Not a barrier but a key: How bacteriophages exploit host's O-antigen as an essential receptor to initiate infection

Tailed bacteriophages specific for Gram-negative bacteria encounter lipopolysaccharide (LPS) during the first infection steps. Yet, it is not well understood how biochemistry of these initial interactions relates to subsequent events that orchestrate phage adsorption and tail rearrangements to initiate cell entry. For many phages, long O-antigen chains found on the LPS of smooth bacterial strains serve as essential receptor recognized by their tailspike proteins (TSP). Many TSP are depolymerases and O-antigen cleavage was described as necessary step for subsequent orientation towards a secondary receptor. However, O-antigen specific host attachment must not always come along with O-antigen degradation. In this issue of Molecular Microbiology Prokhorov et al. report that coliphage G7C carries a TSP that deacetylates O-antigen but does not degrade it, whereas rough strains or strains lacking O-antigen acetylation remain unaffected. Bacteriophage G7C specifically functionalizes its tail by attaching the deacetylase TSP directly to a second TSP that is nonfunctional on the host's O-antigen. This challenges the view that bacteriophages use their TSP only to clear their way to a secondary receptor. Rather, O-antigen specific phages may employ enzymatically active TSP as a tool for irreversible LPS membrane binding to initiate subsequent infection steps.