Anti-staphylococcal lysin, LSVT-1701, activity: In vitro susceptibility of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) clinical isolates from around the world collected from 2002 to 2019

Huang, David B.; Sader, Hélio S.; Rhomberg, Paul R.; Gaukel, Eric; Borroto–Esoda, Katyna

doi:10.1016/j.diagmicrobio.2021.115471

Cited by 6 publications

(4 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are also three other phage products, AP-PA02 (NCT04596319), YPT-01 (NCT04684641), and BX004-A (NCT05010577), being evaluated in phase 1/2 trials with cystic fibrosis patients with P. aeruginosa infections. For the phage-derived endolysin tonabacase (N-Rephasin SAL200), a new phase 1 trial has been initiated and it has been renamed LSVT-1701 ( 79 , 80 ).…”

Section: Analysis and Discussionmentioning

confidence: 99%

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Butler

Gigante²,

Sati³

et al. 2022

Antimicrob Agents Chemother

174

View full text Add to dashboard Cite

There is an urgent global need for new strategies and drugs to control and treat multi-drug resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes ‘traditional’ and ‘non-traditional’ antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens, mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3 and four under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile and 4 (5%) are non-traditional agents with broad spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens. We believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.

show abstract

Section: Analysis and Discussionmentioning

confidence: 99%

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Butler

Gigante²,

Sati³

et al. 2022

Antimicrob Agents Chemother

174

View full text Add to dashboard Cite

show abstract

“…It showed a broad lytic activity against several Gram-positive pathogens, including MRSA. Similarly, tonabacase is effective against several pathogenic strains of Staphylococcus and Streptococcus [32]. There is no discovery information available for LMS-201, however, it is developed by Lumen Bioscience, Inc [33].…”

Section: Antibodiesmentioning

confidence: 99%

“…Ultimately, lysin presents a promising solution to control bacterial infections as the enzyme is specific to the bacterial cell wall, especially the exposed PG in Gram-positive bacteria. Studies show that endolysins from pathogenic systems effectively lyse pathogens but not normal flora [31,32]. Moreover, high purity of large-scale recombinant endolysin products can be prepared to meet the US Food and Drug Administration regulations.…”

Section: Microbiome-modulating Agentsmentioning

confidence: 99%

“…This fungus is a tomato pathogen, and it has been proposed that Ecp6, a noncatalytic protein secreted from the fungus, can block chitin on its own cell surface to assist the fungal cell in escaping from tomato immunity [92][93][94][95]. Endopeptidase (PDB: 4UZ2) from Thermus thermophilus is another protein that has a higher %identity (32). LysM structures found in Ecp6, Endopeptidase, and Nabi gp26 have a structurally conserved βααβ.…”

Section: 222mentioning

confidence: 99%

See 1 more Smart Citation

Investigating Novel Streptomyces Bacteriophage Endolysins as Potential Antimicrobial Agents

Maneekul

View full text Add to dashboard Cite

As antibiotic resistance has become a major global threat, the World Health Organization has urgently called scientists for alternative strategies for control of bacterial infections. Endolysin, a protein encoded by a phage gene, can degrade bacterial peptidoglycan (PG). Currently, there are three endolysin products in the clinical phase. We, thus, are interested in exploring novel endolysins from Streptomyces phages as only a few of them have been experimentally characterized. Using bioinformatics tools, we identified nine functional domain groups from 250 Streptomyces phages putative endolysins. NootNoot gp34 (transglycosylase; Nt34lys), Nabi gp26 (amidase; Nb26lys), Tribute gp42 (PGRP; Tb42lys), and LazerLemon gp35 (CHAP; LL35lys) were selected for experimental studies. We hypothesized that (1) the proteins of interest will have the ability to degrade PG, and (2) the proteins will be potential antimicrobial agents against ESKAPE safe relatives. The results showed that LL35lys, Nb26lys and Tb42lys exhibit PG-degrading activity on zymography and hydrolysis assay. The enzymes (400 µg/mL) can reduce PG turbidity to 32-40%. The killing assay suggested that Tb42lys possess a boarder range (Escherichia coli, Pseudomonas putida, Acinetobacter baylyi and Klebsiella aerogenes). While Nb26lys can attack Gram-negative bacteria, LL35lys can only reduce the growth of the Gram-positive strains with an MIC90 of 2 µg/mL. A higher concentration (≥300 µg/mL) of Nb26lys is needed to treat P. putida and K. aerogenes. Therefore, endolysins from Streptomyces phage have potential as possible antimicrobial agents against ESKAPE bacteria.

show abstract

The crucial relationship between vancomycin minimum inhibitory concentration and therapeutic efficacy against methicillin-resistant coagulase-negative staphylococci

Niinuma,

Kagami,

Sugawara

et al. 2024

Journal of Chemotherapy

View full text Add to dashboard Cite

Anti-staphylococcal lysin, LSVT-1701, activity: In vitro susceptibility of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) clinical isolates from around the world collected from 2002 to 2019

Cited by 6 publications

References 5 publications

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Investigating Novel Streptomyces Bacteriophage Endolysins as Potential Antimicrobial Agents

The crucial relationship between vancomycin minimum inhibitory concentration and therapeutic efficacy against methicillin-resistant coagulase-negative staphylococci

Contact Info

Product

Resources

About