Evidence map›Paper›PMID 39044206›Full record

ArticleJournal of biomedical science2024

Development of novel antimicrobials with engineered endolysin LysECD7-SMAP to combat Gram-negative bacterial infections.

Daria V Vasina, Nataliia P Antonova, Vladimir A Gushchin, Andrey V Aleshkin, Mikhail V Fursov, Anastasiia D Fursova, Petya G Gancheva, Igor V Grigoriev, Pavel Grinkevich, Alexey V Kondratev and 20 more

Abstract read
In one paragraph

Article in Journal of biomedical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Phage and endolysin-based inhibition ofFrontiers in cellular and infection microbiology · 2026
    Review
  8. Wound-Healing Potential of Engineered Lysin GRC-ML07 inAntibiotics (Basel, Switzerland) · 2025
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Daria V VasinaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia. d.v.vasina@gmail.com.ORCID http://orcid.org/0000-0003-1965-0700
Nataliia P AntonovaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Vladimir A GushchinN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Andrey V AleshkinG.N. Gabrichevsky Moscow Research Institute for Epidemiology and Microbiology, Moscow, Russia.
Mikhail V FursovState Research Center for Applied Microbiology and Biotechnology, Obolensk, Russia.
Anastasiia D FursovaState Research Center for Applied Microbiology and Biotechnology, Obolensk, Russia.
Petya G GanchevaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Igor V GrigorievN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Pavel GrinkevichFaculty of Science, University of South Bohemia in Ceske Budejovice, Ceske Budejovice, Czech Republic.
Alexey V KondratevN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Alexey V KostarnoyN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Anastasiya M LendelN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Valentine V MakarovCentre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Moscow, Russia.
Maria A NikiforovaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Andrei A PochtovyiN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Tatiana PrudnikovaFaculty of Science, University of South Bohemia in Ceske Budejovice, Ceske Budejovice, Czech Republic.
Timofey A RemizovN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Natalia V ShevlyaginaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Andrei E SiniavinN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Nina S SmirnovaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Alexander A TerechovN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Artem P TkachukN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Evgeny V UsachevN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Aleksei M VorobevG.N. Gabrichevsky Moscow Research Institute for Epidemiology and Microbiology, Moscow, Russia.
Victoria S YakimakhaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Sergey M YudinCentre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Moscow, Russia.
Anastasia A ZackharovaN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Vladimir G ZhukhovitskyN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Denis Y LogunovN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
Alexander L GintsburgN.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.

Funding

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency Contract no. 0373100122120000008 of 08 April 2020Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency no. 0373100122119000013 of 15 May 2019
6 · The paper itself

Abstract

backgroundAmong the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens.

methodsThe study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats.

resultsIn this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed.

conclusionsOur studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages.

Indexed as

EndopeptidasesGram-Negative BacteriaGram-Negative Bacterial InfectionsMice, Inbred BALB CAnimalsAnti-Bacterial AgentsMaleMiceProtein EngineeringRatsAnti-Bacterial AgentsendolysinEndopeptidasesDosage formsEngineered endolysinEnzyme-based antibacterialGram-negative bacteriaPreclinical efficacy

Identifiers

PMID39044206
PMCPMC11267749

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.