Persistent lytic bacteriophage infection as a novel strategy for exploitation of nutrient-limited host bacteria

Wild bacteria, from the open ocean to the gut, experience persistent nutrient limitation. This fundamentally affects bacterial physiology and metabolism and has profound impacts on their infection by bacterial viruses (bacteriophages). For virulent bacteriophages, which cannot enter a lysogenic state, this poses a problem for environmental persistence. Here we demonstrate that virulent bacteriophage SPP1 productively infects nutrient-limited stationary phase cultures of the Gram-positive bacterium Bacillus subtilis. Slow production and release of low numbers of infective viral particles resulted from a prolonged infection of the host population. Extensive culture lysis was greatly delayed, releasing additional viral particles and promoting fresh infections of bacterial survivors. Induced overproduction of cell surface bacteriophage receptor YueB, compensating for its scarcity in stationary phase, expedited infection dynamics under nutrient-limiting conditions, but did not change overall infection productivity. The temporal program of SPP1 gene expression differed from exponential phase, consistent with a prolonged, persistent mode of infection. Reduced expression of genes coding viral structural proteins correlated with the low yield of infectious particles. Importantly, exogenous influx of the carbon source maltose enhanced viral particle production. Our results uncover a novel adaptive strategy of a lytic phage for productive infection of nutrient-limited bacterial populations through persistent, exhaustive infection. ### Competing Interest Statement The authors have declared no competing interest.