<i>Pseudomonas aeruginosa</i>Small Protease (PASP), a Keratitis Virulence Factor

Tang, Aihua; Caballero, Armando R.; Marquart, Mary E.; O’Callaghan, Richard J.

doi:10.1167/iovs.13-11788

Cited by 31 publications

(31 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It would be reasonable to suppose that since P. aeruginosa invaded the deep corneal stromal, phages could not infiltrate there. P. aeruginosa are motile and produce proteolytic enzymes, such as elastase B, alkaline metalloprotease (37), protease IV (38), and P. aeruginosa small protein (39), and have a type III secretion system (40). These enzymes enable P. aeruginosa to rapidly cause keratitis and to invade deep layers.…”

Section: Discussionmentioning

confidence: 99%

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Furusawa

Iwano

Hiyashimizu

et al. 2016

Appl Environ Microbiol

View full text Add to dashboard Cite

Bacterial keratitis of the horse is mainly caused by staphylococci, streptococci, and pseudomonads. Of these bacteria, Pseudomonas aeruginosa sometimes causes rapid corneal corruption and, in some cases, blindness. Antimicrobial resistance can make treatment very difficult. Therefore, new strategies to control bacterial infection are required. A bacteriophage (phage) is a virus that specifically infects and kills bacteria. Since phage often can lyse antibiotic-resistant bacteria because the killing mechanism is different, we examined the use of phage to treat horse bacterial keratitis. We isolated Myoviridae or Podoviridae phages, which together have a broad host range. They adsorb efficiently to host bacteria; more than 80% of the ⌽R18 phage were adsorbed to host cells after 30 s. In our keratitis mouse model, the administration of phage within 3 h also could kill bacteria and suppress keratitis. A phage multiplicity of infection of 100 times the host bacterial number could kill host bacteria effectively. A cocktail of two phages suppressed bacteria in the keratitis model mouse. These data demonstrated that the phages in this study could completely prevent the keratitis caused by P. aeruginosa in a keratitis mouse model. Furthermore, these results suggest that phage may be a more effective prophylaxis for horse keratitis than the current preventive use of antibiotics. Such treatment may reduce the use of antibiotics and therefore antibiotic resistance. Further studies are required to assess phage therapy as a candidate for treatment of horse keratitis. IMPORTANCEAntibiotic-resistant bacteria are emerging all over the world. Bacteriophages have great potential for resolution of this problem. A bacteriophage, or phage, is a virus that infects bacteria specifically. As a novel therapeutic strategy against racehorse keratitis caused by Pseudomonas aeruginosa, we propose the application of phages for treatment. Phages isolated in this work had in vitro effectiveness for a broad range of P. aeruginosa strains. Indeed, a great reduction of bacterial proliferation was shown in phage therapy for mouse models of P. aeruginosa keratitis. Therefore, to reduce antibiotic usage, phage therapy should be investigated and developed further.

show abstract

Section: Discussionmentioning

confidence: 99%

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Furusawa

Iwano

Hiyashimizu

et al. 2016

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…This is in part due to the ease of performing the procedure, but also, while this treatment appears simple, the sterile procedure has to be followed properly. Furthermore, the antibiotic resistance increases [39][40][41][42][43] and the most virulent pathogens can be selected.…”

Section: Infectious Keratitis Following Corneal Crosslinkingmentioning

confidence: 99%

Infectious Keratitis Following Corneal Crosslinking: A Systematic Review of Reported Cases: Management, Visual Outcome, and Treatment Proposed

Abbouda

Abicca

Alió

2014

Seminars in Ophthalmology

View full text Add to dashboard Cite

Only 10 cases of infectious keratitis following corneal crosslinking are published. The most virulent pathogens were Pseudomonas aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S. epidermidis. Two cases of herpes keratitis were described, suggesting the possibility of systemic antiviral prophylaxis before corneal crosslinking treatment. The most common risk factor of infections identified was postoperative incorrect patient behavior.

