Cell wall hydrolases – enzymes that precisely cleave the bacterial cell wall.

Abstract. As biology becomes increasingly data-driven, so does the field of phage lysins, enzymes that degrade bacterial cell walls and offer promising alt

Lysins are peptidoglycan hydrolases with great promise as novel and highly differentiated biotherapeutic agents. Here, we characterize LYSG101, a chimeric lysin active against all <i>Staphylococcus</i>...

Treatment of mycobacterial infections is difficult due to poor penetration of antibiotics across the complex cell envelope. We engineered phage-inspired lytic proteins, mycolysins, that selectively breach this barrier and enable rapid bacterial clearance in pulmonary and wound infection models, highlighting a programmable biologic platform to enhance and shorten existing therapies.

Antimicrobial resistance in pathogenic mycobacteria remains a critical challenge due to poor drug penetration through their complex cell wall, which n…

ABSTRACTPseudomonas aeruginosa is a leading cause of nosocomial infections, including pneumonia and urinary tract infections, and the primary cause of morbidity and mortality in cystic fibrosis patients. The emergence of multidrug-resistant strains makes these infections life-threatening. To overcome this challenge, lysocins can be employed as novel antipseudomonals. Lysocins use components of the pyocin antimicrobial system to deliver bacteriophage lysins to their peptidoglycan substrate in Pseudomonas. Peptidoglycan cleavage causes membrane destabilization, cytoplasmic leakage, and disruption of the proton motive force, thereby killing the cell. In our previous proof-of-concept study, the PyS2-GN4 lysocin killed only one-third of P. aeruginosa strains due to the targeted receptor. This limitation can now be circumvented by engineering second-generation lysocins that bind and translocate through highly conserved Pseudomonas-specific receptors. One lysocin, PyS5-I-GN4, uses a single domain from pyocin S5 to deliver the GN4 lysin through the conserved ferric pyochelin transporter, consequently killing 95% of multidrug-resistant clinical isolates tested. Importantly, PyS5-I-GN4 displayed antibiofilm properties and was bactericidal in serum and lung surfactant. Serum inactivation observed for lysins is not seen for lysocins, making this approach more effective for treating systemic Gram-negative bacterial infections. Despite its broadened pseudomonal strain coverage, PyS5-I-GN4 demonstrated narrow-spectrum antibacterial activity toward P. aeruginosa only and lacked cytotoxicity toward human cells. A single dose of lysocin was protective and reduced bacteria multiple log10-fold in the lungs and secondary organs in a neutropenic murine lung infection model. These findings support lysocins as therapeutics for P. aeruginosa and provide insight into designing future constructs for other Gram-negative pathogens.

Picobirnaviruses (PBVs) are double-stranded RNA viruses frequently detected in human and animal enteric viromes. Associations of PBVs with enteric ...

Our findings establish SMphage-derived lysins as a conserved, therapeutically valuable class of antimicrobials with inherent broad-spectrum potential across diverse streptococcal pathogens. Building on the previously demonstrated in vivo efficacy of PlySK1249 against S. dysgalactiae and S. agalactia …

Phage-derived lysins represent a novel, non-traditional therapeutic agent against multidrug-resistant bacteria. However, engineering lysins with broad host range remain poorly addressed. Previously, we reported that the chimeric lysin ClyR, which harbors the CHAP catalytic domain of PlyC lysin (PlyC …

The escalating misuse of antibiotics has precipitated a dramatic rise in bacterial drug resistance, rendering conventional therapies increasingly ineffective. In this post-antibiotic era, phage lysins have emerged as a novel class of antimicrobial agents, attracting significant attention for their p …

Precisio will use its proprietary AI/ML-guided Zeus ™-LysiThru™ platform technologies to discover engineered lysins with superior activity and specificity with funding support from the Gates Foundation. Lysins are a promising new family of enzymes (cell wall hydrolase-based...

Precisio Biotix Therapeutics has received funding from the Gates Foundation aimed at developing engineered lysins to combat bacterial vaginosis, aiming for targeted healthcare solutions.

npj Antimicrobials and Resistance - Antibiotics re-booted—time to kick back against drug resistance

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The phage lysin field has done nothing but grow in the last decades. As a result, many different research groups around the world are contributing to the field, often with certain methodological differences that pose a challenge to the interpretation and comparison of results. In this work, we prese …

Currently, multidrug-resistant (MDR) bacterial wound infections (WIs) are an extremely challenging clinical problem for physicians. Recently, compared to traditional single liquid delivery drugs, the study of five novel drug delivery systems (i.e., hydrogel, liposomes, electrospun fibers, nanopartic …