studied. A table with the key morphological features for the identification of these Fusarium species is provided. The antifungal susceptibilities of the Fusarium isolates to 11 antifungal drugs were tested; terbinafine was the most active drug against all the species tested with the exception of F. incarnatum, for which amphotericin B was the most active.

Objectives: We evaluated the efficacy of voriconazole, amphotericin B and micafungin alone and combined in a murine model of disseminated infection by Fusarium solani., Methods: Immunosuppressed mice were treated with voriconazole at 60 mg/kg/day, amphotericin B at 3 mg/kg/day, micafungin at 10 mg/kg/day or combinations of these antifungal drugs. For survival studies, treatment began 1 day after infection and continued for 10 days. For tissue burden studies, animals were sacrificed on day 6 of the treatment and the fungal load in the kidneys and spleens was measured. The experiments were carried out using two different clinical strains of F. solani., Results: Only the combination of voriconazole plus amphotericin B prolonged the survival of the mice versus the controls for the two strains tested. However, this combination only reduced tissue burden in the kidney and spleen of mice infected by one strain. The other treatments were clearly less effective., Conclusions: Voriconazole plus amphotericin B may have a role in the treatment of fusariosis.

Knockout mutants of Fusarium oxysporum lacking the putative photoreceptor Wc1 were impaired in aerial hyphae, surface hydrophobicity, light-induced carotenogenesis, photoreactivation after UV treatment, and upregulation of photolyase gene transcription. Infection experiments with tomato plants and immunodepressed mice revealed that Wc1 is dispensable for pathogenicity on plants but required for full virulence on mammals.

A microdilution method was used to test 11 antifungal drugs against clinical isolates of Fusarium thapsinum and three different phylogenetic clades of Fusarium verticillioides that were characterized by sequencing a region of the beta-tubulin gene. Terbinafine was the most-active drug against both species, followed by posaconazole against F. verticillioides.

Rho-type GTPases regulate polarized growth in yeast by reorganization of the actin cytoskeleton and through signalling pathways that control the expression of cell wall biosynthetic genes. We report the cloning and functional analysis of rho1 from Fusarium oxysporum, a soilborne fungal pathogen causing vascular wilt on plants and opportunistic infections in humans. F. oxysporum strains carrying either a Deltarho1 loss-of-function mutation or a rho1(G14V) gain-of-function allele were viable, but displayed a severely restricted colony phenotype which was partially relieved by the osmotic stabilizer sorbitol, indicating structural alterations in the cell wall. Consistent with this hypothesis, Deltarho1 strains showed increased resistance to cell wall-degrading enzymes and staining with Calcofluor white, as well as changes in chitin and glucan synthase gene expression and enzymatic activity. Re-introduction of a functional rho1 allele into the Deltarho1 mutant fully restored the wild-type phenotype. The Deltarho1 strain had dramatically reduced virulence on tomato plants, but was as virulent as the wild type on immunodepressed mice. Thus, Rho1 plays a key role during fungal infection of plants, but not of mammalian hosts.

Eleven antifungal drugs were tested against representative isolates of the four phylogenetic clades of the Fusarium solani species complex obtained in a multilocus sequence analysis. They all showed very poor activity, with no differences among the clades. Amphotericin B was the most active drug.

The filamentous fungus Fusarium oxysporum causes vascular wilt on a wide range of plant species and is an emerging pathogen of humans. A mitogen-activated protein kinase, Fmk1, and a G protein beta subunit, Fgb1, control pathogenicity of F. oxysporum on plants through distinct signalling pathways. In the present report, we studied the genetic interaction between fmk1 and fgb1 and their role in virulence on a mammalian host. The delta fmk1 or delta fgb1 single mutants exhibited similar virulence patterns as the wild type strain in an immunodepressed mouse model. By contrast, double mutants lacking both genes had dramatically reduced virulence. All mutants showed similar in vitro growth or tolerance to temperature and osmotic stress as the wild type strain. However, the delta fgb1 and delta fmk1 strains were reduced in specific extracellular protease activity or adhesion to fibronectin, respectively, two factors previously associated with fungal virulence. Thus, Fmk1 and Fgb1 are components of distinct signalling pathways which collectively control virulence of F. oxysporum on mammalian hosts.

