Evidence map›Paper›PMID 30445722›Full record

ArticleViruses2018

Safety Studies of Pneumococcal Endolysins Cpl-1 and Pal.

Marek Harhala, Daniel C Nelson, Paulina Miernikiewicz, Ryan D Heselpoth, Beata Brzezicka, Joanna Majewska, Sara B Linden, Xiaoran Shang, Aleksander Szymczak, Dorota Lecion and 6 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.7field-weighted citation impact, top 5% of its field
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

35 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Avian PathogenicVeterinary sciences · 2025
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. The applications of animal models in phage therapy: An update.Human vaccines & immunotherapeutics · 2023
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article
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

16 authors at 3 institutions in 2 countries.

Marek HarhalaBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. marek.harhala@iitd.pan.wroc.pl.
Daniel C NelsonInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA. nelsond@umd.edu.ORCID 0000-0003-3248-4831
Paulina MiernikiewiczBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. pola@iitd.pan.wroc.pl.
Ryan D HeselpothInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA. rheselpoth@rockefeller.edu.
Beata BrzezickaBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. beatabrzezicka94@gmail.com.
Joanna MajewskaBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. joanna.majewska@iitd.pan.wroc.pl.
Sara B LindenInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA. slinden1@umd.edu.
Xiaoran ShangInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA. sxr520@umd.edu.
Aleksander SzymczakBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. szymczakaleksander@gmail.com.
Dorota LecionBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. dorota.lecion@wp.pl.
Karolina Marek-BukowiecResearch and Development Center, Regional Specialized Hospital, 51-124 Wrocław, Poland. marek-bukowiec@wssk.wroc.pl.
Marlena KłakResearch and Development Center, Regional Specialized Hospital, 51-124 Wrocław, Poland. klak@wssk.wroc.pl.
Bartosz WojciechowiczPerlan Technologies Sp. z o. o., 02-785 Warsaw, Poland. bwojciechowicz@perlan.com.pl.ORCID 0000-0001-8281-3483
Karolina LahuttaBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. karolina.wojtyna@iitd.pan.wroc.pl.
Andrzej KoniecznyResearch and Development Center, Regional Specialized Hospital, 51-124 Wrocław, Poland. andrzej_konieczny@yahoo.com.ORCID 0000-0002-4966-9771
Krystyna DąbrowskaBacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Street 12, 53-114 Wroclaw, Poland. dabrok@iitd.pan.wroc.pl.
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy · PLŁukasiewicz Research Network – PORT Polish Center for Technology Development · PLUniversity of Maryland, Baltimore · US

Funding

Krajowy Naukowy Osrodek Wiodacy 2014-2018Narodowe Centrum Nauki UMO-2015/18/M/NZ6/00412
6 · The paper itself

Abstract

Bacteriophage-derived endolysins have gained increasing attention as potent antimicrobial agents and numerous publications document the in vivo efficacy of these enzymes in various rodent models. However, little has been documented about their safety and toxicity profiles. Here, we present preclinical safety and toxicity data for two pneumococcal endolysins, Pal and Cpl-1. Microarray, and gene profiling was performed on human macrophages and pharyngeal cells exposed to 0.5 µM of each endolysin for six hours and no change in gene expression was noted. Likewise, in mice injected with 15 mg/kg of each endolysin, no physical or behavioral changes were noted, pro-inflammatory cytokine levels remained constant, and there were no significant changes in the fecal microbiome. Neither endolysin caused complement activation via the classic pathway, the alternative pathway, or the mannose-binding lectin pathway. In cellular response assays, IgG levels in mice exposed to Pal or Cpl-1 gradually increased for the first 30 days post exposure, but IgE levels never rose above baseline, suggesting that hypersensitivity or allergic reaction is unlikely. Collectively, the safety and toxicity profiles of Pal and Cpl-1 support further preclinical studies.

Indexed as

AnimalsAnti-Bacterial AgentsAntibodies, ViralDrug-Related Side Effects and Adverse ReactionsEndopeptidasesEpithelial CellsGene Expression ProfilingImmunoglobulin EImmunoglobulin GMacrophagesMiceStreptococcus PhagesAnti-Bacterial AgentsAntibodies, ViralendolysinEndopeptidasesImmunoglobulin EImmunoglobulin GCpl-1endolysinimmune responsePalsafetyStreptococcus pneumoniaetoxicity

Identifiers

PMID30445722
PMCPMC6266847
OpenAlexW2901428074

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.