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Abstract

Nutritional immunity, a key component of the vertebrate innate immune response, involves the modulation of zinc availability to limit the growth of pathogens. counteracts host-imposed zinc starvation through metabolic adaptations, including reprogramming of gene expression and activating efficient metal uptake systems. To unravel how zinc shortage contributes to the complexity of bacterial adaptation to the host environment, it is critical to use model systems that mimic fundamental features of -related diseases in humans. Among available animal models, has recently emerged as a promising alternative to mammalian hosts. This study aims to evaluate whether can recapitulate the zinc-related nutritional immunity responses observed in mammalian infections. Our results show that, upon infection, the larvae upregulate several zinc transporters, suggesting an active redistribution of the metal in response to the pathogen. Additionally, colonizing the larvae induces Zn uptake regulator-controlled genes, consistent with bacterial adaptation to zinc starvation. Disruption of bacterial zinc uptake capability significantly reduces virulence, underscoring the importance of zinc acquisition in pathogenesis also within this model host. As a proof of concept, we also demonstrate that this model can serve as a viable preliminary screening tool to unveil novel players involved in response to zinc starvation, offering valuable insights into the host–pathogen battle for micronutrients.

Funding
This study was supported by the:
  • Rome Technopole (Award Project ECS 0000024)
    • Principal Award Recipient: SecliValerio
  • Rome Technopole (Award Project ECS 0000024)
    • Principal Award Recipient: BattistoniAndrea
  • Italian MUR PRINN 2022 (Award 2022E57Z3K)
    • Principal Award Recipient: BattistoniAndrea
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2025-01-22
2025-11-09

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