J. Fungi, Volume 4, Issue 2 (June 2018) – 33 articles

Species of Scedosporium and Fusarium are considered emerging opportunistic pathogens, causing invasive fungal diseases in humans that are known as scedosporiosis and fusariosis, respectively. These mold infections typically affect patients with immune impairment; however, cases have been reported in otherwise healthy individuals. Clinical manifestations vary considerably, ranging from isolated superficial infection to deep-seated invasive infection—affecting multiple organs—which is often lethal. While there have been a number of advances in the detection of these infections, including the use of polymerase chain reaction (PCR) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS), diagnosis is often delayed, leading to substantial morbidity and mortality. Although the optimal therapy is controversial, there have also been notable advances in the treatment of these diseases, which often depend on a combination of antifungal therapy, reversal of immunosuppression, and in some cases, surgical resection. In this paper, we review these advances and examine how the management of scedosporiosis and fusariosis may change in the near future. Full article

The large increase in the population of immunosuppressed patients, coupled with the limited efficacy of existing antifungals and rising resistance toward them, have dramatically highlighted the need to develop novel drugs for the treatment of invasive fungal infections. An attractive possibility is the identification of possible drug targets within essential fungal metabolic pathways not shared with humans. Here, we review the vitamin biosynthetic pathways (vitamins A–E, K) as candidates for the development of antifungals. We present a set of ranking criteria that identify the vitamin B2 (riboflavin), B5 (pantothenic acid), and B9 (folate) biosynthesis pathways as being particularly rich in new antifungal targets. We propose that recent scientific advances in the fields of drug design and fungal genomics have developed sufficiently to merit a renewed look at these pathways as promising sources for the development of novel classes of antifungals. Full article

Seed persistence in the soil is threatened by microorganisms, but the seed coat helps protect the seed from them. Although modern rice (Oryza sativa L.) cultivars have a whitish caryopsis, some varieties have a red caryopsis coat, a trait typical of wild Oryza species. The red colour is due to the oxidation of proanthocyanidins, a class of flavonoids that is found in the outer layers of the seed in many species. We aimed to assess whether these natural compounds (proanthocyanidins and proanthocyanidin-derived pigment) have some protective effect against microbial attacks. Dehulled caryopses of white-grained and red-grained rice genotypes were employed to assay fungal infection. Specifically, three white-grained rice cultivars (Perla, Augusto, and Koral) and three red-grained rice varieties (Perla Rosso, Augusto Rosso, and Koral Rosso) were used. In a first test, the caryopses were infected with Epicoccum nigrum at 10 °C, and seedling growth was then assessed at 30 °C. In a second test, the degree of infection by the mycotoxigenic fungus Fusarium sporotrichioides was assayed by measuring the accumulation of T-2/HT-2 toxins in the caryopses. Infection was performed at 10 °C to prevent rice germination while allowing fungal growth. In both the tests, red caryopses showed reduced, or delayed, infection with respect to white ones. One black-grained cultivar (Venere) was assayed for the accumulation of T-2/HT-2 toxins as well, with results corresponding to those of the red-grained rice varieties. We argue that the red pigment accumulating in the caryopsis coat, and/or the proanthocyanidins associated with it, provides a protective barrier against challenging microorganisms. Full article

There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC₅₀ < 10 μg·mL⁻¹) with three fungi including Paecilomyces lilacinus (IC₅₀ = 0.44 μg·mL⁻¹), Penicillium janthinellum (IC₅₀ = 0.2 μg·mL⁻¹), and Paecilomyces sp. (IC₅₀ = 0.55 μg·mL⁻¹) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing. Full article

Certain endophytic fungi belonging to the Hypoxylon genus have recently been found to produce volatile organic compounds (VOCs) that have potential relevance as hydrocarbon fuels. Here, a recently discovered Hypoxylon sp. (BS15) was demonstrated to also produce VOCs, but with diminished VOC production after an extended period of in vitro growth. Restoring VOC production was partially achieved by growing BS15 in growth media containing finely ground woody tissue from the original host plant (Taxodium distichum). In an effort to isolate VOC production modulators, extracts from this woody tissue were made by sequentially extracting with dichloromethane, methanol, and water. Both the dichloromethane and water extracts were found to modulate VOC production, while the methanol extract had no effect. Surprisingly, the woody tissue remaining after exhaustive extraction was also shown to act as a VOC production modulator when included in the growth media, with changes observed in the production of four compounds. This woody tissue also induced production of two compounds not observed in the original BS15 extract. Filter paper had the same modulating effect as exhaustively extracted woody tissue, suggesting the modulation was perhaps due to cellulose degradation products. Overall, this study demonstrated that VOC production in BS15 can be influenced by multiple compounds in the woody tissue rather than a single modulator. Full article

