Cryptococcal phosphoglucose isomerase is required for virulence factor production, cell wall integrity and stress resistance.
Regulation of virulence factor production in the pathogen Cryptococcus neoformans remains to be fully illustrated. We present here a finding that a gene, encoding the glycolysis enzyme phosphoglucose isomerase (Pgi1), is critical for the biosynthesis of melanin and capsule, cell wall integrity and resistance to stress conditions. A leaky mutant of the yeast, LZM19, resulted from an insertion of T-DNA in the PGI1 promoter region, expressed PGI1 at a level only 1.9% of the wild type. LZM19 could synthesize the pigment melanin in the presence of 2% glucose, suggesting a status of LAC1 derepression. Phenotypically, capsule biosynthesis in LZM19 was remarkably reduced. Integrity of the cell wall and plasma membrane of LZM19 were impaired based on its sensitivity to Congo red and SDS. Also, LZM19 exhibited hypersensitivity to osmotic stress generated by 2 M NaCl or 1 M KCl, indicating possible impairment in the HOG signaling pathway. Furthermore, LZM19 failed to utilize mannose and fructose, suggesting a possible involvement of Pgi1 in the breakdown of these two sugars. Our results revealed a crucial role of PGI1 in coordination of the production of virulence factors, cell wall integrity and stress response in C. neoformans.
National Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Ping
P
Zhang
National Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Dongsheng
D
Wei
National Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Zhongming
Z
Li
National Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Zhixiong
Z
Sun
National Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Jiao
J
Pan
National Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China Institute of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China zhu11187@bnu.edu.cn xudong82@nankai.edu.cn.
Xudong
X
Zhu
D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*; D004251:DNA Transposable Elements; D005632:Fructose / Q000378:metabolism; D015870:Gene Expression; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D016254:Mutagenesis, Insertional; D009997:Osmotic Pressure; D011189:Potassium Chloride / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012965:Sodium Chloride / Q000378:metabolism; D013312:Stress, Physiological; D037521:Virulence Factors / Q000378:metabolism*
D004251:DNA Transposable Elements; D008543:Melanins; D037521:Virulence Factors; D005632:Fructose; D012965:Sodium Chloride; D011189:Potassium Chloride; D005956:Glucose-6-Phosphate Isomerase; D008358:Mannose
Cryptococcus neoformans; HOG pathway; capsule; laccase; melanin; phosphoglucose isomerase