show abstract

“…44,45 Moreover, protease IV and P. aeruginosa small protease may degrade complement or antimicrobial peptides, and thus escape from host defenses. 46 Lomholt et al 14 reported that many P. aeruginosa keratitis isolates, among the isolates from patients or from the environment, exhibit high elastase and alkaline protease activities. In the present study, we demonstrated a correlation between the clinical severity of P. aeruginosa keratitis and protease/elastase activity.…”

Section: Discussionmentioning

confidence: 99%

Relationship of Virulence Factors and Clinical Features in Keratitis Caused byPseudomonas aeruginosa

Oka

Suzuki

Ishikawa

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. To examine bacterial virulence factors in Pseudomonas aeruginosa isolates from contact lens (CL) wearers and non-CL wearers with P. aeruginosa keratitis, and to investigate relationships between virulence factors and clinical features of keratitis.METHODS. The study involved 25 subjects including 18 CL and 7 non-CL-related P. aeruginosa keratitis patients. Slit-lamp photographs of all subjects were captured, and the focus occupancy ratio (FOR) was defined as the total focus area/entire cornea area, using image processing software. Twenty-five clinical P. aeruginosa isolates from keratitis were assessed for protease production, elastase production, biofilm formation, bacterial swimming and swarming motility, cell surface hydrophobicity, and genes encoding the type III secretion system (TTSS) effectors (ExoU and ExoS). RESULTS.Ring abscess was found in 9 of 18 CL-related P. aeruginosa keratitis cases (CL[þ] ring[þ] group) but not in another 9 cases (CL[þ] ring[À] group). Expression or prevalence of virulence factors in P. aeruginosa isolates from the CL(þ) ring(þ) group, CL(þ) ring(À) group, and CL(À) group were compared. The FOR for CL(þ) ring(þ) or CL(À) was higher than for CL(þ) ring(À) (P < 0.05 and P < 0.01, respectively). The rate of positive swimming motility for CL(þ) ring(þ) or CL(À) was higher than for CL(þ) ring(À) (P < 0.05), whereas the rate of positive swarming motility for CL(þ) ring(þ) was higher than for CL(þ) ring(À) or CL(À) (P < 0.05). Prevalence of an exoSþ/exoU-genotype for CL(þ) ring(þ) or CL(À) was higher than for CL(þ) ring(À) (P < 0.05). In the CL-related group, expression of elastase and swarming motility significantly correlated with FOR.CONCLUSIONS. Swimming motility, swarming motility, and TTSS ExoS could play a major role in the determination of clinical features of P. aeruginosa keratitis.Keywords: Pseudomonas aeruginosa, keratitis, virulence factors, protease, swarming motility K eratitis caused by Pseudomonas aeruginosa can progress rapidly with suppurative infiltration, and can lead to corneal perforation and melt, resulting in the loss of vision. 1Contact lens (CL) wearers are especially susceptible to development of P. aeruginosa keratitis. Ring abscess, which is a ring-shaped accumulation of polymorphonuclear leukocytes surrounding a central corneal lesion, is a well-known hallmark of P. aeruginosa keratitis.2,3 Along with ring abscess, serrated or satellite lesions with keratitis are sometimes found in P. aeruginosa keratitis.4,5 Pseudomonas aeruginosa can show various clinical features, but little is known about factors that determine these clinical features.To understand the mechanism of pathogenesis in keratitis caused by P. aeruginosa, the virulence factors as well as extracellular products, including proteases, 6-8 exotoxin A, 9 and biofilms, 10 have been investigated. Of these factors, proteases, including metalloproteases such as alkaline protease, elastase A, and elastase B, 11 are important in virulence. We recently reported that MucD protease inhibits neu...

show abstract

Pseudomonas aeruginosaSmall Protease (PASP), a Keratitis Virulence Factor

Abstract: PASP is a commonly secreted protease of P. aeruginosa that contributes significantly to the pathogenesis of keratitis.

Cited by 31 publications

References 35 publications

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Infectious Keratitis Following Corneal Crosslinking: A Systematic Review of Reported Cases: Management, Visual Outcome, and Treatment Proposed

Relationship of Virulence Factors and Clinical Features in Keratitis Caused byPseudomonas aeruginosa

Contact Info

Product

Resources

About