Fungal species undergo many morphological transitions to adapt to changing environments, an important quality especially in fungal pathogens. For decades, Candida albicans has been one of the most prevalent human fungal pathogens, and recently, the prevalence of Candida tropicalis as a causative agent of candidiasis has increased. In C. albicans, the ability to switch between yeast and hyphal forms is thought to be a key virulence factor and is regulated by multiple signaling cascades—including the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), calcineurin, high-osmolarity glycerol (HOG), and mitogen-activated protein kinases (MAPK) signaling pathways—upon receiving environmental cues. The cAMP/PKA signaling pathway also triggers white-opaque switching in C. albicans. However, studies on C. tropicalis morphogenesis are limited. In this minireview, we discuss the regulation of the yeast-hypha transition, virulence, and white-opaque switching through the cAMP/PKA pathway in the closely related species C. albicans and C. tropicalis. Full article

Candida glabrata is the second most common cause of candidemia, and its ability to adhere to different host cell types, to microorganisms, and to medical devices are important virulence factors. Here, we consider three characteristics that confer extraordinary advantages to C. glabrata within the host. (1) C. glabrata has a large number of genes encoding for adhesins most of which are localized at subtelomeric regions. The number and sequence of these genes varies substantially depending on the strain, indicating that C. glabrata can tolerate high genomic plasticity; (2) The largest family of CWPs (cell wall proteins) is the EPA (epithelial adhesin) family of adhesins. Epa1 is the major adhesin and mediates adherence to epithelial, endothelial and immune cells. Several layers of regulation like subtelomeric silencing, cis-acting regulatory regions, activators, nutritional signaling, and stress conditions tightly regulate the expression of many adhesin-encoding genes in C. glabrata, while many others are not expressed. Importantly, there is a connection between acquired resistance to xenobiotics and increased adherence; (3) Other subfamilies of adhesins mediate adherence to Candida albicans, allowing C. glabrata to efficiently invade the oral epithelium and form robust biofilms. It is noteworthy that every C. glabrata strain analyzed presents a unique pattern of CWPs at the cell surface. Full article

The oral cavity serves as a nutrient-rich haven for over 600 species of microorganisms. Although many are essential to maintaining the oral microbiota, some can cause oral infections such as caries, periodontitis, mucositis, and endodontic infections, and this is further exacerbated with dental implants. Most of these infections are mixed species in nature and associated with a biofilm mode of growth. Here, after optimization of different parameters including cell density, growth media, and incubation conditions, we have developed an in vitro model of C. albicans–S. gordonii mixed-species biofilms on titanium discs that is relevant to infections of peri-implant diseases. Our results indicate a synergistic effect for the development of biofilms when both microorganisms were seeded together, confirming the existence of beneficial, mutualistic cross-kingdom interactions for biofilm formation. The morphological and architectural features of these dual-species biofilms formed on titanium were determined using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Mixed biofilms formed on titanium discs showed a high level of resistance to combination therapy with antifungal and antibacterial drugs. This model can serve as a platform for further analyses of complex fungal/bacterial biofilms and can also be applied to screening of new drug candidates against mixed-species biofilms. Full article

