Temperature-dependent carrier state mediated by H-NS promotes the long-term coexistence of Y. pestis and a phage in soil

Author summaryThe lifestyles of phages beyond the canonical lytic-lysogenic binary are being investigated in the natural environment. The alternative bacteriophage infection strategies mainly include pseudolysogeny and carrier state. Pseudolysogeny stands for a stalled state of development during which the phage genome does not replicate and is asymmetrically transmitted to a daughter cell. This is most often described in conditions of starvation. While the carrier state refers to a stable balance between phages and bacteria at a population level, caused by the persistence of both susceptible and resistant hosts. The ecological consequences of pseudolysogeny and carrier state had been suggested as maintaining both phage and bacteria under unfavorable conditions and promoting horizontal gene transfer. However, the study of the carrier state is very limited due to various technical challenges, including the lack of a stable carrier state model, and the molecular mechanism that maintains a carrier state lifestyle is not well understood. This study demonstrated an H-NS-mediated carrier state lifestyle between a lytic phage and Yersinia pestis, which promotes their coexistence in the soil at a cool temperature. The study of carrier state phages challenged the canonical lytic-lysogenic binary, and carrier state appears to be ubiquitous and ecologically important. However, the mechanisms of the carrier state are not well elucidated due to the limited phage models. Herein, we reported phage HQ103, similar to Escherichia coli phage P2. In contrast to the temperate P2 phage, the HQ103 phage does not insert its genome into the bacterial chromosome and displays a dual behavior depending on the temperature. At 37 & DEG;C, HQ103 lyses the host and forms clear plaques due to the truncation of repressor CI and mutation of promoter Pc. In contrast, HQ103 maintains a carrier state lifestyle with Y. pestis at an environmental temperature (21 & DEG;C). Mechanistically, we found that the host-encoded histone-like nucleoid-structuring protein H-NS, which is highly expressed at 21 & DEG;C to silence the Cox promoter Pe and inhibits the phage lytic cycle. Subsequently, the HQ103 carrier state Y. pestis could grow and co-exist with the phage in the soil at 21 & DEG;C for one month. Thus, this study reveals a novel carrier state lifestyle of phage HQ103 due to the H-NS mediated xenogeneic silencing and demonstrates that the carrier state lifestyle could promote long-term phage-host coexist in nature.