Advanced engineering of third-generation lysins and formulation strategies for clinical applications
Vincent De Maesschalck,Vincent De Maesschalck,Diana Gutiérrez,Jan Paeshuyse,Rob Lavigne,Yves Briers +5 more
TLDR
This review focuses on third-generation and advanced formulation strategies that are developed to treat infections, ranging from topical to systemic applications, and may fully unlock the potential of lysin therapy and will propel it as a true antibiotic alternative or supplement.Abstract:
One of the possible solutions for the current antibiotic resistance crisis may be found in (often bacteriophage-derived) peptidoglycan hydrolases. The first clinical trials of these natural enzymes, coined here as first-generation lysins, are currently ongoing. Moving beyond natural endolysins with protein engineering established the second generation of lysins. In second-generation lysins, the focus lies on improving antibacterial and biochemical properties such as antimicrobial activity and stability, as well as expanding their activities towards Gram-negative pathogens. However, solutions to particular key challenges regarding clinical applications are only beginning to emerge in the third generation of lysins, in which protein and biochemical engineering efforts focus on improving properties relevant under clinical conditions. In addition, increasingly advanced formulation strategies are developed to increase the bioavailability, antibacterial activity, and half-life, and to reduce pro-inflammatory responses. This review focuses on third-generation and advanced formulation strategies that are developed to treat infections, ranging from topical to systemic applications. Together, these efforts may fully unlock the potential of lysin therapy and will propel it as a true antibiotic alternative or supplement.read more
Citations
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β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium.
Jed F. Fisher,Shahriar Mobashery +1 more
TL;DR: A recent review as discussed by the authors addresses the current breadth of biochemical and microbiological efforts to preserve the future of β-lactam antibiotics through a better understanding of how S. aureus protects the enzyme targets of the β-Lactams, the penicillin-binding proteins.
Journal ArticleDOI
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms.
Ana Catarina Duarte,Ana Catarina Duarte,Lucía Fernández,Lucía Fernández,Vincent De Maesschalck,Vincent De Maesschalck,Diana Gutiérrez,Ana B. Campelo,Yves Briers,Rob Lavigne,Ana Rodríguez,Ana Rodríguez,Pilar García,Pilar García +13 more
TL;DR: In this paper, the combination of a phage-derived lytic protein, CHAPSH3b, and the virulent bacteriophage phiIPLA-RODI was investigated for the treatment of Staphylococcus aureus biofilms.
Journal ArticleDOI
Phage Therapy in the 21st Century: Is There Modern, Clinical Evidence of Phage-Mediated Efficacy?
TL;DR: For example, the authors found that about half of 70 human phage treatment reports published in English thus far in the 2000s are suggestive of phage-mediated anti-bacterial infection efficacy.
Journal ArticleDOI
Biological foundations of successful bacteriophage therapy
Carola Venturini,Aleksandra Petrovic Fabijan,Alicia Fajardo Lubian,Stefanie Barbirz,Jonathan R. Iredell +4 more
TL;DR: This review aims to cover key aspects of bacterium–phage interactions that affect bacterial killing by describing the most relevant published literature and detailing the current knowledge gaps most likely to influence therapeutic success.
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Application of bacteriophages and endolysins in aquaculture as a biocontrol measure
Ramesh Nachimuthu,Madhav Madurantakam Royam,Prasanth Manohar,Prasanth Manohar,Sebastian Leptihn,Sebastian Leptihn +5 more
TL;DR: This review has focused on collecting pieces of evidence to support the application of bacteriophages or phage-derived endolysins in Aquaculture to fight bacterial infections in a post-antibiotic era and summarised the prospects of phage applications in aquaculture.
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