Four endophytic fungi were isolated from the medicinal plant, Catharanthus roseus, and were identified as Diaporthe spp. with partial translation elongation factor 1-alpha (TEF1), beta-tubulin (TUB), histone H3 (HIS), calmodulin (CAL) genes, and rDNA internal transcribed spacer (ITS) region (TEF1-TUB-HIS--CAL-ITS) multigene phylogeny suggested for species delimitation in the Diaporthe genus. Each fungus produces a unique mixture of volatile organic compounds (VOCs) with an abundant mixture of terpenoids analyzed by headspace solid-phase microextraction (SPME) fiber-GC/MS. These tentatively-detected terpenes included α-muurolene, β-phellandrene, γ-terpinene, and α-thujene, as well as other minor terpenoids, including caryophyllene, patchoulene, cedrene, 2-carene, and thujone. The volatile metabolites of each isolate showed antifungal properties against a wide range of plant pathogenic test fungi and oomycetes, including Alternaria alternata, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, and Phytophthora cinnamomi. The growth inhibition of the pathogens varied between 10% and 60% within 72 h of exposure. To our knowledge, the endophytic Diaporthe-like strains are first reported from Catharanthus roseus. VOCs produced by each strain of the endophytic Diaporthe fungi were unique components with dominant monoterpenes comparing to known Diaporthe fungal VOCs. A discussion is presented on the inhibitive bioactivities of secondary metabolites among endophytic Diaporthe fungi and this medicinal plant. Full article

Sporotrichosis is a subcutaneous mycosis that has re-emerged in several tropical and subtropical regions over the last decades. Growing findings suggest that the interplay of host, pathogen, and environment has a determinant effect on the diversity, local distribution, and virulence of Sporothrix schenckii sensu lato, the etiologic agent. Among the environmental factors, we have studied the potential role of repeated exposures to mercury (Hg), a known immunotoxic xenobiotic that is widely used in gold mining regions where sporotrichosis outbreaks are frequently reported. In this study, male Swiss mice received subcutaneous injections of either 300 or 1200 µg/kg of mercury (II) chloride (HgCl₂) for 14 days, three times a week. A control group was injected with the vehicle Phosphate Buffered Saline (PBS). Treatment with HgCl₂ impaired several immunologic parameters that are involved in host response to Sporothrix infection, such as the production of TNFα, IL-1, and nitric oxide by macrophages, and Th1/Th2/Th17 populations and their respective cytokines. The consequences of these effects on the host resistance to S. schenckii infection were subsequently evaluated. Hg-exposed mice exhibited a higher fungal load in the fungal inoculation site associated to systemic dissemination to spleen and liver on 14 days post-infection and a higher production of specific IgG1 and mild reduction of IgG2a. These findings suggest that repeated exposition to Hg enhances susceptibility to S. schenckii infection in mice and can be a factor associated to sporotrichosis outbreaks in endemic and highly Hg-polluted areas. Full article

Fusarium spp. and Alternaria spp., two genera of filamentous fungi, are common colonizers of the wheat phyllosphere. Both can be pathogenic and produce mycotoxins that are harmful to consumers. Their in-field infection dynamics have been a focus for the development of new control strategies. We analysed the abundance on plant ears and spore deposition patterns of Fusarium spp. and Alternaria spp. in a topographically heterogeneous field. Abundances were assessed genetically, using qPCR-based techniques, and passive spore traps were installed for quantifying the spore deposition at different plant heights. Data loggers were placed to measure the differences in microclimate across the field. Results indicate different distribution and spore deposition patterns for the two fungi. Fusarium spp. spore and genetic abundances were higher in spots with a more humid and colder under-canopy microclimate. Alternaria spp. showed the opposite trend for genetic abundance, while its spore deposition was not correlated to any of the microclimatic conditions and was more uniform across the field. Our study extends the knowledge on the dispersal and in-field infection dynamics of Fusarium spp. and Alternaria spp., important for a better understanding of the epidemiology of these wheat pathogens. It also illustrates that topographically heterogeneous fields are a suitable environment for studying the ecology of phyllosphere-colonizing fungi. Full article

Sporotrichosis is a cosmopolitan, chronic granulomatous mycosis, acquired by traumatic inoculation and caused by Sporothrix schenckii complex. Several methods of diagnostic are available, from KOH to molecular biology. In this review, we describe from the simplest (clinical diagnosis) to the most advanced diagnostic techniques (molecular biology). Full article

