Fuchs Beth Burgwyn, Tegos George P, Hamblin Michael R, Mylonakis Eleftherios
Infectious Diseases, Massachusetts General Hospital, Boston, MA 02144, USA.
Antimicrob Agents Chemother. 2007 Aug;51(8):2929-36. doi: 10.1128/AAC.00121-07. Epub 2007 Jun 4.
Photodynamic therapy is a rapidly developing antimicrobial technology which combines a nontoxic photoactivatable dye or photosensitizer with harmless visible light of the correct wavelength to excite the dye to its reactive triplet state to generate reactive oxygen species toxic to cells. In this report we present evidence that the fungal pathogen Cryptococcus neoformans is susceptible to photodynamic inactivation by use of a polycationic conjugate of polyethyleneimine and the photosensitizer chlorin(e6). A C. neoformans rom2 mutant, with a mutation involving a putative Rho1 guanyl nucleotide exchange factor that is part of the protein kinase C-cell wall integrity pathway, demonstrated a compromised cell wall and less (1,3)beta-d glucan than the wild-type strain and increased accumulation of PEI-ce6 as assessed by fluorescence uptake and confocal microscopy. Interestingly, C. neoformans rom2 was hypersusceptible to photodynamic inactivation and coincubation of wild-type C. neoformans strain KN99alpha with caspofungin-enhanced photoinactivation. These studies demonstrated that C. neoformans is sensitive to photodynamic therapy and illustrated the significance of cell wall integrity in microbial susceptibility to antimicrobial photodynamic inactivation.
光动力疗法是一种快速发展的抗菌技术，它将无毒的光可激活染料或光敏剂与具有正确波长的无害可见光相结合，使染料激发到其反应性三重态，从而产生活性氧物质，对细胞有毒性。在本报告中，我们提供证据表明，真菌病原体新型隐球菌对使用聚乙烯亚胺和光敏剂二氢卟吩（e6）的聚阳离子共轭物进行光动力灭活敏感。新型隐球菌rom2突变体涉及一种假定的Rho1鸟苷酸交换因子的突变，该因子是蛋白激酶C-细胞壁完整性途径的一部分，与野生型菌株相比，其细胞壁受损，（1,3）β-D-葡聚糖减少，通过荧光摄取和共聚焦显微镜评估，PEI-ce6的积累增加。有趣的是，新型隐球菌rom2对光动力灭活高度敏感，野生型新型隐球菌菌株KN99alpha与卡泊芬净共同孵育可增强光灭活作用。这些研究表明，新型隐球菌对光动力疗法敏感，并说明了细胞壁完整性在微生物对抗菌光动力灭活敏感性中的重要性。
