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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 -
Molecules (Basel, Switzerland) Oct 2022Marine fungi sp. is an important source of natural active lead compounds with biological and chemical diversity, of which sesquiterpenoids are an extremely important... (Review)
Review
Marine fungi sp. is an important source of natural active lead compounds with biological and chemical diversity, of which sesquiterpenoids are an extremely important class of bioactive secondary metabolites. In this paper, we review the sources, chemical structures, bioactivity, biosynthesis, and druggability evaluation of sesquiterpenoids discovered from marine fungi sp. since 2008. The species involved include mainly , , , , , and so on, which originate from sponges, marine sediments, algae, mangroves, and corals. In recent years, 268 sesquiterpenoids were isolated from secondary metabolites of marine sp., 131 of which displayed bioactivities such as antitumor, antimicrobial, anti-inflammatory, and enzyme inhibitory activity. Furthermore, the main types of active sesquiterpenoids are bisabolanes, followed by drimanes, nitrobenzoyl, etc. Therefore, these novel sesquiterpenoids will provide a large number of potential lead compounds for the development of marine drugs.
Topics: Animals; Aspergillus; Sesquiterpenes; Fungi; Anti-Infective Agents; Anthozoa
PubMed: 36364202
DOI: 10.3390/molecules27217376 -
Biomolecules Dec 2022belongs to the Aspergillus section Nidulantes. This species is found in soils and organisms from marine environments, such as jellyfishes and sponges. The first... (Review)
Review
belongs to the Aspergillus section Nidulantes. This species is found in soils and organisms from marine environments, such as jellyfishes and sponges. The first chemical study reported in the literature dates from 1970, with depsidones nidulin (), nornidulin (), and unguinol () being the first isolated compounds. Fifty-two years since this first study, the isolation and characterization of ninety-seven () compounds have been reported. These compounds are from different classes, such as depsides, depsidones, phthalides, cyclopeptides, indanones, diarylethers, pyrones, benzoic acid derivatives, orcinol/orsenillate derivatives, and sesterpenoids. In terms of biological activities, the first studies on isolated compounds from came only in the 1990s. Considering the tendency for antiparasitic and antibiotics to become ineffective against resistant microorganisms and larvae, compounds have also been extensively investigated and some compounds are considered very promising. In addition to these larvicidal and antimicrobial activities, these compounds also show activity against cancer cell lines, animal growth promotion, antimalarial and antioxidant activities. Despite the diversity of these compounds and reported biological activities, remains an interesting target for studies on metabolic induction to produce new compounds, the determination of new biological activities, medicinal chemistry, structural modification, biotechnological approaches, and molecular modeling, which have yet to be extensively explored.
Topics: Animals; Aspergillus; Anti-Infective Agents; Anti-Bacterial Agents; Models, Molecular
PubMed: 36551248
DOI: 10.3390/biom12121820 -
Microbiology Spectrum Jun 2023Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are...
Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are concerns for CPA patients. However, diagnostic practice is poorly evaluated, especially in resource-constrained areas where Aspergillus antibody testing tools are lacking. This study aimed to investigate the diagnostic laboratory findings in a retrospective CPA cohort and to evaluate the performance of a novel Aspergillus IgG lateral flow assay (LFA; Era Biology, Tianjin, China). During January 2016 and December 2021, suspected CPA patients were screened at the Center for Infectious Diseases at Huashan Hospital. A total of 126 CPA patients were enrolled. Aspergillus IgG was positive in 72.1% with chronic cavitary pulmonary aspergillosis, 75.0% with chronic necrotizing pulmonary aspergillosis, 41.7% with simple aspergilloma, and 30.3% with Aspergillus nodule(s). The cavitary CPA subtypes had significantly higher levels of Aspergillus IgG. Aspergillus IgG was negative in 52 patients, who were finally diagnosed by histopathology, respiratory culture, and metagenomic next-generation sequencing (mNGS). Sputum culture was positive in 39.3% (42/107) of patients and Aspergillus fumigatus was the most common species (69.0%, 29/42). For CPA cohort versus controls, the sensitivity and specificity of the LFA were 55.6% and 92.7%, respectively. In a subgroup analysis, the LFA was highly sensitive for A. fumigatus-associated chronic cavitary pulmonary aspergillosis (CCPA; 96.2%, 26/27). Given the complexity of the disease, a combination of serological and non-serological tests should be considered to avoid misdiagnosis of CPA. The novel LFA has a satisfactory performance and allows earlier screening and diagnosis of CPA patients. There are concerns on avoiding diagnostic delay and misdiagnosis for chronic pulmonary aspergillosis due to its high morbidity and mortality. A proportion of CPA patients test negative for Aspergillus IgG. An optimal diagnostic strategy for CPA requires in-depth investigation based on real-world diagnostic practice, which has been rarely discussed. We summarized the clinical and diagnostic laboratory findings of 126 CPA patients with various CPA subtypes. Aspergillus IgG was the most sensitive test for diagnosing CPA. However, it was negative in 52 patients, who were finally diagnosed by non-serological tests, including biopsy, respiratory culture, and metagenomic next-generation sequencing. We also evaluated a novel Aspergillus IgG lateral flow assay, which showed a satisfactory performance in cavitary CPA patients and was highly specific to Aspergillus fumigatus. This study gives a full picture of the diagnostic practice for CPA patients in Chinese context and calls for early diagnosis of CPA with combined approaches.
Topics: Humans; Retrospective Studies; Delayed Diagnosis; Pulmonary Aspergillosis; Aspergillus; Immunoglobulin G; Aspergillus fumigatus; Persistent Infection; Antibodies, Fungal; Chronic Disease
PubMed: 37125929
DOI: 10.1128/spectrum.00264-23 -
Cell Host & Microbe Mar 2023The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning...
The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion.
Topics: Animals; Humans; Aspergillus fumigatus; Phagosomes; Endosomes; Spores, Fungal; Mammals
PubMed: 36893734
DOI: 10.1016/j.chom.2023.02.002 -
Microbes and Infection Sep 2020Platelets are meanwhile recognized as versatile elements within the immune system and appear to play a key role in the innate immune response to pathogens including...
Platelets are meanwhile recognized as versatile elements within the immune system and appear to play a key role in the innate immune response to pathogens including fungi. Previous experiments revealed platelet activation by direct contact with the hyphal-associated polysaccharide galactosaminogalactan (GAG). Since secreted fungal products may also be relevant and trigger immune reactions or thrombosis, we screened culture supernatants (SN) of human-pathogenic fungi for their capacity to activate platelets. For that purpose, platelets were incubated with SN from various fungal species; platelet activation and GAG deposition on the surface of platelets were detected by flow cytometry and electron and confocal microscopy, Culture supernatants of Aspergillus fumigatus and flavus isolates were potent platelet stimulators in a dose- and time-dependent manner, while SN of other Aspergillus species and all tested mucormycete species did not significantly induce platelet activation. The capacity of culture SN to activate platelets was dependent on fungal production of GAG and deposition of secreted GAG on the platelet surface; supernatants from mucormycetes or mutants of A. fumigatus lacking GAG secretion did not affect platelet activity. These results suggest that invading fungi can stimulate platelets not only locally through direct interactions with fungal hyphae, but can also act over a certain distance through secreted GAG.
Topics: Aspergillus; Blood Platelets; Culture Media, Conditioned; Fungal Polysaccharides; Humans; Immunity, Innate; Mucorales; Platelet Activation; Polysaccharides; Species Specificity
PubMed: 31962135
DOI: 10.1016/j.micinf.2019.12.004 -
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 -
Current Opinion in Biotechnology Apr 2020Some of the oldest and most established industrial biotechnology processes involve the fungal production of organic acids. In these fungi, the transport of metabolites... (Review)
Review
Some of the oldest and most established industrial biotechnology processes involve the fungal production of organic acids. In these fungi, the transport of metabolites between cellular compartments, and their secretion, is a major factor. In this review we exemplify the importance of both mitochondrial and plasma membrane transporters in the case of itaconic acid production in two very different fungal systems, Aspergillus and Ustilago. Homologous and heterologous overexpression of both types of transporters, and biochemical analysis of mitochondrial transporter function, show that these two fungi produce the same compound through very different pathways. The way these fungi respond to itaconate stress, especially at low pH, also differs, although this is still an open field which clearly needs additional research.
