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Applied Microbiology and Biotechnology Aug 2023Fungi are widely exploited for large-scale production in the biotechnological industry to produce a diverse range of substances due to their versatility and relative... (Review)
Review
Fungi are widely exploited for large-scale production in the biotechnological industry to produce a diverse range of substances due to their versatility and relative ease of growing on various substrates. The occurrence of a phenomenon-the so-called fungal strain degeneration-leads to the spontaneous loss or decline of production capacity and results in an economic loss on a tremendous scale. Some of the most commonly applied genera of fungi in the biotechnical industry, such as Aspergillus, Trichoderma, and Penicillium, are threatened by this phenomenon. Although fungal degeneration has been known for almost a century, the phenomenon and its underlying mechanisms still need to be understood. The proposed mechanisms causing fungi to degenerate can be of genetic or epigenetic origin. Other factors, such as culture conditions, stress, or aging, were also reported to have an influence. This mini-review addresses the topic of fungal degeneration by describing examples of productivity losses in biotechnical processes using Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, and Penicillium chrysogenum. Further, potential reasons, circumvention, and prevention methods are discussed. This is the first mini-review which provides a comprehensive overview on this phenomenon in biotechnologically used fungi, and it also includes a collection of strategies that can be useful to minimize economic losses which can arise from strain degeneration. KEY POINTS: • Spontaneous loss of productivity is evident in many fungi used in biotechnology. • The properties and mechanisms underlying this phenomenon are very versatile. • Only studying these underlying mechanisms enables the design of a tailored solution.
Topics: Aspergillus niger; Penicillium; Penicillium chrysogenum; Fungi; Aspergillus oryzae; Biotechnology; Trichoderma
PubMed: 37341752
DOI: 10.1007/s00253-023-12615-z -
Genes Nov 2019Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species and , which propagate primarily through clonal, asexual... (Review)
Review
Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species and , which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast . The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens and .
Topics: Adaptation, Physiological; Candida; Cryptococcus; Genomic Instability; Homologous Recombination; Mitosis
PubMed: 31703352
DOI: 10.3390/genes10110901 -
Journal of Hepatology Apr 2023Liver and biliary diseases affect more than a billion people worldwide, with high associated morbidity and mortality. The impact of the intestinal bacterial microbiome... (Review)
Review
Liver and biliary diseases affect more than a billion people worldwide, with high associated morbidity and mortality. The impact of the intestinal bacterial microbiome on liver diseases has been well established. However, the fungal microbiome, or mycobiome, has been overlooked for a long time. Recently, several studies have shed light on the role of the mycobiome in the development and progression of hepatobiliary diseases. In particular, the fungal genus Candida has been found to be involved in the pathogenesis of multiple hepatobiliary conditions. Herein, we compare colonisation and infection, describe mycobiome findings in the healthy state and across the various hepatobiliary conditions, and point toward communalities. We detail how quantitation of immune responses to fungal antigens can be employed to predict disease severity, e.g. using antibodies to Saccharomyces cerevisiae or specific anti-Candida albicans antibodies. We also show how fungal products (e.g. beta-glucans, candidalysin) activate the host's immune system to exacerbate liver and biliary diseases. Finally, we describe how the gut mycobiome can be modulated to ameliorate hepatobiliary conditions.
Topics: Humans; Mycobiome; Candida; Mycoses; Candida albicans; Saccharomyces cerevisiae; Digestive System Diseases
PubMed: 36565724
DOI: 10.1016/j.jhep.2022.12.006 -
Toxins Jan 2020Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin...
Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In total, 70.8% of herbs were slightly contaminated with aflatoxins (<5 μg kg). radix samples contained ochratoxin A (OTA) (360-515 μg kg), and Scutellariae radix samples contained OTA (49-231 μg kg) and citrinin (15-53 μg kg). Forty samples (83.3%) contained fungal contamination. Sixty-nine strains were characterized via morphological and molecular identification. The predominant mycoflora comprised four genera, spp. (26.1%), spp. (24.6%), spp. (14.5%), and spp. (11.6%). Aflatoxins, OTA, and citrinin were detected in 37 cultures by high-performance liquid chromatography-tandem mass spectrometry. Approximately 21.6% of and isolates produced mycotoxins. One strain isolated from radix synthesized citrinin. Multiplex PCR analysis showed that three strains harbored aflatoxin biosynthesis genes. One strain isolated from fructus produced AFB and AFB. To the best of our knowledge, the citrinin production by and was first reported in this study, which poses a potential risk of mycotoxin contamination in medicinal herbs.
