Understanding clinical and immunological features associated with Pseudomonas and Staphylococcus keratitis

Vijay, Ajay Kumar; Stapleton, Fiona; Henriquez, Fiona L.; Carnt, Nicole

doi:10.1016/j.clae.2020.11.014

Cited by 20 publications

(16 citation statements)

References 125 publications

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“…Dysfunctional inflammation plays an important role during bacterial infections, which will cause host-induced inflammatory damage and vision loss during bacterial infection if it remains uncontrolled. Researchers find that during the early stage of bacterial infection in mice, neutrophils recruit to the site of infection from perilimbal circulation, foreshadowing the pathophysiology of acute-stage bacterial keratitis [ 69 ]. S. aureus 8325−4 is an α-toxin-positive parent strain, as α-toxin is deemed to be a virulence factor in some animal infection models and is significant for infections that disrupt epithelial barriers in the cornea.…”

Section: Cornea and Ocular Surfacementioning

confidence: 99%

“…S. aureus 8325−4 is an α-toxin-positive parent strain, as α-toxin is deemed to be a virulence factor in some animal infection models and is significant for infections that disrupt epithelial barriers in the cornea. In the end, epithelial cell lysis led to underlying stroma exposure and increased neutrophil density [ 69 ]. β-toxin is a type of sphingomyelinase and is toxic to plenty of cells, such as fibroblasts, leukocytes, and macrophages.…”

Section: Cornea and Ocular Surfacementioning

confidence: 99%

See 1 more Smart Citation

Neutrophil Extracellular Traps (NETs) in Ocular Diseases: An Update

Zeng

Zhou

et al. 2022

Biomolecules

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Neutrophil extracellular traps (NETs) are net-like complexes expelled from neutrophils, composing cell-free deoxyribonucleic acid (DNA), histones, and neutrophil granule proteins. Besides capturing and eliminating pathogens, NETs also exacerbate the inflammatory response associated with various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Currently, there are growing reports about NETs involved in the pathogenesis of ocular diseases. This review primarily focuses on the pathogenesis of NETs in the ophthalmology field, highlighting their importance in serving as potential targets for the therapy of ocular diseases.

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Section: Cornea and Ocular Surfacementioning

confidence: 99%

Section: Cornea and Ocular Surfacementioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) in Ocular Diseases: An Update

Zeng

Zhou

et al. 2022

Biomolecules

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“…The clinical findings of bacterial corneal ulcer depend on the type of infecting bacterium [28,62], in part because of differences in the virulence factors and enzymes released by the bacterial cells [30]. Pseudomonas aeruginosa and S. aureus are the most common bacteria isolated from infectious corneal ulcer [20].…”

Section: Direct Collagen Destruction By Factors Released From Bacteriamentioning

confidence: 99%

“…Excellent reviews on the epidemiology, bacteriology, and clinical treatment of infectious keratitis have been published [19,20,[29][30][31][32][33]. In this review article, we address the role of corneal fibroblasts in the metabolism of collagen in the corneal stroma, how bacterial invasion disrupts this homeostatic role, and potential new directions for the development of novel therapies for corneal ulceration [34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis

