Cryptococcus neoformans is an opportunistic human pathogenic yeast causing life-threatening meningoencephalitis in immunocompromised individuals. We have identified a C. neoformans ALG3 homolog (CnALG3), coding for a dolichyl-phosphate-mannose dependent α -1,3-mannosyltransferase, and constructed a null mutant strain of CnALG3 (Cnalg3Δ). The N-glycan structure analysis, carried by HPLC, exoglycosidase treatment, and MALDI-TOF, showed that Cnalg3Δ generated the truncated N-glycans carrying five mannose residues as a major species. Interestingly, most of the truncated N-glycans of Cnalg3Δ appeared to be devoid of a xylose residue. The glycoproteins produced in Cnalg3Δ, such as phospholipase PLB1, aiding fungal traversal across the blood-brain barrier, and T-cell antigen MP98, were shown to have truncated N-glycans. Cnalg3Δ displayed a moderate defect in capsule biosynthesis and in resistance to oxidative and cell wall stresses, compared to the wild-type (WT) strain. However, noticeably, the Cnalg3Δ mutant strain showed fully attenuated virulence in a mouse model of cryptococcosis, suggesting that the defect in N-glycan assembly affect considerably the pathogenicity of C. neoformans. The attachment to lung epithelial cells and the non-opsonic phagocytosis of Cnalg3Δ were shown to be comparable to those of WT during infection, indicating that the truncated N-linked glycans may not affect the early steps in interaction with host cells. However, the capacity to drive macrophage pyroptosis after phagocytosis was greatly decreased in Cnalg3Δ, indicating a critical role of cryptococcal N-glycans in inducing host cell lysis as a mechanism of host cell escape.
저자
Eun Jung Thak [ Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea ]
Dong-jik Lee [ Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea ]
Seung Yeon Chung [ Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea ]
Hyun Ah Kang [ Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.