Last update 01 Nov 2024

Lysostaphin

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with Lysostaphin

Recombinant lysostaphin(Shanghai High-Tech United Biological Technology Research Development Co Ltd)

Target

Lysostaphin

Mechanism

Lysostaphin stimulants

Active Org.

Shanghai Hi-Tech United Biotechnology R&D Co. Ltd.

Originator Org.

Shanghai Hi-Tech United Biotechnology R&D Co. Ltd.

Active Indication

MRSA - Methicillin resistant Staphylococcus aureus infection [+1]

Inactive Indication-

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Lysostaphin

Target

Lysostaphin

Mechanism

Lysostaphin stimulants

Active Org.-

Originator Org.

NXXI SUB LLC

Active Indication-

Inactive Indication

Staphylococcal Infections

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Lysostaphin

CTR20230948 / RecruitingPhase 3

评价重组溶葡萄球菌酶涂剂治疗深Ⅱo烧伤创面合并耐甲氧西林金黄色葡萄球菌MRSA感染的有效性和安全性的多中心、随机、盲法评估、阳性药对照IIIb期临床预试验

[Translation] A multicenter, randomized, blinded, active-controlled phase IIIb clinical pilot trial to evaluate the efficacy and safety of recombinant lysostaphin paint in the treatment of deep IIo burn wounds complicated with methicillin-resistant Staphylococcus aureus (MRSA) infection

主要目的：初步评价重组溶葡萄球菌酶涂剂治疗深Ⅱo烧伤创面合并MRSA感染的完全创面闭合时间（天）。次要目的：评价重组溶葡萄球菌酶涂剂治疗深Ⅱo烧伤创面合并MRSA感染的完全创面闭合发生率、创面愈合率、细菌学疗效、综合疗效和安全性。

[Translation]

Primary objective: To preliminarily evaluate the time (days) for complete wound closure of deep Ⅱo burn wounds complicated with MRSA infection treated with recombinant lysostaphin. Secondary objective: To evaluate the incidence of complete wound closure, wound healing rate, bacteriological efficacy, comprehensive efficacy and safety of recombinant lysostaphin in the treatment of deep Ⅱo burn wounds complicated with MRSA infection.

Start Date20 Sep 2023

Sponsor / Collaborator

Shanghai Hi-Tech United Biotechnology R&D Co. Ltd.

CTR20130659 / CompletedPhase 3

外用重组溶葡萄球菌酶治疗深Ⅱo烧伤创面合并MRSA感染的疗效和安全性的多中心随机双盲Ⅲ期临床试验

[Translation] A multicenter, randomized, double-blind, phase III clinical trial on the efficacy and safety of topical recombinant lysostaphin in the treatment of deep Ⅱo burn wounds complicated with MRSA infection

评价外用重组溶葡萄球菌酶治疗深Ⅱo烧伤创面合并金葡菌(包括MRSA)感染的有效性和安全性。

[Translation]

To evaluate the efficacy and safety of topical recombinant lysostaphin in the treatment of deep Ⅱo burn wounds complicated with Staphylococcus aureus (including MRSA) infection.

Start Date23 Feb 2011

Sponsor / Collaborator

Shanghai Hi-Tech United Biotechnology R&D Co. Ltd.

CTR20150550 / CompletedPhase 2

外用重组溶葡萄球菌酶治疗深Ⅱo烧伤创面合并耐甲氧西林金黄色葡萄球菌(MRSA)感染的有效性和安全性Ⅱ期临床试验

[Translation] Phase II clinical trial on the efficacy and safety of topical recombinant lysostaphin in the treatment of deep Ⅱo burn wounds complicated with methicillin-resistant Staphylococcus aureus (MRSA) infection

评价外用重组溶葡萄球菌酶治疗深Ⅱo烧伤创面合并MRSA感染的临床有效性和安全性，探索有效治疗剂量，为Ⅲ期临床试验提供科学依据。

[Translation]

To evaluate the clinical efficacy and safety of topical recombinant lysostaphin in the treatment of deep IIo burn wounds complicated with MRSA infection, explore the effective therapeutic dose, and provide a scientific basis for phase III clinical trials.

Start Date10 Sep 2007

Sponsor / Collaborator

Shanghai Hi-Tech United Biotechnology R&D Co. Ltd.

100 Clinical Results associated with Lysostaphin

100 Translational Medicine associated with Lysostaphin

0 Patents (Medical) associated with Lysostaphin

Literatures (Medical) associated with Lysostaphin

30 Jun 2024·Drug Discoveries & Therapeutics

Induction of acute silkworm hemolymph melanization by <i>Staphylococcus aureus</i> treated with peptidoglycan-degrading enzymes

Article

Author: Sato, Eri ; Sugita, Takashi ; Matsumoto, Yasuhiko

Staphylococcus aureus, a Gram-positive bacterium, causes inflammatory skin diseases, such as atopic dermatitis, and serious systemic diseases, such as sepsis. In the skin and nasal environment, peptidoglycan (PGN)-degrading enzymes, including lysozyme and lysostaphin, affects S. aureus PGN. However, the effects of PGN-degrading enzymes on the acute innate immune-inducing activity of S. aureus have not yet been investigated. In this study, we demonstrated that PGN-degrading enzymes induce acute silkworm hemolymph melanization by S. aureus. Insoluble fractions of S. aureus treated with lysozyme, lysostaphin, or both enzymes, were prepared. Melanization of the silkworm hemolymph caused by the injection of these insoluble fractions was higher than that of S. aureus without enzyme treatment. These results suggest that structural changes in S. aureus PGN caused by PGN-degrading enzymes affect the acute innate immune response in silkworms.

