Phages are highly abundant in the environment and pose a major threat for bacteria. Therefore, bacteria have evolved sophisticated defence systems to withstand phage attacks. Here, we describe a previously unknown mechanism by which mono- and diderm bacteria survive infection with diverse lytic phages. Phage exposure leads to a rapid and near-complete conversion of walled cells to a cell-wall-deficient state, which remains viable in osmoprotective conditions and can revert to the walled state. While shedding the cell wall dramatically reduces the number of progeny phages produced by the host, it does not always preclude phage infection. Altogether, these results show that the formation of cell-wall-deficient cells prevents complete eradication of the bacterial population and suggest that cell wall deficiency may potentially limit the efficacy of phage therapy, especially in highly osmotic environments or when used together with antibiotics that target the cell wall.

The prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology. In all previously described species, chemoreceptors organize into a hexagonal (P6 symmetry) extended array. Here, we report an alternative symmetry (P2) of the chemotaxis apparatus that emerges from a strict linear organization of the histidine kinase CheA in Treponema denticola cells, which possesses arrays with the highest native curvature investigated thus far. Using cryo-ET, we reveal that Td chemoreceptor arrays assume an unusual arrangement of the supra-molecular protein assembly that has likely evolved to accommodate the high membrane curvature. The arrays have several atypical features, such as an extended dimerization domain of CheA and a variant CheW-CheR-like fusion protein that is critical for maintaining an ordered chemosensory apparatus. Furthermore, the previously characterized Td oxygen sensor ODP influences CheA ordering. These results suggest a greater diversity of the chemotaxis signaling system than previously thought.

The prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology, but most insights have been obtained from only a few model organisms. In all previously described species, chemoreceptors organize with the histidine kinase (CheA) and coupling protein (CheW) into a hexagonal (P6 symmetry) extended array that is considered universal among archaea and bacteria. Here, for the first time, we apply cryo-electron tomography to whole Treponema denticola (Td) cells to investigate the structure of a spirochete (F2) chemotaxis system. The Td chemoreceptor arrays assume a truly unusual arrangement of the supra-molecular protein assembly that has likely evolved to accommodate the high membrane curvature present in spirochetes. A two-fold (P2) symmetry of the chemotaxis apparatus in Td emerges from a strict linear organization of the kinase CheA, which generates arrays that run parallel to the cell axis. The arrays have several additional atypical features, such as an extended dimerization domain of CheA and a variant CheW-CheR-like fusion protein that is critical for maintaining an ordered, functional chemosensory apparatus in an extremely curved cell. Furthermore, the previously characterized Td oxygen sensor ODP influences array integrity and its loss substantially orders CheA. These results demonstrate the importance of examining chemotaxis structures of non-model organisms in vivo and suggest a greater diversity of this signaling system than previously thought.

Phages are highly abundant in the environment and a major threat for bacteria. Therefore, bacteria have evolved sophisticated defense systems to withstand phage attacks. Here, we describe a previously unknown mechanism by which mono- and diderm bacteria survive infection with diverse lytic phages. Phage exposure leads to a rapid and near complete conversion of walled cells to a cell wall-deficient state, which remain viable in osmoprotective conditions and can revert to the walled state. While shedding the cell wall dramatically reduces the number of progeny phages produced by the host, it does not always preclude phage infection. Altogether, these results show that the formation of cell wall-deficient cells prevents complete eradication of the bacterial population and suggest that cell wall-deficiency may limit the efficacy of phage therapy, especially in highly osmotic environments or when used together with antibiotics that target the cell wall.

Bacteriophages are gaining increased attention for their potential application as agents to combat antibiotic-resistant infections. However, isolation and characterization of new phages are time consuming and limited by currently used methods.