Publication Date
2021
Journal or Book Title
BMC Biology
Abstract
The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. Results Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. Conclusions In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.
ORCID
Ramirez-Macias, Inmaculada/0000-0001-9559-9180; van der Giezen, Mark/0000-0002-1033-1335
DOI
https://doi.org/10.1186/s12915-021-01078-1
Volume
19
Issue
1
License
UMass Amherst Open Access Policy
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Funder
AHFMR Fulltime Graduate Studentship; Vanier Canada Graduate Scholarship; Canada Research Chair in Evolutionary Cell Biology; CePaViP [CZ.02.1.01/0.0/0.0/16_019/0000759]; Czech Science FoundationGrant Agency of the Czech Republic [18-18699S]; CSIRO Land; Water (Australia)
Recommended Citation
Herman, Emily K.; Greninger, Alex; van der Giezen, Mark; Ginger, Michael L.; Ramirez-Macias, Immaculada; Miller, Haylea C.; Morgan, Matthew J.; Tsaousis, Anastasios D.; Velle, Katrina; and Vargová, Romana, "Genomics and Transcriptomics Yields a System-Level View of the Biology of the Pathogen Naegleria Fowleri" (2021). BMC Biology. 653.
https://doi.org/10.1186/s12915-021-01078-1