title: Identification of Naegleria fowleri proteins linked to primary amoebic meningoencephalitis.
abstract: Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis, a rapidly fatal disease of the central nervous system. N. fowleri can exist in cyst, flagellate or amoebic forms, depending on environmental conditions. The amoebic form can invade the brain following introduction into the nasal passages. When applied intranasally to a mouse model, cultured N. fowleri amoebae exhibit low virulence. However, upon serial passage in mouse brain, the amoebae acquire a highly virulent state. In the present study, a proteomics approach was applied to the identification of N. fowleri amoeba proteins whose expression was associated with the highly virulent state in mice. Mice were inoculated intranasally with axenically cultured amoebae or with mouse-passaged amoebae. Examination by light and electron microscopy revealed no morphological differences. However, mouse-passaged amoebae were more virulent in mice as indicated by exhibiting a two log10 titre decrease in median infective dose 50 (ID50). Scatter plot analysis of amoebic lysates revealed a subset of proteins, the expression of which was associated with highly virulent amoebae. MS-MS indicated that this subset contained proteins that shared homology with those linked to cytoskeletal rearrangement and the invasion process. Invasion assays were performed in the presence of a select inhibitor to expand on the findings. The collective results suggest that N. fowleri gene products linked to cytoskeletal rearrangement and invasion may be candidate targets in the management of primary amoebic meningoencephalitis.
authors.affiliation: Department of Clinical Laboratory Sciences, Virginia Commonwealth University School of Allied Health Professions, Richmond, VA 23298-0583, USA.|Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0678, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Jamerson
authors.affiliation: Department of Clinical Laboratory Sciences, Virginia Commonwealth University School of Allied Health Professions, Richmond, VA 23298-0583, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Schmoyer
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0678, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0678, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Marciano-Cabral
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0678, USA.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Cabral
mesh_terms: D000562:Amebiasis / Q000469:parasitology / Q000473:pathology*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D020808:Central Nervous System Protozoal Infections / Q000469:parasitology / Q000473:pathology*; D004195:Disease Models, Animal; D008590:Meningoencephalitis / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D016848:Naegleria fowleri / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014774:Virulence
chemical_list: D015800:Protozoan Proteins