title: Possible participation of the Rho/Rho-associated coiled-coil-forming kinase pathway in the cell death of Cryptococcus neoformans caused by Staphylococcus aureus adherence.
abstract: We here report the apoptotic death of a fungus, Cryptococcus neoformans (C. neoformans), in response to adherence of the pathogenic bacterium Staphylococcus aureus (S. aureus). In co-culture, cryptococcal actin was visibly aggregated. To investigate the mechanism of death, the participation of small GTP(guanosine triphosphate)-binding proteins belonging to the Rho subfamily, which regulate the actin cytoskeleton, was explored. C. neoformans was cultured with S. aureus in the presence of N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide (Y-27632), an inhibitor of Rho-associated coiled-coil forming kinase (ROCK), a downstream effector of Rho. Death of C. neoformans was significantly reduced by the inhibitor. Concomitantly, Y-27632 prevented the aggregation of actin. Therefore, it was concluded that the Rho/ROCK pathway is involved in cell death induced by adherence stress. Increased expression of the voltage-dependent anion channel (VDAC), located in the mitochondrial outer membrane, has previously been observed in the apoptosis-like death of C. neoformans in the presence of hydrogen peroxide. Ruthenium red (RuR), which binds to VDAC and inhibits cytochrome c release, was used to determine the involvement of VDAC following adherence stress caused by S. aureus. RuR treatment increased the viability of C. neoformans co-cultured with S. aureus in a dose dependent manner. These findings suggest that Rho-ROCK signaling could be involved, via a mitochondrial pathway, in the apoptosis-like death of C. neoformans induced by the adherence of S. aureus.
authors.affiliation: Department of Microbiology, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. ikeda@my-pharm.ac.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikeda
mesh_terms: D000199:Actins / Q000378:metabolism; D017209:Apoptosis; D001422:Bacterial Adhesion; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000502:physiology*; D011489:Protein Denaturation; D055503:Protein Multimerization; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins