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In vitro antimicrobial activity of defensins against ocular pathogens.
Abstract: New approaches to antimicrobial therapy for ocular pathogens must overcome organisms that are resistant to current therapeutic modalities. This investigation examined the antimicrobial activity of novel antimicrobial neutrophil peptides (defensins NP-1 and NP-5) against isolates from clinical ocular microbial infections in humans and horses. The test panel of human clinical isolates included Candida albicans, an alpha-hemolytic Streptococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Morganella morganii. The test panel of equine pathogens included three clinical isolates of P aeruginosa and two clinical isolates of Staphylococcus aureus. The equine isolates were chosen for their relative resistance to commonly employed antimicrobial therapy. The two defensins differed markedly in their bactericidal activity. Defensin NP-5, at a 50-micrograms/mL concentration, exhibited minimal bactericidal activity against the majority of isolates of the test panel. The inferior microbicidal activity of NP-5 is consistent with previously published results. However, at this concentration, NP-5 did exhibit appreciable bacteriostatic activity against human ocular pathogens M morganii (74%), alpha-hemolytic Streptococcus (57%), and P aeruginosa (93%) during the 2-hour incubation period. In contrast, defensin NP-1 at 10 micrograms/mL exerted potent microbicidal activity against all isolates, effecting a 2 to 3 log10 decrease in colony-forming units within a 60-minute incubation period. Under the assay conditions employed, these findings demonstrate: (1) two distinct mechanisms by which defensins exert their antimicrobial activity against microbial pathogens associated with clinical ocular disease in humans and horses, and (2) that rabbit defensin NP-1 is a potent antimicrobial agent against a wide array of ocular pathogens.
Publication Date: 1990-06-01 PubMed ID: 2112378DOI: 10.1001/archopht.1990.01070080105044Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research explores the antimicrobial impacts of two novel defensin peptides, NP-1 and NP-5, on common eye pathogens in humans and horses. The results indicate that while NP-5 demonstrates only limited bactericidal activity, NP-1 shows potent antimicrobial effects on all tested pathogens.
Research Objective and Purpose
Anti-microbial resistance poses significant challenges to current therapeutic measures designed for ocular pathogen treatment in both humans and horses. The tested antimicrobial therapy – defensins NP-1 and NP-5 – could potentially address this problem if successful.
Methodology
- The test panel consisted of clinical isolates from human studies which included Candida albicans, an alpha-hemolytic Streptococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Morganella morganii.
- From equine studies, test samples were obtained from three clinical isolates of P aeruginosa and two clinical isolates of Staphylococcus aureus.
- Previous research indicates that the equine pathogens (used in this study) showed relative resistance to common antimicrobial therapy, making them suitable for this exploratory investigation.
Results
- Both defensins showed distinctly different bactericidal activities. Defensin NP-5 demonstrated minimal bactericidal activity against most microbes, consistent with prior studies.
- However, NP-5 did display substantial bacteriostatic activities, by inhibiting bacterial growth when applied at specific concentrations, against M morganii (74%), alpha-hemolytic Streptococcus (57%), and P aeruginosa (93%) during a 2-hour exposure period.
- On the contrary, defensin NP-1 displayed a significant microbicidal activity against all isolates, with a 2 to 3 log10 decrease in colony-forming units within a 60-minute exposure.
Conclusion
This research made two key findings: first, defensins demonstrated differing antimicrobial activities against ocular disease causing microbes in humans and horses; second, defensin NP-1 showed significant potential as an antimicrobial agent across a range of eye pathogens, therefore it may serve as a suitable base for developing novel treatments for ocular infections.
Cite This Article
APA
Cullor JS, Mannis MJ, Murphy CJ, Smith WL, Selsted ME, Reid TW.
(1990).
In vitro antimicrobial activity of defensins against ocular pathogens.
Arch Ophthalmol, 108(6), 861-864.
https://doi.org/10.1001/archopht.1990.01070080105044 Publication
Researcher Affiliations
- Department of Clinical Pathology, School of Veterinary Medicine, University of California, Davis.