Despite efforts to address the burden of fungal infections in Malawi, the prevalence and incidence remain largely unknown. We assessed the annual burden in the general population and among populations at high risk and fungal infection frequencies in each particular population to estimate the national incidence or prevalence. The Malawi population is approximately 17.7 million (2017), with 48% under 15 years of age. Approximately 8% of the population is HIV positive. The most common infections are present in HIV/AIDS patients, with oral candidiasis being the commonest. Life threatening infections among those with AIDS patients include cryptococcal meningitis (8200 cases) and Pneumocystis pneumonia (3690 cases). Pulmonary TB is common, but extra pulmonary TB is rare; an estimated 2329 people have chronic pulmonary aspergillosis after TB. Asthma is a significant problem in Malawi, with an estimated 680,000 adults affected (4.67%) and 14,010 cases of allergic bronchopulmonary aspergillosis (ABPA). Tinea capitis is estimated to be present in over 670,000 young people (21% of school age children). The annual incidence of fungal keratitis is difficult to estimate, but as cases are frequently seen in the eye department, is likely to be a minimum of 1825 (10.3/100,000) cases. Among the most serious infections, cryptococcal meningitis and Pneumocystis pneumonia are top of the list. Overall, some 1,338,523 (7.54%) people are affected by a serious fungal infection in Malawi. These basic estimates are limited, due to poor record keeping, and require epidemiological studies to validate or modify the substantial burden estimates. National surveillance of fungal infections is urgently needed. Full article

The human fungal pathogen Candida glabrata is causing more and more problems in hospitals, as this species shows an intrinsic antifungal drug resistance or rapidly becomes resistant when challenged with antifungals. C. glabrata only grows in the yeast form, so it is lacking a yeast-to-hyphae switch, which is one of the main virulence factors of C. albicans. An important virulence factor of C. glabrata is its capacity to strongly adhere to many different substrates. To achieve this, C. glabrata expresses a large number of adhesin-encoding genes and genome comparisons with closely related species, including the non-pathogenic S. cerevisiae, which revealed a correlation between the number of adhesin-encoding genes and pathogenicity. The adhesins are involved in the first steps during an infection; they are the first point of contact with the host. For several of these adhesins, their importance in adherence to different substrates and subsequent biofilm formation was demonstrated in vitro or in vivo. In this review, we provide an overview of the role of C. glabrata adhesins during adhesion and biofilm formation both, under in vitro and in vivo conditions. Full article

There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from the six other fungal phyla are only sparsely described in the literature. In these other phyla, most of the research is at the cellular level, rather than at the molecular level, so there has been little characterization of the adhesion molecules themselves. A catalog of known adhesins shows some common features: high Ser/Thr content, tandem repeats, N- and O-glycosylations, GPI anchors, dibasic sequence motifs, and potential amyloid-forming sequences. However, none of these features is universal. Known ligands include proteins and glycans on homologous cells and host cells. Existing and novel tools can exploit the availability of genome sequences to identify and characterize new fungal adhesins. These include bioinformatics tools and well-established yeast surface display models, which could be coupled with an adhesion substrate array. Thus, new knowledge could be exploited to answer key questions in fungal ecology, animal and plant pathogenesis, and roles of biofilms in infection and biomass turnover. Full article

Fungal endophytes are diverse and widespread symbionts that occur in the living tissues of all lineages of plants without causing evidence of disease. Culture-based and culture-free studies indicate that they often are abundant in the leaves of woody angiosperms, but only a few studies have visualized endophytic fungi in leaf tissues, and the process through which most endophytes colonize leaves has not been studied thoroughly. We inoculated leaf discs and the living leaves of a model woody angiosperm, Populus trichocarpa, which has endophytes that represent three distantly-related genera (Cladosporium, Penicillium, and Trichoderma). We used scanning electron microscopy and light microscopy to evaluate the timeline and processes by which they colonize leaf tissue. Under laboratory conditions with high humidity, conidia germinated on leaf discs to yield hyphae that grew epiphytically and incidentally entered stomata, but did not grow in a directed fashion toward stomatal openings. No cuticular penetration was observed. The endophytes readily colonized the interiors of leaf discs that were detached from living leaves, and could be visualized within discs with light microscopy. Although they were difficult to visualize within the interior of living leaves following in vivo inoculations, standard methods for isolating foliar endophytes confirmed their presence. Full article