Nishida

Sugioka

Fukuda

et al. 2021

IJMS

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The shape and transparency of the cornea are essential for clear vision. However, its location at the ocular surface renders the cornea vulnerable to pathogenic microorganisms in the external environment. Pseudomonas aeruginosa and Staphylococcus aureus are two such microorganisms and are responsible for most cases of bacterial keratitis. The development of antimicrobial agents has allowed the successful treatment of bacterial keratitis if the infection is diagnosed promptly. However, no effective medical treatment is available after progression to corneal ulcer, which is characterized by excessive degradation of collagen in the corneal stroma and can lead to corneal perforation and corneal blindness. This collagen degradation is mediated by both infecting bacteria and corneal fibroblasts themselves, with a urokinase-type plasminogen activator (uPA)-plasmin-matrix metalloproteinase (MMP) cascade playing a central role in collagen destruction by the host cells. Bacterial factors stimulate the production by corneal fibroblasts of both uPA and pro-MMPs, released uPA mediates the conversion of plasminogen in the extracellular environment to plasmin, and plasmin mediates the conversion of secreted pro-MMPs to the active form of these enzymes, which then degrade stromal collagen. Bacterial factors also stimulate expression by corneal fibroblasts of the chemokine interleukin-8 and the adhesion molecule ICAM-1, both of which contribute to recruitment and activation of polymorphonuclear neutrophils, and these cells then further stimulate corneal fibroblasts via the secretion of interleukin-1. At this stage of the disease, bacteria are no longer necessary for collagen degradation. In this review, we discuss the pivotal role of corneal fibroblasts in corneal ulcer associated with infection by P. aeruginosa or S. aureus as well as the development of potential new modes of treatment for this condition.

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“…Representation of human body site infections and main clinical manifestations of P. aeruginosa. Healthcare-associated infections highlighted in blue illustrate the significant burden of P. aeruginosa on invasive acts, surgery, and device use, resulting in local or systemic complications ( Wu et al., 2011 ; Dando et al., 2014 ; Gahlot et al., 2014 ; Elborn, 2016 ; Durand, 2017 ; Newman et al., 2017 ; Arsovic et al., 2020 ; Ramireddy et al., 2020 ; Chai and Xu, 2020 ; Shukla et al., 2020 ; Jean et al., 2020 ; Montravers et al., 2020 ; Cerioli et al., 2020 ; Shrestha et al., 2021 ; Vieira et al., 2016 ; Hauser and Ozer, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

What Is New in the Anti–Pseudomonas aeruginosa Clinical Development Pipeline Since the 2017 WHO Alert?

Reig

Gouëllec

Bleves

2022

Front. Cell. Infect. Microbiol.

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The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are considered “critical-priority” bacteria by the World Health Organization (WHO) since 2017 taking into account criteria such as patient mortality, global burden disease, and worldwide trend of multi-drug resistance (MDR). Indeed P. aeruginosa can be particularly difficult to eliminate from patients due to its combinatory antibiotic resistance, multifactorial virulence, and ability to over-adapt in a dynamic way. Research is active, but the course to a validated efficacy of a new treatment is still long and uncertain. What is new in the anti–P. aeruginosa clinical development pipeline since the 2017 WHO alert? This review focuses on new solutions for P. aeruginosa infections that are in active clinical development, i.e., currently being tested in humans and may be approved for patients in the coming years. Among 18 drugs of interest in December 2021 anti–P. aeruginosa development pipeline described here, only one new combination of β-lactam/β-lactamase inhibitor is in phase III trial. Derivatives of existing antibiotics considered as “traditional agents” are over-represented. Diverse “non-traditional agents” including bacteriophages, iron mimetic/chelator, and anti-virulence factors are significantly represented but unfortunately still in early clinical stages. Despite decade of efforts, there is no vaccine currently in clinical development to prevent P. aeruginosa infections. Studying pipeline anti–P. aeruginosa since 2017 up to now shows how to provide a new treatment for patients can be a difficult task. Given the process duration, the clinical pipeline remains unsatisfactory leading best case to the approval of new antibacterial drugs that treat CRPA in several years. Beyond investment needed to build a robust pipeline, the Community needs to reinvent medicine with new strategies of development to avoid the disaster. Among “non-traditional agents”, anti-virulence strategy may have the potential through novel and non-killing modes of action to reduce the selective pressure responsible of MDR.

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Understanding clinical and immunological features associated with Pseudomonas and Staphylococcus keratitis

Cited by 20 publications

References 125 publications

Neutrophil Extracellular Traps (NETs) in Ocular Diseases: An Update

Neutrophil Extracellular Traps (NETs) in Ocular Diseases: An Update

Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis

What Is New in the Anti–Pseudomonas aeruginosa Clinical Development Pipeline Since the 2017 WHO Alert?

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