The Legionella pneumophila effector RavY contributes to a replication-permissive vacuolar environment during infection

Legionella pneumophila is the causative agent of Legionnaires’ Disease and is capable replicating inside phagocytic cells such as mammalian macrophages. The Dot/Icm type IV secretion system is a L. pneumophila virulence factor that is essential for successful intracellular replication. During infection, L. pneumophila builds a replication permissive vacuole by recruiting multiple host molecules and hijacking host cellular signaling pathways, a process mediated by the coordinated functions of multiple Dot/Icm effector proteins. RavY is a predicted Dot/Icm effector protein found to be important for optimal L. pneumophila replication inside host cells. Here, we demonstrate that RavY is a Dot/Icm-translocated effector protein that is dispensable for axenic replication of L. pneumophila , but critical for optimal intracellular replication of the bacteria. RavY is not required for avoidance of endosomal maturation, nor does RavY contribute to the recruitment of host molecules found on replication-permissive vacuoles, such as ubiquitin, RAB1a, and RTN4. Vacuoles containing L. pneumophila ravY mutants promote intracellular survival but limit replication. The replication defect of the L. pneumophila ravY mutant was complemented when the mutant was in the same vacuole as wild type L. pneumophila . Thus, RavY is an effector that is essential for promoting intracellular replication of L. pneumophila once the specialized vacuole has been established.

Stabilization of Near Identical Hydrogen Bonded Octameric Water Clusters in Crystal Structures of Three Distinct Non-Charged Polyamide Macrocyclic Host Molecules

In this paper, we present a comparative analysis of the solid state structures of three well-resolved hydrates of macrocyclic host molecules 1a, 1b, and 2 containing an intrannular amide-aryl substituent (lariat arm) connected to a fixed 26-membered ring in a normal (-NHCOAr, hosts 1a and 1b) or reverse manner (-CONHAr, host 2). Despite different chemical structures, these hosts crystallize as isostructural tetrahydrates in the same P-1 space group. Moreover, their crystals exhibit identical hydrogen bond motifs resulting in a stabilization of an almost identical unusual octameric water cluster built from the cyclic tetramer core and four water molecules, attached sequentially in an “up-and-down” manner. Further analysis reveals that, among the series, the structure of host 2 provides the most suitable environment for the accommodation of this type of water cluster.

Permeation of Hydroxypropyl-Beta-Cyclodextrin and Its Inclusion Complex through Mouse Small Intestine, Determined by a Spectrophotometry

Background: Cyclodextrins (CDs) are commonly used host molecules of inclusion complex. However, due to the lack of sensitive method to determine CDs, the absorption process of CDs remains unclear. Objective: In this study, oleuropein (OL) inclusion complex employing hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) as host molecules was prepared and the formation of inclusion complex was ascertained by FT-IR and DSC. A spectrophotometry was established for the determination of HP-beta-CD, based on the fact that the absorbance of phenolphthalein (PP) decreased in the presence of HP-beta-CD. Methods: The assay conditions were optimized to augment the method sensitivity. Molecular docking was employed to verify the strong interaction between PP and HP-beta-CD. The permeation process of free HP-beta-CD, HP-beta-CD of OL inclusion complex, free OL, and OL in the inclusion complex, was examined, respectively, using an in vitro mouse small intestine model. Results: Though HP-beta-CD possessed hydrophilic outside shell, it could permeate through mouse small intestine quickly with cumulative permeating amount over 90% in 2 h. Free HP-beta-CD, the host molecule HP-beta-CD, and guest molecule OL of the inclusion complex exhibited the consistent permeating profiles across mouse small intestine. Conclusion: The approach for the determination of HP-beta-CD was accurate and precise (%RSD=2.98).

Ionic effects on Supramolecular Hosts: Solvation and Counter-ion Binding in Polar Media

For the progress of synthetic supramolecular chemistry in aqueous solution the design of host molecules soluble in this medium is essential. A possible route is the introduction of ionic residues,...

Recognition of Hydrophilic Molecules in Deep Cavitand Hosts with Water-mediated Hydrogen Bonds

We describe new container host molecules – deep cavitands with benzimidazole walls and ionic feet – to recognize highly hydrophilic guest molecules in water. The aromatic surfaces of the cavity...

Control of guest binding behavior of metal-containing host molecules by ligand exchange

This review describes the control of guest binding behavior of metal-containing host molecules that is driven by ligand exchange reactions at the metal centers. Recently, a vast number of metal-containing...

Principles and applications of cyclodextrin liquid crystals

Cyclodextrin-based liquid crystals combine the versatile properties of macrocyclic host molecules and liquid-crystalline mesophases.

Macrocyclic host molecules with aromatic building blocks: state of art and progress

Macrocyclic host molecule plays the central role in host-guest chemistry and supramolecular chemistry. Highly structural symmetry of macrocyclic host molecules can meet people's pursuit of aesthetics in molecular design, and...