The Past, Present, and Future of Genetic Manipulation in Human Fungal Pathogen Talaromyces marneffei
DOI:
https://doi.org/10.33165/rmj.2024.47.1.266695Keywords:
Genetics manipulation, Talaromycosis, Talaromyces marneffei, CRISPRAbstract
The fungus Talaromyces marneffei has been discovered and its pathogenicity to humans has been recognized for over 60 years. The advances in organism-wide studies and the development of genetic manipulation tools contribute greatly to our current understanding of host-pathogen interactions. Several classes of genes have been identified to be involved in stress response, morphogenesis, and virulence based on the characterization of the generated mutants. Here, we summarize the main techniques for T. marneffei genetic manipulation, including chemical mutagenesis, insertional mutagenesis, homologous recombination-mediated gene replacement, knockdown methods, and the recent popular clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) technology. The advantages and disadvantages of each technique were determined from a historical perspective. We also describe potential strategies to improve the current genetics studies, such as the generation of new selection markers and genetically modified strains. Our review has demonstrated that Thailand will continue to make efforts to become a leader in T. marneffei genetics research. The genetic approaches have impacted the studies of T. marneffei and can lead to the discovery of new diagnostic tools, drugs, and vaccines.
References
Segretain G. Description d’une nouvelle espece de Penicillium: Penicillium marneffei n. sp. Bull Soc Mycol Fr. 1959;75:412-416.
Supparatpinyo K, Khamwan C, Baosoung V, Nelson KE, Sirisanthana T. Disseminated Penicillium marneffei infection in southeast Asia. Lancet. 1994;344(8915):110-113. doi:10.1016/s0140-6736(94)91287-4
Garrison RG, Boyd KS. Dimorphism of Penicillium marneffei as observed by electron microscopy. Can J Microbiol. 1973;19(10):1305-1309. doi:10.1139/m73-209
Vanittanakom N, Cooper CR Jr, Fisher MC, Sirisanthana T. Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev. 2006;19(1):95-110. doi:10.1128/CMR.19.1.95-110.2006
Narayanasamy S, Dat VQ, Thanh NT, et al. A global call for talaromycosis to be recognised as a neglected tropical disease. Lancet Glob Health. 2021;9(11):e1618-e1622. doi:10.1016/S2214-109X(21)00350-8
Wang F, Han R, Chen S. An overlooked and underrated endemic mycosis-talaromycosis and the pathogenic fungus Talaromyces marneffei. Clin Microbiol Rev. 2023;36(1):e0005122. doi:10.1128/cmr.00051-22
Supparatpinyo K, Sirisanthana T. Disseminated Penicillium marneffei infection diagnosed on examination of a peripheral blood smear of a patient with human immunodeficiency virus infection. Clin Infect Dis. 1994;18(2):246-247. doi:10.1093/clinids/18.2.246
Rodrigues ML, Nosanchuk JD. Recognition of fungal priority pathogens: What next? PLoS Negl Trop Dis. 2023;17(3):e0011136. doi:10.1371/journal.pntd.0011136
Boyce KJ, Bugeja HE, Weerasinghe H, Payne MJ, Schreider L. Strategies for the molecular genetic manipulation and visualization of the human fungal pathogen Penicillium marneffei. Fungal Genetics Reports. 2012;59(1):1-12. doi:10.4148/1941-4765.1009
Pronk JT. Auxotrophic yeast strains in fundamental and applied research. Appl Environ Microbiol. 2002;68(5):2095-2100. doi:10.1128/AEM.68.5.2095-2100.2002
Bugeja HE, Boyce KJ, Weerasinghe H, et al. Tools for high efficiency genetic manipulation of the human pathogen Penicillium marneffei. Fungal Genet Biol. 2012;49(10):772-778. doi:10.1016/j.fgb.2012.08.003
Kummasook A, Cooper CR Jr, Sakamoto A, Terui Y, Kashiwagi K, Vanittanakom N. Spermidine is required for morphogenesis in the human pathogenic fungus, Penicillium marneffei. Fungal Genet Biol. 2013;58-59:25-32. doi:10.1016/j.fgb.2013.08.001
Nimmanee P, Woo PC, Vanittanakom P, Youngchim S, Vanittanakom N. Functional analysis of atfA gene to stress response in pathogenic thermal dimorphic fungus Penicillium marneffei. PLoS One. 2014;9(11):e111200. doi:10.1371/journal.pone.0111200
Kummasook A, Cooper CR Jr, Vanittanakom N. An improved Agrobacterium-mediated transformation system for the functional genetic analysis of Penicillium marneffei. Med Mycol. 2010;48(8):1066-1074. doi:10.3109/13693781003801219