As is true with animal species, plants also have an associated microflora including endophytes as well as microbes associated with the phyllosphere and rhizosphere (plant surfaces) and this is considered the plant microbiome. However, those organisms within virtually all tissues and organs of the plant are known as endophytes. Most often fungi are the most frequently recovered endophytes from plant tissues, but bacterial forms generally occur in greater numbers, but not in species varieties. The exact biological/biochemical role of the endophyte in the plant and how it interacts with the plant and other endophytes and plant associated organisms has not been intensely and carefully examined. However, this has not stopped investigators in exploring the direct utility of endophytes in boosting plant production, and discovering that endophytes can directly influence the plant to resist temperature extremes, drought, as well as the presence of disease causing organisms. Also, because of the relationships that endophytes seem to have with their host plants, they make a myriad of biologically active compounds some of which are classified as antibiotics, antioxidants, anticancer agents, volatile antimicrobial agents, immunosuppressive compounds, plant growth promoting agents, and insecticides. These endophytic compounds represent a wide range of organic molecules including terpenoids, peptides, carbohydrates, aromatics, hydrocarbons and others and it seems that these compounds may have a role in the host microbe relationship. Most recently and quite surprisingly, some endophytes have been discovered that make hydrocarbons of the types found in diesel and gasoline fuels. In addition, recently discovered are epigenetic factors relating to the biology and biochemistry of endophytes. Interestingly, only about 1–2% of the entire spectrum of 300,000 known plants have been studied for their endophyte composition. Additionally, only a few plants have ever been completely studied including all tissues for the microbes within them. Likewise, the vast majority of plants, including those in oceans and lower plant forms, have never been examined for their endophytes. Furthermore, endophytes representing the “microbiome” of world’s major food plants as they exist in their native “centers of origin” are largely unknown. This non-classical review is intended to provide background information on aspects of developments in endophyte biology and more importantly the identification of new questions in this field that need to be addressed. The review is primarily based on the author’s long held experience in this field. Full article

Nodular lymphangitis, also known as sporotrichoid lymphocutaneous infections, is characterized by suppurative inflammatory nodules along the lymphatic vessels. This manifestation is classic of sporotrichosis, however, other infections such as nocardiosis, atypical mycobacteriosis, leishmaniasis, among others, can also express this clinical pattern. Sporotrichosis, which often occurs in gardeners, remains the most recognized cause of nodular lymphangitis. The histopathological studies, as well as the culture are diagnostic standards of lesions that do not respond to empirical treatment. In this article, we will review the main causes of nodular lymphangitis or lymphocutaneous sporotrichoid infections. Full article

Sporotrichosis is the most common implantation mycosis caused by several species of the Sporothrix schenckii complex. The gold standard for diagnosis is concerned with the isolation of the fungus; although, fresh examinations, staining, and biopsies are also helpful for this purpose. The sporotrichin is an antigenic complex comprised of a peptide-rhamnomannan, which is relevant with respect to pathogenic fungi; it is primarily used for serological and skin testing. We present a study regarding the use of sporotrichin as a diagnostic aid for cutaneous sporotrichosis. Furthermore, 138 cases with suspicion of sporotrichosis were included, 55 of which were proven through cultures. Moreover, out of these 55 cases, 52 (94.5%) tested positive for sporotrichin, while the negative cases corresponded to the disseminated cutaneous forms. We observed a sensitivity of 94.5% and a specificity of 95.2%. We consider that the use of sporotrichin as a skin test helps us as an auxiliary diagnosis before a positive sample culture. Full article

Curvularia protuberata, an endophytic fungus in the Ascomycota, provides plants with thermotolerance only when it carries a mycovirus known as Curvularia thermotolerance virus (CThTV), and forms a three-way symbiotic relationship among these organisms. Under heat stress, several genes are expressed differently between virus-free C. protuberata (VF) and C. protuberata carrying CThTV (AN). We developed an expression vector, pM2Z-fun, carrying a zeocin resistance gene driven by the ToxA promoter, to study gene functions in C. protuberata to better understand this three-way symbiosis. Using this new 3.7-kb vector, five genes that are differentially expressed in C. protuberata—including genes involved in the trehalose, melanin, and catalase biosynthesis pathways—were successfully overexpressed or downregulated in VF or AN C. protuberata strains, respectively. The VF overexpression lines showed higher metabolite and enzyme activity than in the control VF strain. Furthermore, downregulation of expression of the same genes in the AN strain resulted in lower metabolite and enzyme activity than in the control AN strain. The newly generated expression vector, pM2Z-fun, has been successfully used to express target genes in C. protuberata and will be useful in further functional expression studies in other Ascomycota fungi. Full article

