Cryptic-Prophage-Encoded Small Protein DicB Protects Escherichia coli from Phage Infection by Inhibiting Inner Membrane Receptor Proteins

Abstract

Bacterial genomes harbor cryptic prophages that have lost genes required for induction, excision from host chromosomes, or production of phage progeny. Escherichia coli K-12 strains contain a cryptic prophage, Qin, that encodes a small RNA, DicF, and a small protein, DicB, that have been implicated in control of bacterial metabolism and cell division. Since DicB and DicF are encoded in the Qin immunity region, we tested whether these gene products could protect the E. coli host from bacteriophage infection. Transient expression of the dicBF operon yielded cells that were ∼100-fold more resistant to infection by λ phage than control cells, and the phenotype was DicB dependent. DicB specifically inhibited infection by λ and other phages that use ManYZ membrane proteins for cytoplasmic entry of phage DNA. In addition to blocking ManYZ-dependent phage infection, DicB also inhibited the canonical sugar transport activity of ManYZ. Previous studies demonstrated that DicB interacts with MinC, an FtsZ polymerization inhibitor, causing MinC localization to midcell and preventing Z ring formation and cell division. In strains producing mutant MinC proteins that do not interact with DicB, both DicB-dependent phenotypes involving ManYZ were lost. These results suggest that DicB is a pleiotropic regulator of bacterial physiology and cell division and that these effects are mediated by a key molecular interaction with the cell division protein MinC.IMPORTANCE Temperate bacteriophages can integrate their genomes into the bacterial host chromosome and exist as prophages whose gene products play key roles in bacterial fitness and interactions with eukaryotic host organisms. Most bacterial chromosomes contain "cryptic" prophages that have lost genes required for production of phage progeny but retain genes of unknown function that may be important for regulating bacterial host physiology. This study provides such an example, where a cryptic-prophage-encoded product can perform multiple roles in the bacterial host and influence processes, including metabolism, cell division, and susceptibility to phage infection. Further functional characterization of cryptic-prophage-encoded functions will shed new light on host-phage interactions and their cellular physiological implications.

Keywords: Hfq; cell division; prophages; small RNA; small protein; sugars.