12 Dec 2023·Microbiology Spectrum

Engineered probiotic Lactobacillus plantarum WCSF I for monitoring and treatment of Staphylococcus aureus infection

Article

Author: Li, Haoran ; Wang, Qian ; Qi, Qingsheng ; Jia, Minjun

ABSTRACTLactobacillus plantarum is one of the most thoroughly researched species of the genus Lactobacillus , which possesses the characteristics of easy genetic transformation, high-density growth, and high intestinal tract survival. L. plantarum has been proven to play a potential role as a probiotic delivery vector. Staphylococcus aureus is a common Gram-positive pathogenic bacterium. It uses an autoinducer peptide (AIP) produced by its Agr quorum-sensing (AgrQS) system to sense the population density. Using the quorum-sensing mechanism exclusive to S. aureus , we constructed an AgrQS system in L. plantarum WCSF induction and killing modules based on AIP sensing and regulation so that L. plantarum could effectively eliminate S. aureus when detecting exogenous AIP at nanomolar concentrations. By optimizing the expression strength of the two-component system AgrAC using different L. plantarum -derived promoters and replacing the core promoter of the AgrA-activating promoter, the activation strength of AgrQS increased from the initial 1.2-fold to 5.3-fold. By introducing the signal peptide N20-guided lysostaphin aureus protein, engineered L. plantarum was able to effectively control the release of lysostaphin aureus protein and inhibit the growth of S. aureus . For the first time, engineered L. plantarum can detect and treat S. aureus infection, laying the groundwork for the future development of engineered probiotics for the monitoring and therapy of intestinal pathogens. IMPORTANCE Bacterial infection and the emergence of drug-resistant strains are major problems in clinical treatment. Staphylococcus aureus , which typically infects the skin and blood of animals, is also a potential intestinal pathogen that needs to be addressed by the emergence of a new treatment approach. Probiotic therapy is the most likely alternative to antibiotic therapy to solve the problem of bacterial drug resistance in clinical practice. In this study, the engineered Lactobacillus plantarum can not only sense the signal AIP to detect S. aureus but also kill S. aureus by secreting the lysostaphin enzyme. Our strategy employed an Agr quorum-sensing genetic circuit to simultaneously detect and treat pathogenic bacteria, which provided a theoretical possibility for solving practical clinical bacterial infection cases in the future.

01 Aug 2023·Biochemical and Biophysical Research Communications

Conserved loop residues−Tyr270 and Asn372 near the catalytic site of the lysostaphin endopeptidase are essential for staphylolytic activity toward pentaglycine binding and catalysis

Article

Author: Sakdee, Somsri ; Angsuthanasombat, Chanan ; Charoenjotivadhanakul, Sathapat ; Imtong, Chompounoot ; Li, Hui-Chun

Lysostaphin endopeptidase cleaves pentaglycine cross-bridges found in staphylococcal cell-wall peptidoglycans and proves very effective in combatting methicillin-resistant Staphylococcus aureus. Here, we revealed the functional importance of two loop residues, Tyr²⁷⁰ in loop 1 and Asn³⁷² in loop 4, which are highly conserved among the M23 endopeptidase family and are found close to the Zn²⁺-coordinating active site. Detailed analyses of the binding groove architecture together with protein-ligand docking showed that these two loop residues potentially interact with the docked ligand-pentaglycine. Ala-substituted mutants (Y270A and N372A) were generated and over-expressed in Escherichia coli as a soluble form at levels comparable to the wild type. A drastic decrease in staphylolytic activity against S. aureus was observed for both mutants, suggesting an essential role of the two loop residues in lysostaphin function. Further substitutions with an uncharged polar Gln side-chain revealed that only the Y270Q mutation caused a dramatic reduction in bioactivity. In silico predicting the effect of binding site mutations revealed that all mutations displayed a large ΔΔG_bind value, signifying requirements of the two loop residues for efficient binding to pentaglycine. Additionally, MD simulations revealed that Y270A and Y270Q mutations induced large flexibility of the loop 1 region, showing markedly increased RMSF values. Further structural analysis suggested that Tyr²⁷⁰ conceivably participated in the oxyanion stabilization of the enzyme catalysis. Altogether, our present study disclosed that two highly conserved loop residues, loop 1-Tyr²⁷⁰ and loop 4-Asn³⁷², located near the lysostaphin active site are crucially involved in staphylolytic activity toward binding and catalysis of pentaglycine cross-links.

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Lysostaphin

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