The genus Artemisia, a collection of ~400 hardy herbaceous plant and shrub species, is an important resource contributing to chemistry, medicine, agriculture, industry, and ecology. Its communities of endophytic fungi have only recently begun to be explored. Summarized from studies conducted on the fungal endophytes in Artemisia species, both fungal phylogenetic diversity and the associated bioactivity was examined. Isolations from 14 species of Artemisia have led to 51 genera of fungal endophytes, 28 families, and 18 orders. Endophytes belonged mainly to Ascomycota, except for two taxa of Cantharellales and Sporidiobolales, one taxon of Mucoromycota, and one species of Oomycota. The mostly common families were Pleosporaceae, Trichocomaceae, Leptosphaeriaceae, and Botryosphaeriaceae (relative abundance = 14.89, 8.51, 7.14 and 6.38, respectively). In the search for bioactive metabolites, 27 novel compounds were characterized and 22 metabolites were isolated between 2006 and 2017. The first study on endophytic fungi isolated from species of Artemisia was published but 18 years ago. This summary of recently acquired data illustrates the considerable diversity of biological purposes addressed by fungal endophytes of Artemisia spp. Full article

Pleurotus is considered an important genus that belongs to the family Pleurotaceae and includes the edible King Oyster mushroom (Pleurotus eryngii). In the present study, 19 Pleurotus isolates were collected from two locations in the north of Jordan (Tell ar-Rumman and Um-Qais). The morphological characteristics among collected isolates revealed that there was a morphological similarity among the collected isolates. Nucleotide sequence analysis of the internal transcribed spacer (ITS1–5.8S rDNA–ITS4 region) and 28S nuclear large subunit (nLSU) in the ribosomal DNA gene of the isolated stains showed that all of them share over 98% sequence similarity with P. eryngii. Genetic diversity among the collected strains was assessed using inter simple sequence repeat (ISSR) analysis using 18 different primer pairs. Using this approach, 141 out of 196 bands obtained were considered polymorphic and the highest percentage of polymorphism was observed using primer UBC827 (92.3%) with an overall Polymorphism Information Content (PIC) value of 70.56%. Cluster analysis showed that the Jordanian Pleurotus isolates fall into two main clades with a coefficient of similarity values ranging from 0.59 to 0.74 with a clear clustering based on collection sites. The results of the present study reveal that molecular techniques of ISSR and rDNA sequencing can greatly aid in classification and identification of Pleurotus spp. in Jordan. Full article

The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics were searched from multiple sources, local literature was identified, and estimates made. Some additional data were sourced from the Ministry of Health, the Global Initiative for Asthma (GINA) program, and national haematology and transplant societies. Argentina has a population of 43.8 million, with 25% of this total being children under 15 years. The predicted candidemia annual incidence is 2193 cases, with 50% occurring in the ICU. At a 6% prevalence rate, an estimated 593,695 women suffer from recurrent vulvovaginal candidiasis. Invasive aspergillosis is relatively common because of high smoking and chronic obstructive pulmonary disease (COPD) rates, with 268 cases in immunocompromised patients and another 1938 in the 168,000 COPD patients admitted to hospital. Asthma is also common, affecting 14% of adults, and so allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) are major problems. An estimated 432 cases of cryptococcal meningitis (CM)—90% of them in AIDS patients—and 1177 cases of Pneumocystis pneumonia (PCP) occur each year. The estimated annual case number of disseminated histoplasmosis is 404 in AIDS patients, almost as frequent as CM. Paracoccidioidomycosis annual incidence is estimated at 219, and coccidioidomycosis at 16 cases. At least 881,023 people (>2.01%) in Argentina are affected by a serious fungal disease annually, with considerable morbidity and mortality. Full article

Lipids, commonly including phospholipids, sphingolipids, fatty acids, sterols, and triacylglycerols (TAGs), are important biomolecules for the viability of all cells. Phospholipids, sphingolipids, and sterols are important constituents of biological membranes. Many lipids play important roles in the regulation of cell metabolism by acting as signaling molecules. Neutral lipids, including TAGs and sterol esters (STEs), are important storage lipids in cells. In view of the importance of lipid molecules, this review briefly summarizes the metabolic pathways for sterols, phospholipids, sphingolipids, fatty acids, and neutral lipids in fungi and illustrates the differences between fungal and human (or other mammalian) cells, especially in relation to lipid biosynthetic pathways. These differences might provide valuable clues for us to find target proteins for novel antifungal drugs. In addition, the development of lipidomics technology in recent years has supplied us with a shortcut for finding new antifungal drug targets; this ability is important for guiding our research on pathogenic fungi. Full article

