A convergent proline biosynthetic step couples cell wall integrity to virulence in Cryptococcus neoformans.

Pro3, the terminal enzyme of proline biosynthesis in Cryptococcus neoformans, is selectively required for full virulence in a murine infection model, unlike Pro1 and Pro2.

• Why it matters: Proline biosynthesis is important for fungal fitness, but how specific biosynthetic enzymes contribute to pathobiology—especially cell wall integrity and virulence—was unclear.
• What they did: The study characterized Pro1, Pro2, and Pro3 and mapped two converging proline routes to P5C, then tested proline biosynthetic mutants in mice and assessed growth and cell wall integrity.
• The result: While pro1Δ and pro2Δ retained full virulence, pro3Δ showed significantly attenuated virulence with growth defects and impaired cell wall integrity, and partial rescue by altering P5C-generating routes suggests distinct requirements for growth versus cell wall homeostasis.

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