Topics: Aflatoxins; Aspergillus; Aspergillus flavus; Citrinin; Food Contamination; Food Microbiology; Fungi; Mycotoxins; Ochratoxins; Penicillium; Plants, Medicinal
PubMed: 31947869
DOI: 10.3390/toxins12010030 -
Current Biology : CB Jul 2020Interspecific hybridization substantially alters genotypes and phenotypes and can give rise to new lineages. Hybrid isolates that differ from their parental species in...
Interspecific hybridization substantially alters genotypes and phenotypes and can give rise to new lineages. Hybrid isolates that differ from their parental species in infection-relevant traits have been observed in several human-pathogenic yeasts and plant-pathogenic filamentous fungi but have yet to be found in human-pathogenic filamentous fungi. We discovered 6 clinical isolates from patients with aspergillosis originally identified as Aspergillus nidulans (section Nidulantes) that are actually allodiploid hybrids formed by the fusion of Aspergillus spinulosporus with an unknown close relative of Aspergillus quadrilineatus, both in section Nidulantes. Evolutionary genomic analyses revealed that these isolates belong to Aspergillus latus, an allodiploid hybrid species. Characterization of diverse infection-relevant traits further showed that A. latus hybrid isolates are genomically and phenotypically heterogeneous but also differ from A. nidulans, A. spinulosporus, and A. quadrilineatus. These results suggest that allodiploid hybridization contributes to the genomic and phenotypic diversity of filamentous fungal pathogens of humans.
Topics: Aspergillus; Diploidy; Genome, Fungal; Genomics; Hybridization, Genetic
PubMed: 32502407
DOI: 10.1016/j.cub.2020.04.071 -
Genes Oct 2019Human fungal pathogens, such as , and , are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of... (Review)
Review
Human fungal pathogens, such as , and , are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the human body and cause life-threating infections relies on their capacity to adapt and thrive in diverse hostile host-niche environments. Stress-induced genome instability is a key adaptive strategy used by human fungal pathogens as it increases genetic diversity, thereby allowing selection of genotype(s) better adapted to a new environment. Heterochromatin represses gene expression and deleterious recombination and could play a key role in modulating genome stability in response to environmental changes. However, very little is known about heterochromatin structure and function in human fungal pathogens. In this review, I use our knowledge of heterochromatin structure and function in fungal model systems as a road map to review the role of heterochromatin in regulating genome plasticity in the most common human fungal pathogens: , and
Topics: Aspergillus fumigatus; Candida albicans; Chromatin Assembly and Disassembly; Cryptococcus neoformans; Gene Expression Regulation, Fungal
PubMed: 31661931
DOI: 10.3390/genes10110855 -
Microbial Cell Factories May 2024Multi resistant fungi are on the rise, and our arsenal compounds are limited to few choices in the market such as polyenes, pyrimidine analogs, azoles, allylamines, and... (Review)
Review
Multi resistant fungi are on the rise, and our arsenal compounds are limited to few choices in the market such as polyenes, pyrimidine analogs, azoles, allylamines, and echinocandins. Although each of these drugs featured a unique mechanism, antifungal resistant strains did emerge and continued to arise against them worldwide. Moreover, the genetic variation between fungi and their host humans is small, which leads to significant challenges in new antifungal drug discovery. Endophytes are still an underexplored source of bioactive secondary metabolites. Many studies were conducted to isolate and screen endophytic pure compounds with efficacy against resistant yeasts and fungi; especially, Candida albicans, C. auris, Cryptococcus neoformans and Aspergillus fumigatus, which encouraged writing this review to critically analyze the chemical nature, potency, and fungal source of the isolated endophytic compounds as well as their novelty features and SAR when possible. Herein, we report a comprehensive list of around 320 assayed antifungal compounds against Candida albicans, C. auris, Cryptococcus neoformans and Aspergillus fumigatus in the period 1980-2024, the majority of which were isolated from fungi of orders Eurotiales and Hypocreales associated with terrestrial plants, probably due to the ease of laboratory cultivation of these strains. 46% of the reviewed compounds were active against C. albicans, 23% against C. neoformans, 29% against A. fumigatus and only 2% against C. auris. Coculturing was proved to be an effective technique to induce cryptic metabolites absent in other axenic cultures or host extract cultures, with Irperide as the most promising compounds MIC value 1 μg/mL. C. auris was susceptible to only persephacin and rubiginosin C. The latter showed potent inhibition against this recalcitrant strain in a non-fungicide way, which unveils the potential of fungal biofilm inhibition. Further development of culturing techniques and activation of silent metabolic pathways would be favorable to inspire the search for novel bioactive antifungals.