Cryptococcosis, a fungal disease arising from the etiologic agent Cryptococcus neoformans, sickens a quarter of a million people annually, resulting in over 180,000 deaths. Interestingly, males are affected by cryptococcosis more frequently than females, a phenomenon observed for more than a half century. This disparity is seen in both HIV⁻ (~3M:1F) and HIV⁺ (~8M:2F) populations of cryptococcal patients. In humans, male sex is considered a pre-disposing risk factor for cryptococcosis and males suffering from the disease have more severe symptoms and poorer outcomes. There are numerous observational, clinical and epidemiological studies documenting the male disadvantage in C. neoformans but with no further explanation of cause or mechanism. Despite being commonly acknowledged, little primary research has been conducted elucidating the reasons for these differences. The research that has been conducted, however, suggests sex hormones are a likely cause. Given that the sex difference is both prevalent and accepted by many researchers in the field, it is surprising that more is not known. This review highlights the data regarding differences in sexual dimorphism in C. neoformans infections and suggests future directions to close the research gap in this area. Full article

White-nose syndrome (WNS) is caused by Pseudogymnoascus destructans, a psychrophilic fungus that infects hibernating bats and has caused a serious decline in some species. Natural aroma compounds have been used to control growth of fungal food storage pathogens, so we hypothesized that a similar strategy could work for control of P. destructans. The effectiveness of exposure to low concentrations of the vapor phase of four of these compounds was tested on mycelial plugs and conidiospores at temperatures of 5, 10 and 15 °C. Here we report the efficacy of vapor phase mushroom alcohol (1-octen-3-ol) for inhibiting mycelial and conidiospore growth of P. destructans at 0.4 and 0.8 µmol/mL and demonstrate that the R enantiomer of this compound is more effective than the S enantiomer, supporting the finding that biological systems can be sensitive to stereochemistry. Further, we report that vapor phase leaf aldehyde (trans-2-hexenal), a common aroma compound associated with cut grass odors and also the major volatile compound in extra virgin olive oil, is more effective than mushroom alcohol. At 0.05 µmol/mL, trans-2-hexenal is fungicidal to both conidiospores and mycelia of P. destructans. Full article

Considering the significance in survival and virulence, we have made an attempt to understand modulations in the membrane and cell wall properties of Candida albicans hyphae induced by temperature (37 °C) and neutral pH and yeast form cells grown under low hydrostatic pressure (LHP). Our results suggest that cell surface hydrophobicity (CSH) and adhesion are dynamic properties determined largely by the microenvironment rather than morphological forms, citing the significance of variation in niche specific virulence. GC-MS analysis showed that 49 and 41 fatty acids modulated under hyphal form induced by temperature alone (37 °C) and neutral pH, respectively while that of 58 under yeast form cells under low hydrostatic pressure (LHP) (1800 Pa). Fatty acid and ergosterol data indicates that fluidity increases with increase in temperature (37 °C) and neutral pH i.e., saturated fatty acids and ergosterol decreases. Similarly, CSH and adhesion decrease in response to temperature (37 °C), pH 7, and LHP compared to controls, irrespective of morphological forms. In general, membranes were more rigid, and cell walls were more hydrophobic and adhesive in yeast form compared to hyphal form cells, except in case of yeast form cells grown under LHP. Yeast form cells grown under LHP are less hydrophobic and adhesive. Full article

