Year: 2024
Type: article
Abstract: Helicobacter pylori is a gram-negative bacterium that chronically infects ∼50% of the world’s population [1]. H. pylori colonization in the stomach can lead to gastric inflammation (gastritis) and an increased risk for gastric cancer, peptic ulcer disease, and mucosa-associated lymphoid tissue lymphoma. Gastric cancer is the third leading cause of cancer-related death worldwide, and H. pylori is classified as a type I carcinogen by the World Health Organization [2, 3]. H. pylori strains that harbor the cag pathogenicity island, a 40-kb chromosomal region that encodes a Type IV Secretion System (T4SS) and the secreted effector protein CagA, are more frequently associated with severe disease. CagA is the only protein known to be translocated by the Cag T4SS and once inside cells causes numerous alterations in cell signaling, linking it to malignant transformation. How the T4SS physically translocates CagA is not understood. T4SS complexes are challenging structural candidates because they span the inner and outer membranes of gram-negative bacteria making them difficult to purify as intact complexes. T4SSs in Gram-negative bacteria contain a minimum of 12 components. These proteins typically organize into an outer membrane core complex (OMCC), an inner membrane complex (IMC), and in some species an extracellular pilus. The H. pylori OMCC is inserted in the bacterial outer membrane and spans periplasm between the bacterial outer and inner membranes. The OMCC is organized into three subassemblies: the outer membrane cap, the periplasmic ring, and the stalk. Considerable structural biology work has been done to characterize the T4SS OMCC. The OMCC is composed of a 14-fold symmetrical outer membrane cap and a 17-fold symmetrical periplasmic ring, and stalk that has yet to be structurally or compositionally characterized [4]. Using an improved Cag T4SS purification strategy and vitrification protocol, we can now visualize the Cag T4SS stalk. This work focuses on characterizing the structure of the stalk using single particle cryo-electron microscopy analysis and highlights additional symmetry mismatches found in the Cag T4SS OMCC.
Source: Microscopy and Microanalysis
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4400999254