Foot infections are common and serious complications of diabetic patients. We report the case of a 68-year-old patient with a diabetic foot infection that developed into a gangrenous necrosis. Fusarium spp. was isolated on two successive occasions with no other associated microorganisms. Histopathology demonstrated invasion of the fungus into the tisssue. These findings suggested an infection rather than colonization. A detailed morphological study showed that the isolate was Fusarium acutatum, which was confirmed by rDNA sequencing. This fungus is found only in Asia and has not been previously reported as a human pathogen.

In a retrospective study performed over 6 years in Brazil, Fusarium solani was found to be the most common species causing mycotic keratitis. The genetic diversity of 44 isolates from 39 patients was assessed by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and PCR restriction fragment length polymorphism (PCR-RFLP) fingerprinting. ERIC-PCR was more discriminatory than PCR-RFLP for differentiating the strains. By combining of the results of both techniques, we identified 40 genotypes. Molecular typing revealed a high genomic heterogeneity of the strains of F. solani studied.

Fungal pathogens cause disease in plant and animal hosts. The extent to which infection mechanisms are conserved between both classes of hosts is unknown. We present a dual plant-animal infection system based on a single strain of Fusarium oxysporum, the causal agent of vascular wilt disease in plants and an emerging opportunistic human pathogen. Injection of microconidia of a well-characterized tomato pathogenic isolate (isolate 4287) into the lateral tail vein of immunodepressed mice resulted in disseminated infection of multiple organs and death of the animals. Knockout mutants in genes encoding a mitogen-activated protein kinase, a pH response transcription factor, or a class V chitin synthase previously shown to be implicated in virulence on tomato plants were tested in the mouse model. The results indicate that some of these virulence factors play functionally distinct roles during the infection of tomato plants and mice. Thus, a single F. oxysporum strain can be used to study fungal virulence mechanisms in plant and mammalian pathogenesis.

We have studied the in vitro interactions of amphotericin B (AMB) with terbinafine (TBF), itraconazole, voriconazole (VCZ), albaconazole, and ravuconazole (RVZ), as well as TBF combined with the same azoles, against 11 isolates of Fusarium spp. using the fractional inhibitory concentration index. The highest percentage of synergistic interactions was observed for the combinations AMB-RVZ, TBF-VCZ, and TBF-RCZ.

Fusarium polyphialidicum caused a corneal ulcer in a Spanish man. Diagnosis was established by a histopathological study and repeated cultures. The isolate was clearly resistant in vitro to the antifungal agents tested. This is the first case of human or animal mycosis by this rare fungus.

This article is to alert medical mycologists and infectious disease specialists of recent name changes of medically important species of the filamentous mold FusariumFusarium species can cause localized and life-threating infections in humans. Of the 70 Fusarium species that have been reported to cause infections, close to one-third are members of the Fusarium solani species complex (FSSC), and they collectively account for approximately two-thirds of all reported Fusarium infections. Many of these species were recently given scientific names for the first time by a research group in the Netherlands, but they were misplaced in the genus Neocosmospora In this paper, we present genetic arguments that strongly support inclusion of the FSSC in Fusarium There are potentially serious consequences associated with using the name Neocosmospora for Fusarium species because clinicians need to be aware that fusaria are broadly resistant to the spectrum of antifungals that are currently available.

Any strategy that proposes solutions to health-related problems recognizes that people, animals, and the environment are interconnected. Fusarium is an example of this interaction because it is capable of infecting plants, animals, and humans. This review provides information on various aspects of these relations and proposes how to approach fusariosis with a One Health methodology (a multidisciplinary, and multisectoral approach that can address urgent, ongoing, or potential health threats to humans, animals, and the environment). Here, we give a framework to understand infection pathogenesis, through the epidemiological triad, and explain how the broad utilization of fungicides in agriculture may play a role in the treatment of human fusariosis. We assess how plumbing systems and hospital environments might play a role as a reservoir for animal and human infections. We explain the role of antifungal resistance mechanisms in both humans and agriculture. Our review emphasizes the importance of developing interdisciplinary research studies where aquatic animals, plants, and human disease interactions can be explored through coordination and collaborative actions. [ABSTRACT FROM AUTHOR]

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