PlyKp104, a Novel Phage Lysin for the Treatment of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Other Gram-Negative ESKAPE Pathogens.

Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal.

Isolation of Phage Lysins That Effectively Kill Pseudomonas aeruginosa in Mouse Models of Lung and Skin Infection.

Multidrug resistance (MDR) is rapidly increasing in prevalence among isolates of the opportunistic pathogen , leaving few treatment options. Phage lysins are cell wall hydrolases that have a demonstrated therapeutic potential against Gram-positive pathogens; however, the outer membrane of Gram-negative bacteria prevents most lysins from reaching the peptidoglycan, making them less effective as therapeutics. Nevertheless, a few lysins from Gram-negative bacterial phage can penetrate the bacterial outer membrane with the aid of an amphipathic tail found in the molecule's termini.

Lysostaphin Lysibody Leads to Effective Opsonization and Killing of Methicillin-Resistant Staphylococcus aureus in a Murine Model.

The cell wall of Gram-positive bacteria contains abundant surface-exposed carbohydrate structures that are highly conserved. While these properties make surface carbohydrates ideal targets for immunotherapy, carbohydrates elicit a poor immune response that results primarily in low-affinity IgM antibodies. In a previous publication, we introduced the lysibody approach to address this shortcoming.

Lysibodies are IgG Fc fusions with lysin binding domains targeting wall carbohydrates for effective phagocytosis.

The cell wall of Gram-positive bacteria contains abundant surface-exposed carbohydrate molecules that are highly conserved within and often across species. The potential therapeutic usefulness of high-affinity antibodies to cell wall carbohydrates is unquestioned, however obtaining such antibodies is challenging due to the poor overall immunogenicity of these bacterial targets. Autolysins and phage lysins are peptidoglycan hydrolases, enzymes that have evolved over a billion years to degrade bacterial cell wall.

A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate.

Purpose: To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry.

Methods: Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0.

Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology.

Cell wall anchored virulence factors are critical for infection and colonization of the host by Gram-positive bacteria. Such proteins have an N-terminal leader sequence and a C-terminal sorting signal, composed of an LPXTG motif, a hydrophobic stretch, and a few positively charged amino acids. The sorting signal halts translocation across the membrane, allowing sortase to cleave the LPXTG motif, leading to surface anchoring.

Increased Fundus Autofluorescence and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration: The GAIN Study.

Purpose: To define the role of increased fundus autofluorescence (FAF), a surrogate for lipofuscin content, as a risk factor for progression of geographic atrophy (GA).

Design: Prospective natural history cohort study, the GAIN (Characterization of geographic atrophy progression in patients with age-related macular degeneration).

Methods: setting: Single-center study conducted in Barcelona, Spain.

[Comparison between coproparasitological techniques for the diagnosis of helminth eggs or protozoa oocysts in dogs].

In this study we evaluated the frequency of enteroparasites in pet dogs and their association with age, sex and breed, as well as the efficiency of the Willis-Mollay, Faust, Sedimentation and Direct exam methods. By these methods we processed 401 fecal samples. The samples were positive in the following percentages: Ancylostoma spp.