Trichosporon asahii PLA2 Gene Enhances Drug Resistance to Azoles by Improving Drug Efflux and Biofilm Formation

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8855
• Main Authors: Ma, Xiaoping, Liu, Hong, Liu, Zhen, Wang, Ya, Zhong, Zhijun, Peng, Guangneng, Gu, Yu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.05.2023; MDPI
• Subjects: Amino acids; Antifungal agents; Antifungal Agents - pharmacology; Arthrospores; Azoles; Azoles - pharmacology; Biodegradation; Biofilms; cell wall; Cell walls; Chitin; Drug resistance; Drug Resistance, Fungal - genetics; Efflux; Fungi; Fungicides; Gene expression; Genes; Genomes; Heterocyclic compounds; Homologous recombination; Humans; Immune response; Lipids; MAP kinase; Metabolism; Metabolites; Morphology; Opportunist infection; overexpression; Phospholipase A2; Polymerase chain reaction; Protein structure; Proteins; Signal transduction; Sodium dodecyl sulfate; TaPLA2; Trichosporon - genetics; Trichosporon asahii; TaPLA2; drug-resistance; Trichosporon asahii; overexpression; cell wall
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108855

is an opportunistic pathogen that can cause severe or even fatal infections in patients with low immune function. plays different roles in different fungi and is also related to fungal drug resistance. However, the mechanism underlying its drug resistance to azoles has not yet been reported in . Therefore, we investigated the drug resistance of ( ) by constructing overexpressing mutant strains (TaPLA2 ). TaPLA2 was generated by homologous recombination of the recombinant vector pEGFP-N1-TaPLA2, induced by the CMV promoter, with . The structure of the protein was found to be typical of sPLA2, and it belongs to the phospholipase A2_3 superfamily. TaPLA2 enhanced antifungal drug resistance by upregulating the expression of effector genes and increasing the number of arthrospores to promote biofilm formation. TaPLA2 was highly sensitive to sodium dodecyl sulfate and Congo red, indicating impaired cell wall integrity due to downregulation of chitin synthesis or degradation genes, which can indirectly affect fungal resistance. In conclusion, overexpression enhanced the resistance to azoles of by enhancing drug efflux and biofilm formation and upregulating HOG-MAPK pathway genes; therefore, it has promising research prospects.