Woo PC, Lau SK, Lau CC, et al. Mp1p is a virulence factor in Talaromyces (Penicillium) marneffei. PLoS Negl Trop Dis. 2016;10(8):e0004907. doi:10.1371/journal.pntd.0004907
Jin FJ, Maruyama J, Juvvadi PR, Arioka M, Kitamoto K. Adenine auxotrophic mutants of Aspergillus oryzae: development of a novel transformation system with triple auxotrophic hosts. Biosci Biotechnol Biochem. 2004;68(3):656-662. doi:10.1271/bbb.68.656
Fisher CR. Enzymology of the pigmented adenine-requiring mutants of Saccharomyces and Schizosaccharomyces. Biochem Biophys Res Commun. 1969;34(3):306-310. doi:10.1016/0006-291x(69)90832-8
Wangsanut T, Sukantamala P, Pongpom M. Identification of glutathione metabolic genes from a dimorphic fungus Talaromyces marneffei and their gene expression patterns under different environmental conditions. Sci Rep. 2023;13(1):13888. doi:10.1038/s41598-023-40932-w
Weerasinghe H, Payne M, Beard S, Andrianopoulos A. Organism-wide studies into pathogenicity and morphogenesis in Talaromyces marneffei. Future Microbiol. 2016;11(4):511-526. doi:10.2217/fmb.16.9
Borneman AR, Hynes MJ, Andrianopoulos A. An STE12 homolog from the asexual, dimorphic fungus Penicillium marneffei complements the defect in sexual development of an Aspergillus nidulans steA mutant. Genetics. 2001;157(3):1003-1014. doi:10.1093/genetics/157.3.1003
Zhang P, Xu B, Wang Y, et al. Agrobacterium tumefaciens-mediated transformation as a tool for insertionalmutagenesis in the fungus Penicillium marneffei. Mycol Res. 2008;112(Pt 8):943-949. doi:10.1016/j.mycres.2008.01.017
Xiao X, Feng J, Li Y, et al. Agrobacterium tumefaciens-mediated transformation: an efficient tool for targeted gene disruption in Talaromyces marneffei. World J Microbiol Biotechnol. 2017;33(10):183. doi:10.1007/s11274-017-2352-0
Woo PC, Zhen H, Cai JJ, et al. The mitochondrial genome of the thermal dimorphic fungus Penicillium marneffei is more closely related to those of molds than yeasts. FEBS Lett. 2003;555(3):469-477. doi:10.1016/s0014-5793(03)01307-3
Woo PC, Lau SK, Liu B, et al. Draft genome sequence of Penicillium marneffei strain PM1. Eukaryot Cell. 2011;10(12):1740-1741. doi:10.1128/EC.05255-11
Nierman WC, Fedorova-Abrams ND, Andrianopoulos A. Genome sequence of the AIDS-associated pathogen Penicillium marneffei (ATCC18224) and its near taxonomic relative Talaromyces stipitatus (ATCC10500). Genome Announc. 2015;3(1):e01559-14. doi:10.1128/genomeA.01559-14
Borneman AR, Hynes MJ, Andrianopoulos A. The abaA homologue of Penicillium marneffei participates in two developmental programmes: conidiation and dimorphic growth. Mol Microbiol. 2000;38(5):1034-1047. doi:10.1046/j.1365-2958.2000.02202.x
Woo PC, Tam EW, Chong KT, et al. High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei. FEBS J. 2010;277(18):3750-3758. doi:10.1111/j.1742-4658.2010.07776.x
Woo PC, Lam CW, Tam EW, et al. First discovery of two polyketide synthase genes for mitorubrinic acid and mitorubrinol yellow pigment biosynthesis and implications in virulence of Penicillium marneffei. PLoS Negl Trop Dis. 2012;6(10):e1871. doi:10.1371/journal.pntd.0001871
Zadra I, Abt B, Parson W, Haas H. xylP promoter-based expression system and its use for antisense downregulation of the Penicillium chrysogenum nitrogen regulator NRE. Appl Environ Microbiol. 2000;66(11):4810-4816. doi:10.1128/AEM.66.11.4810-4816.2000
Pongsunk S, Andrianopoulos A, Chaiyaroj SC. Conditional lethal disruption of TATA-binding protein gene in Penicillium marneffei. Fungal Genet Biol. 2005;42(11):893-903. doi:10.1016/j.fgb.2005.07.002
Weerasinghe H, Bugeja HE, Andrianopoulos A. The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells. Sci Rep. 2021;11(1):2334. doi:10.1038/s41598-020-79593-4
Qiao YM, Yu RL, Zhu P. Advances in targeting and heterologous expression of genes involved in the synthesis of fungal secondary metabolites. RSC Adv. 2019;9(60):35124-35134. doi:10.1039/c9ra06908a
Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014;32(4):347-355. doi:10.1038/nbt.2842
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-821. doi:10.1126/science.1225829
Hwang WY, Fu Y, Reyon D, et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013;31(3):227-229. doi:10.1038/nbt.2501
Cong L, Ran FA, Cox D, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819-823. doi:10.1126/science.1231143
Mali P, Yang L, Esvelt KM, et al. RNA-guided human genome engineering via Cas9. Science. 2013;339(6121):823-826. doi:10.1126/science.1232033
