Microbial-derived products as potential new antimicrobials.

Due to the continuing global concerns involving antibiotic resistance, there is a need for scientific forums to assess advancements in the development of antimicrobials and their alternatives that might reduce development and spread of antibiotic resistance among bacterial pathogens. The objectives of the 2 International Symposium on Alternatives to Antibiotics were to highlight promising research results and novel technologies that can provide alternatives to antibiotics for use in animal health and production, assess challenges associated with their authorization and commercialization for use, and provide actionable strategies to support their development. The session on microbial-derived products was directed at presenting novel technologies that included exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials, probiotics development via fecal microbiome transplants among monogastric production animals such as chickens and mining microbial sources such as bacteria or yeast to identify new antimicrobial compounds.

Engineered endolysin-based "Artilysins" to combat multidrug-resistant gram-negative pathogens.

The global threat to public health posed by emerging multidrug-resistant bacteria in the past few years necessitates the development of novel approaches to combat bacterial infections. Endolysins encoded by bacterial viruses (or phages) represent one promising avenue of investigation. These enzyme-based antibacterials efficiently kill Gram-positive bacteria upon contact by specific cell wall hydrolysis.

Art-175 is a highly efficient antibacterial against multidrug-resistant strains and persisters of Pseudomonas aeruginosa.

Artilysins constitute a novel class of efficient enzyme-based antibacterials. Specifically, they covalently combine a bacteriophage-encoded endolysin, which degrades the peptidoglycan, with a targeting peptide that transports the endolysin through the outer membrane of Gram-negative bacteria. Art-085, as well as Art-175, its optimized homolog with increased thermostability, are each composed of the sheep myeloid 29-amino acid (SMAP-29) peptide fused to the KZ144 endolysin.

Structure of the receptor-binding protein of bacteriophage det7: a podoviral tail spike in a myovirus.

A new Salmonella enterica phage, Det7, was isolated from sewage and shown by electron microscopy to belong to the Myoviridae morphogroup of bacteriophages. Det7 contains a 75-kDa protein with 50% overall sequence identity to the tail spike endorhamnosidase of podovirus P22. Adsorption of myoviruses to their bacterial hosts is normally mediated by long and short tail fibers attached to a contractile tail, whereas podoviruses do not contain fibers but attach to host cells through stubby tail spikes attached to a very short, noncontractile tail.

Optimization of blood-myocardial contrast in 3D true FISP cardiac imaging at 1.5 T.

Three-dimensional (3D) steady-state free precession (SSFP) MRI sequences are often applied to visualize both intra- and extracardiac pathologies. In the present study the contrast behavior of 3D true fast imaging with steady precession (True-FISP) sequences for cardiac imaging was optimized in numerical simulations and compared with measurements obtained in eight healthy volunteers on a 1.5 T whole-body scanner.

Emergency donor heart protection: application of the port access catheter technique using a pig heart transplantation model.

Background: Organ shortage limits the number of transplantations, and donor deterioration may precede and often prevent conventional organ preservation. This study evaluates in situ perfusion as a bedside method for cardiac allograft procurement in a large animal model.

Methods: Thirty Landrace pigs (42 +/- 7 kg) were studied.

Sodium-hydrogen inhibitor cariporide (HOE 642) improves in situ protection of hearts from non-heart-beating donors.

Background: Reperfusion injury is a vital problem in non-heart-beating donor (NHBD) organs. The sodium-hydrogen inhibitor cariporide is thought to improve cellular integrity after ischemia and reperfusion. Recently, we demonstrated the possibility of preserving hearts with in situ perfusion after circulatory death.

The structure of the receptor-binding domain of the bacteriophage T4 short tail fibre reveals a knitted trimeric metal-binding fold.

Adsorption of T4 bacteriophage to the Escherichia coli host cell is mediated by six long and six short tail fibres. After at least three long tail fibres have bound, short tail fibres extend and bind irreversibly to the core region of the host cell lipo-polysaccharide (LPS), serving as inextensible stays during penetration of the cell envelope by the tail tube. The short tail fibres consist of a parallel, in-register, trimer of gene product 12 (gp12).

A transient N-O-linked Pauson-Khand strategy for the synthesis of the deschloro carbocyclic core of the palau'amines and styloguanidines.

A stereocontrolled route to the deschloro cyclopentyl core of the palau'amines and styloguanidines has been developed. This strategy makes use of the intramolecular Pauson-Khand cyclization of an enyne with a "transient N-O tether" to construct a five-membered carbocycle in a diastereoselective fashion. [reaction: see text]

Review: conformation and folding of novel beta-structural elements in viral fiber proteins: the triple beta-spiral and triple beta-helix.

Apart from alpha-helical coiled coils and the collagen triple helices, fibrous proteins can contain beta-structure in various conformations. Elongated enzymes such as pectate lyase and the bacteriophage P22 tailspike protein contain single-stranded beta-helices. Virus and bacteriophage fibers, which are often trimeric, have been shown to contain novel triple-stranded beta-structures such as the triple beta-spiral and the triple beta-helix.