In Vitro Activity of Human β-Defensin 2 against<i>Pseudomonas aeruginosa</i>in the Presence of Tear Fluid

Li-min, Huang; Redfern, Rachel L.; Narayanan, Srihari; Reins, Rose Y.; McDermott, Alison M.

doi:10.1128/aac.01317-06

Cited by 42 publications

(59 citation statements)

References 67 publications

(76 reference statements)

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“…Thus, it remains possible that the role of AMPs in protection against P. aeruginosa traversal in vitro also involves Our data demonstrated a role for mBD-3, a murine ortholog of hBD-2, in clearing bacteria from the healthy mouse eye in vivo. This is of interest considering that tear fluid has been shown to interfere with the antimicrobial function of its ortholog hBD-2 albeit in vitro (22). In a previous study, we found that SP-D can also contribute to bacterial clearance from the healthy ocular surface (43), yet it has weak antimicrobial activity against the strains tested.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we found that SP-D can also contribute to bacterial clearance from the healthy ocular surface (43), yet it has weak antimicrobial activity against the strains tested. However, it is likely that many factors involved in clearance at the ocular surface work additively or synergistically to increase their antimicrobial activity against P. aeruginosa (22,55), thereby also countering the negative impact of potential modulators such as tear fluid.…”

Section: Discussionmentioning

confidence: 99%

“…Since AMPs can have broad-spectrum antimicrobial activity, which includes activity against P. aeruginosa (14,22,37,42), it is likely that at least part of the mechanism for AMP protection against P. aeruginosa traversal involves the killing of bacteria in the in vitro assays. Indeed, the data showed increased bacterial viability at the apical site of inoculation after AMP knockdown in vitro and knockout in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…While we were unable to prove directly that mBD-3 protects mouse corneas against bacterial traversal, other data did show that it participates in maintaining ocular surface resistance to bacteria during health, i.e., in clearing bacteria from the healthy ocular surface and protecting the corneal epithelium against bacterial adherence, even when experiments were done ex vivo to compensate for differences in clearance. The mechanism for these protective roles in vivo could involve the killing of approaching bacterial cells (22), but effects on the epithelial cell expression of other antimicrobial/ antiadherence factors, or even on resident dendritic cells of the cornea, cannot be ruled out. In summary, the capacity to cross the epithelial cell multilayers is likely to be a critical virulence strategy for both opportunistic and outright pathogens that infect body surfaces in the absence of overt tissue injury.…”

Section: Vol 79 2011mentioning

confidence: 99%

“…This was done because some tear fluid AMPs could impact bacterial viability or the ability to adhere/traverse. This also served to exclude known effects of tear fluid on AMP efficacy (22). mBD-3 (a murine ortholog of hBD-2) was chosen for study given its recently reported contributions to the resolution of P. aeruginosa corneal infections established by scratch injury (56).…”

Section: P Aeruginosa Traverses Telomerase-immortalized Multilayeredmentioning

confidence: 99%

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Role of Defensins in Corneal Epithelial Barrier Function against Pseudomonas aeruginosa Traversal

et al. 2011

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Studies have shown that epithelium-expressed antimicrobial peptides (AMPs), e.g., ␤-defensins, play a role in clearing bacteria from mouse corneas already infected with Pseudomonas aeruginosa. Less is known about the role of AMPs in allowing the cornea to resist infection when healthy. We previously reported that contact lens exposure, a major cause of P. aeruginosa keratitis, can inhibit the upregulation of human ␤-defensin 2 (hBD-2) by corneal epithelial cells in response to P. aeruginosa antigens in vitro. Here, we studied the role of AMPs in maintaining the corneal epithelial barrier to P. aeruginosa penetration using both in vitro (human) and in vivo (mouse) experiments. Results showed that preexposing human corneal epithelial multilayers to bacterial antigens in a culture supernatant (known to upregulate AMP expression) reduced epithelial susceptibility to P. aeruginosa traversal up to 6-fold (P < 0.001). Accordingly, small interfering RNA (siRNA) knockdown of any one of four AMPs expressed by human epithelia promoted P. aeruginosa traversal by more than 3-fold (P < 0.001). The combination knockdown of AMPs further enhanced susceptibility to bacterial traversal by ϳ8-fold (P < 0.001). In vivo experiments showed that the loss of murine ␤-defensin 3 (mBD-3), a murine ortholog of hBD-2, enhanced corneal susceptibility to P. aeruginosa. The uninjured ocular surface of mBD-3 ؊/؊ mice showed a reduced capacity to clear P. aeruginosa, and their corneal epithelia were more susceptible to bacterial colonization, even when inoculated ex vivo to exclude tear fluid effects. Together, these in vitro and in vivo data show functional roles for AMPs in normal corneal epithelial cell barrier function against P. aeruginosa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Vol 79 2011mentioning

