Transcriptomic Response of Balamuthia mandrillaris to Lippia graveolens Extract Fractions

Balamuthia mandrillaris is a free-living amoeba pathogenic to humans, causing amoebic granulomatous encephalitis (GAE). Due to the associated mortality rates of <95%, the absence of treatments, and a clear understanding of the pathogenesis of this amoeba, Lippia graveolens could be an interesting alternative since it has been used against bacteria, fungi, and other pathogenic protozoa. This study employed RNA sequencing to analyze differentially expressed genes (DEGs), following treatment with two fractionated L. graveolens extracts (concentration: 150 µg/mL) at 48, 96, and 120 h. The DEGs identified are associated with several functions such as stress responses (Prohibitin domain-containing protein), and oxidative damage repair and cell stability (Peroxiredoxin). Genes implicated in virulence and host interaction also showed significant expression changes, such as the ADP ribosylation factor (Arf) GTPase and ephrin type-A receptor, alongside transcription factors involved in the phagocytosis of amoebas. Additionally, the analysis of Gene Ontology categories revealed terms including transmembrane signaling receptor and protein tyrosine activity, DNA replication initiation, the mitotic M phase, and membrane integrity. These results provide valuable insights into the molecular mechanisms utilized by B. mandrillaris to respond to environmental stressors and the repression of genes related to essential functions, which could serve as potential targets for developing novel strategies.