Topics: Aspergillus; Fungal Proteins; Fungi; Succinates; Ustilago
PubMed: 31689647
DOI: 10.1016/j.copbio.2019.09.014 -
Current Opinion in Microbiology Dec 2020The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen. It is well established that the host utilizes numerous... (Review)
Review
The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen. It is well established that the host utilizes numerous 'patterns of pathogenicity', such as microbial growth, invasion, and viability, to achieve this tuning during bacterial infections. This review discusses how this notion fits during fungal infection, particularly regarding Aspergillus fumigatus infection. Moreover, how the environmental niches filled by A. fumigatus may drive the evolution of the fungal traits responsible for inducing the strain-specific inflammatory responses that have been experimentally observed will be discussed. Moving forward understanding the mechanisms of the fungal strain-specific inflammatory response due to the initial interactions with the host innate immune system will be essential for enhancing our therapeutic options for the treatment of invasive fungal infections.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Fungal Proteins; Humans; Invasive Fungal Infections
PubMed: 32898768
DOI: 10.1016/j.mib.2020.08.004 -
Microbiology Spectrum Dec 2022Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and fungal...
Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and fungal keratitis infections, but closely related species are not considered clinically relevant. To study the evolution of A. flavus pathogenicity, we examined genomic and phenotypic traits of two strains of A. flavus and three closely related species, Aspergillus arachidicola (two strains), Aspergillus parasiticus (two strains), and Aspergillus nomiae (one strain). We identified >3,000 orthologous proteins unique to A. flavus, including seven biosynthetic gene clusters present in A. flavus strains and absent in the three nonpathogens. We characterized secondary metabolite production for all seven strains under two clinically relevant conditions, temperature and salt concentration. Temperature impacted metabolite production in all species, whereas salinity did not affect production of any species. Strains of the same species produced different metabolites. Growth under stress conditions revealed additional heterogeneity within species. Using the invertebrate fungal disease model Galleria mellonella, we found virulence of strains of the same species varied widely; A. flavus strains were not more virulent than strains of the nonpathogens. In a murine model of fungal keratitis, we observed significantly lower disease severity and corneal thickness for A. arachidicola compared to other species at 48 h postinfection, but not at 72 h. Our work identifies variations in key phenotypic, chemical, and genomic attributes between A. flavus and its nonpathogenic relatives and reveals extensive strain heterogeneity in virulence that does not correspond to the currently established clinical relevance of these species. Aspergillus flavus is a filamentous fungus that causes opportunistic human infections, such as aspergillosis and fungal keratitis, but its close relatives are considered nonpathogenic. To begin understanding how this difference in pathogenicity evolved, we characterized variation in infection-relevant genomic, chemical, and phenotypic traits between strains of A. flavus and its relatives. We found extensive variation (or strain heterogeneity) within the pathogenic A. flavus as well as within its close relatives, suggesting that strain-level differences may play a major role in the ability of these fungi to cause disease. Surprisingly, we also found that the virulence of strains from species not considered to be pathogens was similar to that of A. flavus in both invertebrate and murine models of disease. These results contrast with previous studies on Aspergillus fumigatus, another major pathogen in the genus, for which significant differences in infection-relevant chemical and phenotypic traits are observed between closely related pathogenic and nonpathogenic species.
Topics: Humans; Animals; Mice; Aspergillus flavus; Aspergillosis; Aspergillus fumigatus; Genomics; Keratitis
PubMed: 36318036
DOI: 10.1128/spectrum.03069-22