Aspergillus Glaucus

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1. Classification

Aspergillus glaucus

a. Higher order taxa

Fungi; Ascomycota; Eurotiomycetes; Eurotiales; Aspergillaceae

2. Description and significance

Aspergillus glaucus is a species of fungus that grows in hyphae, have conidial heads (1) and is characterized by smooth ascospores (2). A fungus with a wide environmental distribution that spans both the Arctic and urban soils, A. glaucus is a pathogen that rarely infects humans because of its high susceptibility to various antifungals (3). Its relative lack of mycotoxin production in many strains lowers the chance for human infections (4). However, as with other members of the Aspergillus genus, A. glaucus is capable of causing infections in immunosuppressed individuals (3). A case of A. glaucus infection is noted in a fatal instance of central nervous system aspergillosis which commonly includes symptoms of mental changes, seizures, and hemiparesis (5).

A. glaucus possesses specialized metabolic capabilities and a novel biosynthetic pathway that produces aspergiolide A, an anthraquinone derivative that is shown to reduce the growth of cancerous cells (6). Aspergiolide A is toxic against several cancerous cell lines including A549 (carcinomic lung cells) and HL60 (leukemia cells) (6). Further research on the pharmacological applications and drug development using aspergiolide A, as well as the efficacy of this secondary metabolite to destroy tumor cells, is conducted (7).

3. Genome structure

Unlike other species of Aspergillus, including A. niger, A. nidulans, A. fumigatus, and A. oryzae, A. glaucus lacks a complete genome sequence. However, genomic characteristics have been studied in relation to other halophilic characteristics and strains of A. glaucus have been shown to contain specific genes that are upregulated while under stress from high salt concentrations (8). Genes that code for the ribosomal protein AgRPS3aE, which is also found in halophilic yeasts, has been studied in relation to A. glaucus’ halophilic capabilities (9). These genes are capable of producing pharmacologically active metabolites, which would prove helpful in future biotechnology and molecular level research. However, these genes are coupled with low frequency of homologous recombination (8). Genome sequencing of A. glaucus may lag behind other species of Aspergillus due to this lack of homologous recombination and nonhomologous end joining pathway. These pathways allow double stranded DNA to be repaired when damaged. Further, without these pathways, targeted gene sequencing and replacement is difficult (8).

4. Cell structure

All Aspergillus species portray growth of yellow perithecia and develop walls that separate the sides of the cell during germination. More specifically, A. glaucus grows in multicellular filaments, or hyphae (2, Figure 1). The individual cells display uniseriate conidial heads that radiate outwards. The conidial heads are often green, blue, reddish, orange, or yellow (1, Figure 2). A. glaucus is characterized by smooth ascospores, typical of fungi classified as ascomycetes, ranging in size from 4.5-10.5 µm (2, Figure 2). These ascospores are a major identifier when differentiating between Aspergillus species.

5. Metabolic processes

Little is known about the metabolic processes specific to A. glaucus, but most Aspergillus species are defined as xerophilic and halophilic (1). Studies of the metabolic processes may be limited for the same reasons as genomic data, in that low frequency of DNA repair pathways makes A. glaucus fragile to work with and study. A. glaucus has been derived from saltern locations, indicating its extremely high NaCl metabolic capabilities (1). Both xerophilic and halophilic characteristics allow the fungus to reproduce in dry environments, specifically ones with extremely low water activity or colder temperatures. Growing in highly saline conditions would infer that A. glaucus uses a protection system to prevent detrimental loss of water through osmotic gradients. One way this is achieved is through synthesis of organic compounds that are stored in the cytoplasm. Metabolic toxicity of A. glaucus is noted and a result of two metabolites that it produces, kotanin and desmethylkotanin (10).

6. Ecology

A. glaucus has worldwide geographic distribution from Arctic marine environments to urban areas to plant materials and soil (1). It is well adapted to environments that are dry, have high sugar concentrations, and have high salt concentrations. It grows optimally at temperatures below 35℃, and is thus used in research focusing on enzymes and cellular structures that function at low temperatures (11). A. glaucus has many applications in the study of pigment formation, human infection, and other enzymes that break down sugars (12). Most importantly, it produces the mycotoxin aspergiolide A which is a potential and powerful anti-tumor compound (7).