confidence: 99%

Section: P Aeruginosa Traverses Telomerase-immortalized Multilayeredmentioning

confidence: 99%

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Role of Defensins in Corneal Epithelial Barrier Function against Pseudomonas aeruginosa Traversal

et al. 2011

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Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

Bastos

Trindade

Costa

et al. 2017

Medicinal Research Reviews

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Antimicrobial peptides (AMPs) are an integral part of the innate immune defense mechanism of many organisms. Due to the alarming increase of resistance to antimicrobial therapeutics, a growing interest in alternative antimicrobial agents has led to the exploitation of AMPs, both synthetic and isolated from natural sources. Thus, many peptide-based drugs have been the focus of increasing attention by many researchers not only in identifying novel AMPs, but in defining mechanisms of antimicrobial peptide activity as well. Herein, we review the available strategies for the identification of AMPs in human body fluids and their mechanism(s) of action. In addition, an overview of the distribution of AMPs across different human body fluids is provided, as well as its relation with microorganisms and infectious conditions.

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The antimicrobial peptide database is 20 years old: Recent developments and future directions

Wang

2023

Protein Science

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In 2023, the Antimicrobial Peptide Database (currently available at https://aps.unmc.edu) is 20‐years‐old. The timeline for the APD expansion in peptide entries, classification methods, search functions, post‐translational modifications, binding targets, and mechanisms of action of antimicrobial peptides (AMPs) has been summarized in our previous Protein Science paper. This article highlights new database additions and findings. To facilitate antimicrobial development to combat drug‐resistant pathogens, the APD has been re‐annotating the data for antibacterial activity (active, inactive, and uncertain), toxicity (hemolytic and nonhemolytic AMPs), and salt tolerance (salt sensitive and insensitive). Comparison of the respective desired and undesired AMP groups produces new knowledge for peptide design. Our unification of AMPs from the six life kingdoms into “natural AMPs” enabled the first comparison with globular or transmembrane proteins. Due to the dominance of amphipathic helical and disulfide‐linked peptides, cysteine, glycine, and lysine in natural AMPs are much more abundant than those in globular proteins. To include peptides predicted by machine learning, a new “predicted” group has been created. Remarkably, the averaged amino acid composition of predicted peptides is located between the lower bound of natural AMPs and the upper bound of synthetic peptides. Synthetic peptides in the current APD, with the highest cationic and hydrophobic amino acid percentages, are mostly designed with varying degrees of optimization. Hence, natural AMPs accumulated in the APD over 20 years have laid the foundation for machine learning prediction. We discuss future directions for peptide discovery. It is anticipated that the APD will continue to play a role in research and education.

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In Vitro Activity of Human β-Defensin 2 againstPseudomonas aeruginosain the Presence of Tear Fluid

Cited by 42 publications

References 67 publications

Role of Defensins in Corneal Epithelial Barrier Function against Pseudomonas aeruginosa Traversal

Role of Defensins in Corneal Epithelial Barrier Function against Pseudomonas aeruginosa Traversal

Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

The antimicrobial peptide database is 20 years old: Recent developments and future directions

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