Nitroxoline treatment of Balamuthia mandrillaris triggers genomic crisis, transcriptional collapse, and incomplete encystment via copper and iron chelation.

Nitroxoline treatment of Balamuthia mandrillaris triggers transcriptional collapse and genomic/structural destabilization in encysting cells via copper and iron chelation.

• Why it matters: Granulomatous amebic encephalitis has high mortality and current six-drug therapy has limited efficacy and toxicity, leaving a need for better, mechanistically informed complements.
• What they did: The team generated an annotated draft genome for Balamuthia mandrillaris strain CDC:V039 with long-read sequencing (over 32,000 predicted protein-coding sequences) and used comparative transcriptomics plus chemical complementation, growth assays, and electron microscopy to test encystment under nitroxoline, galactose, and hypoxia.
• The result: Nitroxoline-induced cysts showed transcriptional collapse and genomic and structural destabilization linked to copper and iron chelation, and preformed cysts were also disrupted, supporting continued clinical evaluation as a regimen complement.

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