7. Pathology

Generally, A. glaucus is not considered to be a very invasive species of fungus and is rarely encountered in clinical laboratories. However, several strains of A. glaucus have been known to produce and release mycotoxins, a class of fungal chemicals that are capable of causing infections. For instance, A. glaucus has been implicated as the cause of ocular infections, especially after traumatic injury to a particular region of the body (5). These ocular infections can range from benign to severe, causing symptoms including ocular discharge, visual impairment, or red and painful eyes. Treatment for ocular infections can also range from mild to aggressive, depending on the severity of the infection and what part of the eye is infected (13). There have also been other types of infections associated with A. glaucus including cerebral, orofacial, cardiovascular, pulmonary, nasal and ear infections, although these are rare. There has only been one recorded instance of an infection caused by A. glaucus that resulted in a fatality. An otherwise healthy and immunocompetent adult contracted a brain infection caused by A. glaucus, which ultimately led to his death despite aggressive antifungal treatments (5).

8. Current Research

Current A. glaucus research involves the continuing effort to further understand the mycotoxin aspergiolide A that has potential benefit in cancer study (6). The biosynthetic pathway of aspergiolide A production has been determined (7). Further, novel methods of enhancing the production of the antitumor compound, along with other compounds with potential human health benefit, have been developed (14, 15). Along with developing aspergiolide A production methods, the effects that this mycotoxin has on the growth and sexual development of the fungus itself are also being explored in an attempt to better understand fungal physiology (16). Recent studies have focused on the enzyme b-1,4-glucosidase, and other enzymes like it produced by A. glaucus, to break down polysaccharides and starches (17, 18). Another recent study tested A. glaucus resistance to abiotic environmental conditions and explored the function of the ribosomal protein RPL44 which conferred such resistances (19). To better understand the genome of A. glaucus, improvements have been made in gene targeting procedures and sequencing methods as well (8).

