Evidence map›Paper›PMID 34526600›Full record

ArticleScientific reports2021

Hybrid derivative of cathelicidin and human beta defensin-2 against Gram-positive bacteria: A novel approach for the treatment of bacterial keratitis.

Darren Shu Jeng Ting, Eunice Tze Leng Goh, Venkatesh Mayandi, Joanna M F Busoy, Thet Tun Aung, Mercy Halleluyah Periayah, Mario Nubile, Leonardo Mastropasqua, Dalia G Said, Hla M Htoon and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
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  9. Frontiers in cellular and infection microbiology · 2023
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  13. Article
  14. Article
  15. Non-antibiotic management of bacterial keratitis.Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society
    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

15 authors at 5 institutions in 4 countries.

Darren Shu Jeng TingAcademic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.
Eunice Tze Leng GohAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Venkatesh MayandiAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Joanna M F BusoyAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Thet Tun AungAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Mercy Halleluyah PeriayahAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Mario NubileOphthalmic Clinic, University "G d'Annunzio" of Chieti-Pescara, Chieti, Italy.
Leonardo MastropasquaOphthalmic Clinic, University "G d'Annunzio" of Chieti-Pescara, Chieti, Italy.
Dalia G SaidAcademic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.
Hla M HtoonAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Veluchamy Amutha BarathiAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Roger W BeuermanAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Rajamani LakshminarayananAnti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore.
Imran Mohammed *Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.
Harminder S Dua *Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK. Harminder.Dua@nottingham.ac.uk.
Singapore Eye Research Institute · SGUniversity of Nottingham · GBUniversity of Chieti-Pescara · ITQueen's Medical Centre · GBUniversity of Tennessee Health Science Center · US

Funding

Medical Research Council MRC-CIC_2019-028Medical Research Council MR/T001674/1
6 · The paper itself

Abstract

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC = 12.5-25.0 μg/ml (5.2-10.4 μM)] and S. epidermidis [MIC = 12.5 μg/ml (5.2 μM)], and moderate efficacy against P. aeruginosa [MIC = 25-50 μg/ml (10.4-20.8 μM)]. CaD23 (at 25 μg/ml or 2× MIC) killed all the bacteria within 30 min, which was 8 times faster than amikacin (25 μg/ml or 20× MIC). After 10 consecutive passages, S. aureus (ATCC SA29213) did not develop any antimicrobial resistance (AMR) against CaD23 whereas it developed significant AMR (i.e. a 32-fold increase in MIC) against amikacin, a commonly used treatment for BK. Pre-clinical murine studies showed that CaD23 (0.5 mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log

Indexed as

Amino Acid SequenceAnti-Bacterial Agentsbeta-DefensinsCathelicidinsCell LineCell SurvivalDisease ManagementDrug DiscoveryDrug Resistance, BacterialGram-Positive BacteriaHemolysisHumansKeratitisMicrobial Sensitivity TestsAnti-Bacterial Agentsbeta-DefensinsCathelicidinsDEFB4A protein, human

Identifiers

PMID34526600
PMCPMC8443647
OpenAlexW3156824858

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.