Zhang X, Hu X, Jan S, et al. Development of CRISPR-Cas9 genome editing system in Talaromyces marneffei. Microb Pathog. 2021;154:104822. doi:10.1016/j.micpath.2021.104822
Vanegas KG, Jarczynska ZD, Strucko T, Mortensen UH. Cpf1 enables fast and efficient genome editing in Aspergilli. Fungal Biol Biotechnol. 2019;6:6. doi:10.1186/s40694-019-0069-6
Shapiro RS, Chavez A, Porter CBM, et al. A CRISPR-Cas9-based gene drive platform for genetic interaction analysis in Candida albicans. Nat Microbiol. 2018;3(1):73-82. doi:10.1038/s41564-017-0043-0
Song R, Zhai Q, Sun L, et al. CRISPR/Cas9 genome editing technology in filamentous fungi: progress and perspective. Appl Microbiol Biotechnol. 2019;103(17):6919-6932. doi:10.1007/s00253-019-10007-w
Li Q, Lu J, Zhang G, et al. CRISPR/Cas9-mediated multiplexed genome editing in Aspergillusoryzae. J Fungi (Basel). 2023;9(1):109. doi:10.3390/jof9010109
Shalem O, Sanjana NE, Zhang F. High-throughput functional genomics using CRISPR-Cas9. Nat Rev Genet. 2015;16(5):299-311. doi:10.1038/nrg3899
Amsri A, Srichairatanakool S, Teerawutgulrag A, Youngchim S, Pongpom M. Genetic engineering of Talaromyces marneffei to enhance siderophore production and preliminary testing for medical application potential. J Fungi (Basel). 2022;8(11):1183. doi:10.3390/jof8111183
Sze KH, Lam WH, Zhang H, et al. Talaromyces marneffei Mp1p is a virulence factor that binds and sequesters a key proinflammatory lipid to dampen host innate immune response. Cell Chem Biol. 2017;24(2):182-194. doi:10.1016/j.chembiol.2016.12.014
Ly VT, Thanh NT, Thu NTM, et al. Occult Talaromyces marneffei infection unveiled by the novel Mp1p antigen detection assay. Open Forum Infect Dis. 2020;7(11):ofaa502. doi:10.1093/ofid/ofaa502
Chen X, Ou X, Wang H, et al. Talaromyces marneffei Mp1p antigen detection may play an important role in the early diagnosis of talaromycosis in patients with acquired immunodeficiency syndrome. Mycopathologia. 2022;187(2-3):205-215. doi:10.1007/s11046-022-00618-9
Yang F, Yuen K-Y, Lau SK, Woo PC. Vaccine mediates protection against penicilliosis in BALB/c mice (MPF2P.810). J Immunol. 2014;192(1Suppl):67.9. doi:10.4049/jimmunol.192.Supp.67.9
Pongpom P, Cooper CR Jr, Vanittanakom N. Isolation and characterization of a catalase-peroxidase gene from the pathogenic fungus, Penicillium marneffei. Med Mycol. 2005;43(5):403-411. doi:10.1080/13693780400007144
Suwunnakorn S, Cooper CR, Kummasook A, Vanittanakom N. Role of the yakA gene in morphogenesis and stress response in Penicillium marneffei. Microbiology. 2014;160(Pt 9):1929-1939. doi:10.1099/mic.0.080689-0
Nimmanee P, Woo PC, Kummasook A, Vanittanakom N. Characterization of sakA gene from pathogenic dimorphic fungus Penicillium marneffei. Int J Med Microbiol. 2015;305(1):65-74. doi:10.1016/j.ijmm.2014.11.003
Suwunnakorn S, Cooper CR Jr, Kummasook A, Pongpom M, Vanittanakom P, Vanittanakom N. Role of the rttA gene in morphogenesis, stress response, and virulence in the human pathogenic fungus Penicillium marneffei. Med Mycol. 2015;53(2):119-131. doi:10.1093/mmy/myu063
Sapmak A, Boyce KJ, Andrianopoulos A, Vanittanakom N. The pbrB gene encodes a laccase required for DHN-melanin synthesis in conidia of Talaromyces (Penicillium) marneffei. PLoS One. 2015;10(4):e0122728. doi:10.1371/journal.pone.0122728
Dankai W, Pongpom M, Youngchim S, Cooper CR Jr, Vanittanakom N. The yapA encodes bZIP transcription factor involved in stress tolerance in pathogenic fungus Talaromyces marneffei. PLoS One. 2016;11(10):e0163778. doi:10.1371/journal.pone.0163778
Pongpom M, Sawatdeechaikul P, Vanittanakom N. An antigenic protein Mplp6 is dispensable in Talaromyces marneffei. Acta Scientific Microbiology. 2018;1(3):14-21. doi:10.31080/ASMI.2018.01.0022
Amsri A, Jeenkeawpieam J, Sukantamala P, Pongpom M. Role of acuK in control of iron acquisition and gluconeogenesis in Talaromyces marneffei. J Fungi (Basel). 2021;7(10):798. doi:10.3390/jof7100798
Wangsanut T, Amsri A, Pongpom M. Antibody screening reveals antigenic proteins involved in Talaromyces marneffei and human interaction. Front Cell Infect Microbiol. 2023;13:1118979. doi:10.3389/fcimb.2023.1118979
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Ramathibodi Medical Journal
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.