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

Abstract

Summary 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.

High-throughput mapping of the phage resistance landscape inE. coli

“…For example, we used two laboratory E. coli strains that have rough LPS architecture where core oligosaccharide is the terminal part of the LPS. However, it is known that the genetic and structural diversity of LPS and the repeat structure O-polysaccharide attached to LPS (to form smooth LPS) is very large in pathogenic and environmental isolates of Enterobacteriaceae, and may impact phage infectivity [47,57,[199][200][201][202]. The genetic screens presented in this work may aid in filling the knowledge gap on phage interaction with different O-antigens and its impact on phage infectivity and resistance.…”

“…Bacterial sensitivity/resistance to phages is typically characterized using phenotypic methods such as cross-infection patterns against a panel of phages [14][15][16][17][18][19][20][21][22][23][24][25][26][27] or by whole-genome sequencing of phage-resistant mutants [28][29][30][31][32]. As such, our understanding of bacterial resistance mechanisms against phages remains limited, and the field is therefore in need of improved methods to characterize phage-host interactions, determine the generality and diversity of phage resistance mechanisms in nature, and identify the degree of specificity for each bacterial resistance mechanism across diverse phage types [13,25,26,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”

Genes affecting progression of bacteriophage P22 infection in Salmonella identified by transposon and single gene deletion screens

“…This is not surprising, as previous reports have shown that LPS is critical for P22 entry (Liu et al ., ). LPS has also been shown to contribute to particle ejection in vitro (Andres et al ., ); recently reviewed in (Broeker and Barbirz, ). However, LPS causes a slow and inefficient triggering of P22 ejection alone, whereas outer membrane proteins are critical for accelerating this process and for E‐protein release, which is essential for infection (Jin et al ., ).…”

Increasing the Affinity of an O-Antigen Polysaccharide Binding Site in Shigella Flexneri Bacteriophage Sf6 Tailspike Protein

“…In their functional context, bacteriophage TSPs are indispensable tail parts rendering the maturep hage into an efficient, multivalent particlef or adsorption to ab acterial surfacet os tart infection. [74,75] Multivalent binding observed for Sf6TSPo nt he activated SfY polysaccharide surface resembles the interactions of Sf6 bacteriophage with LPS covered S. flexneri surfaces. Here, the typical bimodal O-polysaccharidec hain length distribution found in S. flexneri LPS resultsi naheterogeneous glycan ligand surface.…”