Therapeutic Potential of the Antimicrobial Peptide OH-CATH30 for Antibiotic-Resistant Pseudomonas aeruginosa Keratitis

Li, Sheng-An; Liu, Jie; Xiang, Yang; Wang, Yanjie; Lee, Wen-Hui; Zhang, Yun

doi:10.1128/aac.00095-14

Cited by 29 publications

(27 citation statements)

References 29 publications

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“…Li and coworkers [73] reported that OH-CATH30 is protective in keratitis induced by 10 different antibiotic resistant clinical isolates of pseudomonas. Using a rabbit keratitis model they showed OH-CATH30 itself, or as an adjunctive therapy with levofloxacin, reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β), leukocyte infiltration, bacterial load and improved disease.…”

Section: Antimicrobial Peptides (Amps) and Proteinsmentioning

confidence: 99%

“…Using a rabbit keratitis model they showed OH-CATH30 itself, or as an adjunctive therapy with levofloxacin, reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β), leukocyte infiltration, bacterial load and improved disease. OH-CATH30 demonstrates an approximately 6 μg/mL MIC for the P. aeruginosa strains tested [73]. …”

Section: Antimicrobial Peptides (Amps) and Proteinsmentioning

confidence: 99%

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Challenges of corneal infections

Hazlett

Suvas

McClellan

et al. 2016

Expert Review of Ophthalmology

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Introduction Ocular infections remain an important cause of blindness worldwide and represent a challenging public health concern. In this regard, microbial keratitis due to fungal, bacterial, or viral infection can result in significant vision loss secondary to corneal scarring or surface irregularity. Left untreated corneal perforation and endophthalmitis can result, leading to loss of the eye. Rigorously studied animal models of disease pathogenesis have provided novel information that suggests new modes of treatment that may be efficacious clinically and emerging clinical data is supportive of some of these discoveries. Areas covered This review focuses on advances in our understanding of disease pathogenesis in animal models and clinical studies and how these relate to improved clinical treatment. We also discuss a novel approach to treatment of microbial keratitis due to infection with these bacterial pathogens using PACK-CXL and recommend increased basic and clinical studies to address and refine the efficacy of this procedure. Expert commentary Because resistance to antibiotics has developed over time to these bacterial pathogens, caution must be exercised in treatment. Attractive novel modes of treatment that hold new promise for further investigation include lipid based therapy, as well as use of small molecules that bind deleterious specific host responsive molecules and use of microRNA based therapies.

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Section: Antimicrobial Peptides (Amps) and Proteinsmentioning

confidence: 99%

Section: Antimicrobial Peptides (Amps) and Proteinsmentioning

confidence: 99%

Challenges of corneal infections

Hazlett

Suvas

McClellan

et al. 2016

Expert Review of Ophthalmology

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“…An important site of P. aeruginosa infection is the eye, where these organisms are an important cause of keratitis [34, 35]. A major therapeutic strategy against these biofilm infections is the development of optimized antimicrobial peptides delivered topically [36]. There is substantial interest in the development of more active antimicrobial peptides that could be used topically to treat organisms growing at various anatomical sites, whether in a planktonic or biofilm format.…”

Section: P Aeruginosa Resistance To Antimicrobial Peptidesmentioning

confidence: 99%

Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung

Riquelme¹,

Ahn²,

Prince³

2018

J Innate Immun

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Many different species of gram-negative bacteria are associated with infection in the lung, causing exacerbations of chronic obstructive pulmonary disease, cystic fibrosis (CF), and ventilator-associated pneumonias. These airway pathogens must adapt to common host clearance mechanisms that include killing by antimicrobial peptides, antibiotics, oxidative stress, and phagocytosis by leukocytes. Bacterial adaptation to the host is often evident phenotypically, with increased extracellular polysaccharide production characteristic of some biofilm-associated organisms. Given the relatively limited repertoire of bacterial strategies to elude airway defenses, it seems likely that organisms sharing the same ecological niche might also share common strategies to persistently infect the lung. In this review, we will highlight some of the major factors responsible for the adaptation of Pseudomonas aeruginosa to the lung, addressing how growth in biofilms enables persistent infection, relevant to, but not limited to, the pathogenesis of infection in CF. In contrast, we will discuss how carbapenem-resistant Klebsiella pneumoniae evade immune clearance, an organism often associated with ventilator-associated pneumonia and health-care-acquired pneumonias, but not a typical pathogen in CF.

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“…Our previous work demonstrated that OH30 showed a broad antibacterial spectrum against various bacterial. [12][13][14][15] Moreover, it was reported that OH30 lost approximately 80% antibacterial activity against E. coli 25922 after incubation Figures 3 and 5). In full-thickness wound models, the prepared NP showed significantly fast wound healing and nonscarring results in all the tested groups ( Figure 6).…”

Section: Discussionmentioning

confidence: 93%

“…14 OH30 exhibits an improved clinical effect of treating antibiotic-resistant Pseudomonas aeruginosa that induces rabbit keratitis. 15 Importantly, strong direct bactericidal activity and selective regulation of the expression of various chemokines and cytokines of OH30 are demonstrated to be responsible for protecting the animals from lethal sepsis. 16 Other investigations using reptile cathelicidins as the template also reveal that snake elapid cathelicidins can serve as model molecules for the development of antimicrobial drugs.…”

Section: Introductionmentioning

confidence: 99%

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing

Sun¹,

Zhan²,

Zhang³

et al. 2018

IJN

Self Cite

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BackgroundNonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing.PurposeTo overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated.MethodsCMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models.ResultsThe release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines.ConclusionThe prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles.

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Therapeutic Potential of the Antimicrobial Peptide OH-CATH30 for Antibiotic-Resistant Pseudomonas aeruginosa Keratitis

Cited by 29 publications

References 29 publications

Challenges of corneal infections

Challenges of corneal infections

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing

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