9. References

This page was produced by Andrew Lacqua, Julia Tom, Linda Wong, and Greg Dilliberto of Boston University (1) Hubka, V., M. Kolarik, A. Kubátová, and S. Peterson. 2013. Taxonomic revision of Eurotium and transfer of species to Aspergillus. Mycologia 105: 912–37. (2) Thom, C., & Raper, K. B. (1941). The Aspergillus glaucus group (Vol. 424). US Dept. of Agriculture. (3) Araujo, R., C. Pina-Vaz, and A.G. Rodrigues. 2007. Susceptibility of environmental versus clinical strains of pathogenic Aspergillus. International Journal of Antimicrobial Agents 29: 108-111. (4) Bachmann, M., J. Luethy, and C. Schlatter. 1979. Toxicity and mutagenicity of molds of the Aspergillus Glaucus group: identification of physcion and three related anthraquinones as main toxic constituents from Aspergillus Chevalieri. Journal of Agricultural and Food Chemistry 27: 1342-347. (5) Traboulsi, R.S., M.M. Kattar, O. Dbouni, G.F. Araj, S.S. Kanj. 2007. Fatal brain infection caused by Aspergillus Glaucus in an immunocompetent patient identified by sequencing of the ribosomal 18S-28S internal transcribed spacer. European Journal of Clinical Microbiology and Infectious Diseases 26: 747-750. (6) Tao, K., L. Du, X. Sun, M. Cai, T. Zhu, X. Zhou, Q. Gu, and Y. Zhang. 2009. Biosynthesis of aspergiolide A, a novel antitumor compound by a marine-derived fungus Aspergillus Glaucus via the polyketide pathway. Tetrahedron 50: 1082-1085. (7) Sun, X., X. Zhou, M. Cai, K. Tao, and Y. Zhang. 2006. Identified biosynthetic pathway of aspergiolide a and a novel strategy to increase its production in a marine-derived fungus Aspergillus Glaucus by feeding of biosynthetic precursors and inhibitors simultaneously. Bioresource Technology 100: 4244-251. (8) Fang, Z., Y. Zhang, M. Cai, J. Zhang, Y. Zhang, and X. Zhou. 2012. Improved Gene Targeting Frequency in Marine-derived Filamentous Fungus Aspergillus Glaucus by Disrupting LigD. Journal of Applied Genetics 53: 355-62. (9) Liang, X., Liu, Y., Xie, L., Liu, X., Wei, Y., Zhou, X., & Zhang, S. (2015). A Ribosomal Protein AgRPS3aE from Halophilic Aspergillus glaucus Confers Salt Tolerance in Heterologous Organisms. International journal of molecular sciences, 16(2), 3058-3070. (10) Du, L., T. Zhu, Y. Fang, H. Liu, Q. Gu, and W. Zhu. 2007. Aspergiolide A (I), a novel anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton isolated from a marine-derived fungus Aspergillus Glaucus. Tetrahedron 63: 1085-1088. (11) Abellana, M., J. Benedi, V. Sanchis, and A. J. Ramos. 1999. Water Activity and Temperature Effects on Germination and Growth of Eurotium Amstelodami, E. Chevalieri and E. Herbariorum Isolates from Bakery Products. Journal of Applied Microbiology 87: 371-80. (12) Nordberg H., M. Cantor, S. Dusheyko, S. Hua, A. Poliakov, I. Shabalov, T. Smirnova, IV. Grigoriev, and I. Dubchak. 2014. The Genome Portal of the Department of Energy Joint Genome Institute. Nucleic Acids Res. 42:26-31. (13) Donahue, S., J. Khoury, R. Kowalski. 1996. Common Ocular Infections. A Prescriber’s Guide. Drugs 52: 526-540. (14) Cai, M., X. Zhou, J. Lu, W. Fan, C. Niu, J. Zhou, X. Sun, L. Kang, and Y. Zhang. 2011. Enhancing Aspergiolide A Production from a Shear-sensitive and Easy-foaming Marine-derived Filamentous Fungus Aspergillus Glaucus by Oxygen Carrier Addition and Impeller Combination in a Bioreactor. Bioresource Technology 102: 3584-586. (15) Cai, M., X. Zhou, J. Lu, W. Fan, J. Zhou, C. Niu, L. Kang, X. Sun, and Y. Zhang. 2012. An Integrated Control Strategy for the Fermentation of the Marine-Derived Fungus Aspergillus Glaucus for the Production of Anti-cancer Polyketide. Marine Biotechnology Mar Biotechnol 14: 665-71. (16) Cai, M., X. Zhou, J. Zhou, C. Niu, L. Kang, X. Sun, and Y. Zhang. 2010. Efficient Strategy for Enhancing Aspergiolide A Production by Citrate Feedings and Its Effects on Sexual Development and Growth of Marine-derived Fungus Aspergillus Glaucus. Bioresource Technology 101: 6059-068. (17) Tao, Y., X. Zhu, J. Huang, S. Ma, X. Wu, M. Long, and Q. Chen. 2010. Purification and Properties of Endoglucanase from a Sugar Cane Bagasse Hydrolyzing Strain, Aspergillus Glaucus. Journal of Agricultural and Food Chemistry 58: 6126-130. (18) Ma, S., B. Long, X. Xu, X. Zhou, Y. She, Y. Tao, S. Chen, M. Long, and Q. Chen. 2014. Purification and Characterization of B-1,4-glucosidase from Aspergillus Glaucus. African Journal of Biotechnology 10: 19607-9614. (19) Liu, X., L. Xie, Y. Wei, X. Zhou, B. Jia, J. Liu, and S. Zhang. 2014. Abiotic Stress Resistance, a Novel Moonlighting Function of Ribosomal Protein RPL44 in the Halophilic Fungus Aspergillus Glaucus. Applied and Environmental Microbiology 80: 4294-300.

Edited by students of Jennifer Talbot for BI 311 General Microbiology, 2015, Boston University.