Mucormycosis is an emerging opportunistic fungal infection. Increasing immunocompromization, widespread use of antibacterial and antifungal agents (such as voriconazole prophylaxis), carcinomas, transplantation and lifestyle diseases such as diabetes are the main contributors to this situation. The predominant clinical manifestations of mucormycosis vary from host to host, with rhino-orbital-cerebral, pulmonary, cutaneous, and gastrointestinal infections being the most common. In India, the prevalence of mucormycosis is approximately 0.14 cases/1000 population, which is about 70 times the worldwide-estimated rate for mucormycosis. The present study was undertaken over a period of five years (January 2009–December 2014) to determine the prevalence of mucormycosis. The samples suspected of mucormycosis were examined by direct KOH wet mount and cultured on Sabouraud’s dextrose agar without actidione and on blood agar as per standard mycological techniques. Histopathological correlation was done for most of the cases. Antifungal susceptibility testing was performed by the EUCAST reference method. We identified a total of 82 cases of mucormycosis out of a total of 6365 samples received for mycological culture and examination during the said time period. Out of these, 56 were male patients and 27 were females. Most common presentation was rhino-orbito-cerebral (37), followed by cutaneous (25), pulmonary (14), oral cavity involvement (4) and gastrointestinal (2). The most common risk factors were diabetes and intramuscular injections. The fungi isolated were Rhizopus arrhizus (17), Apophysomyces variabilis (12), R. microsporus (9), Lichtheimia ramosa (8), Saksenaea erythrospora (5), Syncephalastrum racemosus (4), R. homothallicus (2), Rhizomucor pusillus (1), Mucor irregularis (1) and A. elegans (1). The mainstay of the treatment was amphotericin B, along with extensive surgical debridement whenever feasible. Most of the patients (50) recovered, but 25 died. The rest of the patients left against medical advice. “Nip in the Bud” should be the mantra for clinicians/surgeons for a favorable prognosis. Early diagnosis, prompt institution of appropriate antifungal therapy, surgical debridement whenever necessary, knowledge of risk factors and their timely reversal is the key for management. Full article

Invasive candidiasis is a common healthcare-associated infection with a high mortality rate that can exceed 60% in cases of septic shock. Blood culture performance is far from ideal, due to the long time to positivity and suppression by antifungal agents. The T2 Magnetic Resonance (T2MR) assay is an FDA-approved qualitative molecular diagnostic method that can detect and speciate the 5 most common Candida spp.; namely, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei, in approximately 5 h. In a multicenter clinical trial that included both a prospective and a contrived arm to represent the full range of clinically relevant concentrations of Candida spp., T2MR demonstrated a sensitivity and specificity of 91.1% and 98.1%, respectively. The utility of T2MR in candidemia depends on the prevalence of disease in each clinical setting. In intensive care units and other high-prevalence settings, the incorporation of T2MR in diagnostic algorithms is very appealing. T2MR is expected to allow timely initiation of antifungal therapy and help with anti-fungal stewardship. In low-prevalence settings, the positive predictive value of T2MR might not be enough to justify initiation of antifungal treatment in itself. The performance of T2MR has not been studied in cases of deep-seated candidiasis. Despite some promising evidence in published clinical trials, further studies are needed to determine the performance of T2MR in invasive candidiasis without candidemia. Overall, experience with T2MR in everyday clinical practice is evolving but, in the right setting, this technology is expected to provide “actionable information” for the management of patients evaluated for candidemia. Full article

Fungal infections are frequent in Cameroon, and invasive fungal infections are sometimes detected, usually in HIV-infected patients. For these reasons, we have estimated the burden of fungal infections. Using published literature and population estimates for the at-risk group, we used deterministic modelling to derive national incidence and prevalence estimates for the most serious fungal diseases. HIV infection is common and an estimated 120,000 have CD4 counts <200 × 10⁶/mL and commonly present with opportunistic infection. Oesophageal candidiasis in HIV is common, and in poorly controlled diabetics. We estimate 6720 cases of cryptococcal meningitis, 9000 of Pneumocystis pneumonia, 1800 of disseminated histoplasmosis annually complicating AIDS, and 1200 deaths from invasive aspergillosis in AIDS, but there are no data. We found that 2.4% of adults have chronic obstructive pulmonary disease (COPD) and 2.65% have asthma, with “fungal asthma” affecting 20,000. Chronic pulmonary aspergillosis probably affects about 5000 people, predominantly after tuberculosis but also with COPD and other lung diseases. Also, tinea capitis in schoolchildren is frequent. Overall, an estimated 1,236,332 people are affected by a serious fungal infection. There is an urgent need for government and clinician attention, improved laboratory facilities, fungal diagnostic tests, and competent laboratory technicians, as well as all World Health Organization (WHO)-endorsed essential antifungal drugs to be made available, as only fluconazole is registered and available in the country. Full article