Topics: Antifungal Agents; Endophytes; Humans; Microbial Sensitivity Tests; Cryptococcus neoformans; Fungi; Aspergillus fumigatus; Candida albicans
PubMed: 38822407
DOI: 10.1186/s12934-024-02411-3 -
PLoS Neglected Tropical Diseases Feb 2022Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum... (Review)
Review
BACKGROUND
Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities.
METHODS
A PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered.
FINDINGS
In the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration.
CONCLUSIONS
Despite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.
Topics: Africa; Animals; Awareness; Health Knowledge, Attitudes, Practice; Histoplasma; Histoplasmosis; Humans; Research
PubMed: 35202403
DOI: 10.1371/journal.pntd.0010111 -
Environmental Microbiology Reports Apr 2022Under natural environmental settings or in the human body, the majority of microorganisms exist in complex polymicrobial biofilms adhered to abiotic and biotic surfaces.... (Review)
Review
Under natural environmental settings or in the human body, the majority of microorganisms exist in complex polymicrobial biofilms adhered to abiotic and biotic surfaces. These microorganisms exhibit symbiotic, mutualistic, synergistic, or antagonistic relationships with other species during biofilm colonization and development. These polymicrobial interactions are heterogeneous, complex and hard to control, thereby often yielding worse outcomes than monospecies infections. Concerning fungi, Candida spp., in particular, Candida albicans is often detected with various bacterial species in oral biofilms. These Candida-bacterial interactions may induce the transition of C. albicans from commensal to pathobiont or dysbiotic organism. Consequently, Candida-bacterial interactions are largely associated with various oral diseases, including dental caries, denture stomatitis, periodontitis, peri-implantitis, and oral cancer. Given the severity of oral diseases caused by cross-kingdom consortia that develop hard-to-remove and highly drug-resistant biofilms, fundamental research is warranted to strategically develop cost-effective and safe therapies to prevent and treat cross-kingdom interactions and subsequent biofilm development. While studies have shed some light, targeting fungal-involved polymicrobial biofilms has been limited. This mini-review outlines the key features of Candida-bacterial interactions and their impact on various oral diseases. In addition, current knowledge on therapeutic strategies to target Candida-bacterial polymicrobial biofilms is discussed.
Topics: Biofilms; Candida; Candida albicans; Dental Caries; Humans; Symbiosis
PubMed: 35218311
DOI: 10.1111/1758-2229.13053 -
Cell Chemical Biology Jul 2023Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify antifungal compounds, we...
Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify antifungal compounds, we screened the RIKEN natural product depository against representative isolates of four major human fungal pathogens. This screen identified NPD6433, a triazenyl indole with broad-spectrum activity against all screening strains, as well as the filamentous mold Aspergillus fumigatus. Mechanistic studies indicated that NPD6433 targets the enoyl reductase domain of fatty acid synthase 1 (Fas1), covalently inhibiting its flavin mononucleotide-dependent NADPH-oxidation activity and arresting essential fatty acid biosynthesis. Robust Fas1 inhibition kills Candida albicans, while sublethal inhibition impairs diverse virulence traits. At well-tolerated exposures, NPD6433 extended the lifespan of nematodes infected with azole-resistant C. albicans. Overall, identification of NPD6433 provides a tool with which to explore lipid homeostasis as a therapeutic target in pathogenic fungi and reveals a mechanism by which Fas1 function can be inhibited.
Topics: Humans; Antifungal Agents; Candida albicans; Aspergillus fumigatus; Virulence; Microbial Sensitivity Tests
PubMed: 37369212
DOI: 10.1016/j.chembiol.2023.06.005