biostudies-literatureUnknownNguyen TVPNIGMS NIH HHSBacteriophage lambda tunes its propensity to lysogenize based on the number of viral genome copies inside the infected cell. Viral self-counting is believed to serve as a way of inferring the abundance of available hosts in the environment. This interpretation is premised on an accurate mapping between the extracellular phage-to-bacteria ratio and the intracellular multiplicity of infection (MOI). However, here we show this premise to be untrue. By simultaneously labeling phage capsids and genomes, we find that, while the number of phages landing on each cell reliably samples the population ratio, the number of phages entering the cell does not. Single-cell infections, followed in a microfluidic device and interpreted using a stochastic model, reveal that the probability and rate of indivibioRxiv : the preprint server for biology2023.06.05.543643https://www.ebi.ac.uk/biostudies/studies/S-EPMC10274716biostudies-literatureCO-INFECTING PHAGES IMPEDE EACH OTHER'S ENTRY INTO THE CELL.PMC10274716R35 GM140709R35 GM144125Chemla YRGolding ITrinh JTZeng LNguyen TVPYao TWu YfalseCO-INFECTING PHAGES IMPEDE EACH OTHER'S ENTRY INTO THE CELL.Bacteriophage lambda tunes its propensity to lysogenize based on the number of viral genome copies inside the infected cell. Viral self-counting is believed to serve as a way of inferring the abundance of available hosts in the environment. This interpretation is premised on an accurate mapping between the extracellular phage-to-bacteria ratio and the intracellular multiplicity of infection (MOI). However, here we show this premise to be untrue. By simultaneously labeling phage capsids and genomes, we find that, while the number of phages landing on each cell reliably samples the population ratio, the number of phages entering the cell does not. Single-cell infections, followed in a microfluidic device and interpreted using a stochastic model, reveal that the probability and rate of indivi2023-01-01T00:00:00Z2023 Jun2025-07-02T03:04:58.22Z2025-07-02T03:04:58.22ZS-EPMC102747163733321710.1101/2023.06.05.543643