A novel bacteriophage nucleoid-associated protein that disrupts bacterial chromosome segregation

Bacterial nucleoid-associated proteins, such as Fis and IHF, influence multiple DNA transactions including global transcriptional regulation and genome organization. Here we report the identification and characterization of a bacteriophage ?-encoded nucleoid-associated protein, NinH, which is structurally and functionally related to Escherichia coli Fis. Purified NinH binds double-stranded DNA in vitro and introduces a pronounced bend similar to that imposed by Fis. Fluorescence microscopy was used to validate a direct interaction between NinH and the bacterial nucleoid in vivo. NinH overexpression in E. coli wild-type cells severely impairs growth and disrupts nucleoid segregation, resulting in a doubling of cell length. In contrast, low-level expression of NinH confers no detrimental effects upon wild-type E. coli but does result in the differential expression of a small subset of bacterial genes, notably conferring increased sensitivity to acid conditions. Trace levels of NinH, however, do significantly impair growth and trigger cell elongation in strains defective in certain nucleoid-associated proteins, mirroring the effects seen with high-level expression of NinH in the wild-type. Our study reveals that phage ? has co-opted a bacterial architectural protein to manipulate host gene expression patterns and perturb normal nucleoid segregation, ultimately creating the opportunity to increase cell volume and maximize progeny yield.