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Permanent Phage Infections

Ziel

The antimicrobial resistance crisis is escalating, and while phage therapy can clear acute infections, eradication of chronic infections reThe antimicrobial resistance crisis is escalating, and while phage therapy can clear acute infections, eradication of chronic infections remains elusive. This limitation is attributed to host physiology under stress that limits phage replication. But the prevailing assumption that virulent phages inevitably proceed to lysis is increasingly challenged. Our recent findings show that nucleus-forming phages can replicate in synchrony with their host across generations without lysis—a phenomenon we summarize as permanent phage replication cycle. This replication strategy is invisible to classical plaque assays, mechanistically unexplored, and may explain why chronic infections resist clearance.

Hypothesis. Nucleus-forming phages use their specialised compartments together with host-takeover factors to establish and maintain permanent replication under stress. If we can define, measure, and disrupt this cycle, we can convert persistence into clearance.

Aims. Define and quantify permanent replication cycles. Map the molecular landscape of permanency. Identify and characterize key determinants, and engineer phages that bypass permanency to generate hyper-virulent phages.

Approach. We combine quantitative virology, utilise time-resolved single-cell assays and fluorescence imaging and electron microscopy in a validated E. coli–Goslarvirus model that demonstrates both technical feasibility and a clear knowledge gap.

Impact. The project will (i) deliver the first mechanistic framework for the permanent phage replication cycle, (ii) establish tools and criteria to detect permanency, guiding the discovery of novel phages, and (iii) provide a rational framework for designing therapeutic phages that skip permanency—enabling faster clearance. This work reframes virulent phage biology and lays the foundation for next-generation phage therapy.

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Finanzierungsplan

HORIZON-ERC - HORIZON ERC Grants

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Aufforderung zur Vorschlagseinreichung

(öffnet in neuem Fenster) ERC-2026-STG

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Gastgebende Einrichtung

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Netto-EU-Beitrag
€ 1 499 982,00
Adresse
INHOFFENSTRASSE 7
38124 Braunschweig
Deutschland
Region
Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt
Aktivitätstyp
Research Organisations
Links
Gesamtkosten
€ 1 499 982,00

Begünstigte (1)