MeSH Terms
- Animals
- Bacteria / drug effects
- Bacteria / isolation & purification
- Blood Bactericidal Activity
- Blood Proteins / pharmacology
- Candida albicans / drug effects
- Corneal Ulcer / microbiology
- Corneal Ulcer / veterinary
- Defensins
- Enterobacteriaceae / drug effects
- Eye / microbiology
- Horse Diseases / microbiology
- Horses
- Humans
- Microbial Sensitivity Tests
- Neutrophils
- Pseudomonas aeruginosa / drug effects
- Rabbits
- Staphylococcus aureus / drug effects
- Streptococcus / drug effects
- Streptococcus pneumoniae / drug effects
Citations
This article has been cited 14 times.- Hisey EA, Martins BC, Donnelly CG, Cassano JM, Katzman SA, Murphy CJ, Thomasy SM, Leonard BC. Identification of putative orthologs of clinically relevant antimicrobial peptides in the equine ocular surface and amniotic membrane. Vet Ophthalmol 2023 Apr;26 Suppl 1(Suppl 1):125-133.
- Das T, Joseph J, Jakati S, Sharma S, Velpandian T, Padhy SK, Das VA, Shivaji S, Nayak S, Behera UC, Mishra DK, Gandhi J, Dave VP, Pathengay A. Understanding the science of fungal endophthalmitis - AIOS 2021 Sengamedu Srinivas Badrinath Endowment Lecture. Indian J Ophthalmol 2022 Mar;70(3):768-777.
- Jadi PK, Sharma P, Bhogapurapu B, Roy S. Alternative Therapeutic Interventions: Antimicrobial Peptides and Small Molecules to Treat Microbial Keratitis. Front Chem 2021;9:694998.
- Swift W, Bair JA, Chen W, Li M, Lie S, Li D, Yang M, Shatos MA, Hodges RR, Kolko M, Utheim TP, Scott W, Dartt DA. Povidone iodine treatment is deleterious to human ocular surface conjunctival cells in culture. BMJ Open Ophthalmol 2020;5(1):e000545.
- Marlo TL, Giuliano EA, Sharma A, Mohan RR. Development of a novel ex vivo equine corneal model. Vet Ophthalmol 2017 Jul;20(4):288-293.
- Aldebasi YH, Mohamed HA, Aly SM. Histopathological Studies on Rabbits Infected by Bacteria Causing Infectious Keratitis in Human through Eye Inoculation. Int J Health Sci (Qassim) 2014 Jul;8(3):257-67.
- Kolar SSN, Luca V, Baidouri H, Mannino G, McDermott AM, Mangoni ML. Esculentin-1a(1-21)NH2: a frog skin-derived peptide for microbial keratitis. Cell Mol Life Sci 2015 Feb;72(3):617-627.
- McDermott AM. Defensins and other antimicrobial peptides at the ocular surface. Ocul Surf 2004 Oct;2(4):229-47.
- McDermott AM, Rich D, Cullor J, Mannis MJ, Smith W, Reid T, Murphy CJ. The in vitro activity of selected defensins against an isolate of Pseudomonas in the presence of human tears. Br J Ophthalmol 2006 May;90(5):609-11.
- Gordon YJ, Romanowski EG, McDermott AM. A review of antimicrobial peptides and their therapeutic potential as anti-infective drugs. Curr Eye Res 2005 Jul;30(7):505-15.
- Okamoto T, Tanida T, Wei B, Ueta E, Yamamoto T, Osaki T. Regulation of fungal infection by a combination of amphotericin B and peptide 2, a lactoferrin peptide that activates neutrophils. Clin Diagn Lab Immunol 2004 Nov;11(6):1111-9.
- Mannis MJ. The use of antimicrobial peptides in ophthalmology: an experimental study in corneal preservation and the management of bacterial keratitis. Trans Am Ophthalmol Soc 2002;100:243-71.
- Klotz SA, Penn CC, Negvesky GJ, Butrus SI. Fungal and parasitic infections of the eye. Clin Microbiol Rev 2000 Oct;13(4):662-85.
- Takemura H, Kaku M, Kohno S, Hirakata Y, Tanaka H, Yoshida R, Tomono K, Koga H, Wada A, Hirayama T, Kamihira S. Evaluation of susceptibility of gram-positive and -negative bacteria to human defensins by using radial diffusion assay. Antimicrob Agents Chemother 1996 Oct;40(10):2280-4.
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