How the phage T4 injection machinery works including energetics, forces, and dynamic pathway

Abstract

The virus bacteriophage T4, from the family Myoviridae, employs an intriguing contractile injection machine to inject its genome into the bacterium Escherichia coli. Although the atomic structure of phage T4 is largely understood, the dynamics of its injection machinery remains unknown. This study contributes a system-level model describing the nonlinear dynamics of the phage T4 injection machinery interacting with a host cell. The model employs a continuum representation of the contractile sheath using elastic constants inferred from atomistic molecular-dynamics (MD) simulations. Importantly, the sheath model is coupled to component models representing the remaining structures of the virus and the host cell. The resulting system-level model captures virus–cell interactions as well as competing energetic mechanisms that release and dissipate energy during the injection process. Simulations reveal the dynamical pathway of the injection process as a “contraction wave” that propagates along the sheath, the energy that powers the injection machinery, the forces responsible for piercing the host cell membrane, and the energy dissipation that controls the timescale of the injection process. These results from the model compare favorably with the available (but limited) experimental measurements.

Tall tails: cryo-electron microscopy of phage tail DNA ejection conduits

“…Phage T4 has a tail that functions as a contractile nanomachine, with a rigid inner tail tube housed within a compressible outer sheath. When the phage is triggered to contract, the outer sheath compresses so that most of the baseplate structure moves and ∼40 nm of the inner tube is exposed [35][36][37]. Biophysical analysis of analogous contractile systems [38] and theoretical calculations are consistent with the assumption that the contractile force generated through the compression of the outer sleeve is sufficient to power the tail tube through the outer membrane [37].…”

Quantitative description of a contractile macromolecular machine

“…Recently, a computational approach that modeled the T4 sheath using Kirchhoff's rod theory with parameters derived from molecular dynamics (MD) simulations of a short fragment of the sheath has been presented (23). The elastic body calculations were parametrized showing the main components and size of the pyocin particle free in solution (extended sheath) and attached to the cell surface (contracted sheath).…”

“…(D) Structure of a six-layer fragment of the pyocin sheath in the contracted state (5) to match the enthalpy of T4 sheath contraction (19) and the contraction time scale of the T6SS (20). Contraction was predicted to proceed via a rapid rotation of sheath subunits before their translation (23,24). Such a sequence of events is incompatible with maintaining the integrity of the sheath subunit, which was implied but not validated in the approach.…”

Phages against Pathogenic Bacterial Biofilms and Biofilm-Based Infections: A Review

“…It has been reported that about 96% of phages are double-stranded DNA genomes with tailed morphology, belonging to the order of Caudovirales [35]. Based on the tail structure, the Caudovirales order can be categorized into three families: Myoviridae (phages with a contractile tail, such as T4-like phages), Siphoviridae (phages with a non-contractile long tail, such as T5-like phages), and Podoviridae (phages with a short tail, such as T7-like phages) [36][37][38].…”