Microbial Keratitis

Keay, Lisa; Edwards, Katie; Naduvilath, Thomas; Taylor, Hugh R.; Snibson, Grant R.; Forde, Kevin; Stapleton, Fiona

doi:10.1016/j.ophtha.2005.08.013

Cited by 360 publications

(123 citation statements)

References 17 publications

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“…Organisms of the periocular microbiota can reach internal ocular tissues after trauma caused by different conditions. For corneal infections, the most important predisposing risk factors include contact lens wear, surgical and nonsurgical trauma, and the presence of inflammatory ocular surface diseases (4,5). Organisms that are part of the ocular surface microbiota can access the anterior chamber and vitreous cavity following a breach due to intraocular procedures such as cataract, glaucoma, and other surgeries, intravitreal injections, and trauma caused by plant matter and other objects.…”

Section: Discussionmentioning

confidence: 99%

“…Although found as a common constituent of the ocular surface microbiota (1), S. epidermidis is the leading cause of bacterial endophthalmitis following trauma and intraocular procedures (2,3) and has been frequently associated with infectious keratitis worldwide in patients with predisposing risk factors, including contact lens wear, trauma, surgery, and ocular surface inflammatory diseases (4,5). The success of S. epidermidis as a pathogen is particularly attributed to its capability to form agglomerations of cells embedded in and protected by an extracellular matrix composed of polysaccharides and/or proteins, known as biofilm, which confers resistance to antibiotic action and host immune defenses (6).…”

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confidence: 99%

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Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates Belonging Predominantly to Clonal Complex 2 Subcluster II

2014

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Staphylococcus epidermidis is an abundant member of the microbiota of the human skin and wet mucosa, which is commonly associated with sight-threatening infections in eyes with predisposing factors. Ocular S. epidermidis has become notorious because of its capability to form biofilms on different ocular devices and due to the evolving rates of antimicrobial resistance. In this study, the molecular epidemiology of 30 ocular methicillin-resistant S. epidermidis (MRSE) isolates was assessed using multilocus sequence typing (MLST). Antimicrobial resistance, accessory gene-regulator and staphylococcal cassette chromosome mec (SCCmec) types, biofilm formation, and the occurrence of biofilm-associated genes were correlated with MLST clonal complexes. Sequence types (STs) frequently found in the hospital setting were rarely found in our collection. Overall, 12 different STs were detected with a predominance of ST59 (30%), ST5 and ST6 (13.3% each). Most of the isolates (93.3%) belonged to the clonal complex 2 (CC2) and grouped mainly within subcluster CC2-II (92.9%). Isolates grouped within this subcluster were frequently biofilm producers (92.3%) with a higher occurrence of the aap (84.5%) and bhp (46.1%) genes compared to icaA (19.2%). SCCmec type IV (53.8%) was predominant within CC2-II strains, while 38.4% were nontypeable. In addition, CC2-II strains were frequently multidrug resistant (80.7%) and demonstrated to be particularly resistant to ciprofloxacin (80.8%), ofloxacin (77%), azithromycin (61.5%), and gentamicin (57.7%). Our findings demonstrate the predominance of a particular MRSE cluster causing ocular infections, which was associated with high rates of antimicrobial resistance and particularly the carriage of biofilm-related genes coding for proteinaceous factors implicated in biofilm accumulation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates Belonging Predominantly to Clonal Complex 2 Subcluster II

2014

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“…In our hospital, the most common indications for enucleation and evisceration in this age group were nonresolving severe keratitis (30 patients, 64%) and corneal perforation (17 patients 36%). The variables found to be associated with adverse outcomes in cases of microbial keratitis in the past include severe infection [12][13][14][15], advanced patient age [13,16,17], poor visual acuity at presentation [13,15,17], associated herpetic keratitis [14,18], ocular surface disease [12], associated systemic disease [12], prior treatment with steroids [19], and a delay in seeking treatment [20]. Failure to use fortified antibiotics has also been found to be associated with poor prognosis in cases with microbial keratitis [20].…”

Section: Discussionmentioning

confidence: 99%

Clinical review of corneal ulcers resulting in evisceration and enucleation in elderly population

Constantinou

Jhanji

Tao

et al. 2009

Graefes Arch Clin Exp Ophthalmol

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“…icrobial keratitis (MK) is a blinding disease with poor visual outcomes even with effective antibiotics and antifungal agents (1)(2)(3). In addition to being a major cause of hospital-acquired infections, such as ventilator-associated pneumonia (4,5), Serratia marcescens is a common cause of MK (1,2,(6)(7)(8), yet the virulence factors involved in this process are poorly understood.…”

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confidence: 99%

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

et al. 2015

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The Gram-negative bacterium and opportunistic pathogen Serratia marcescens causes ocular infections in healthy individuals. Secreted protease activity was characterized from 44 ocular clinical isolates, and a higher frequency of protease-positive strains was observed among keratitis isolates than among conjunctivitis isolates. A positive correlation between protease activity and cytotoxicity to human corneal epithelial cells in vitro was determined. Deletion of prtS in clinical keratitis isolate K904 reduced, but did not eliminate, cytotoxicity and secreted protease production. This indicated that PrtS is necessary for full cytotoxicity to ocular cells and implied the existence of another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the S. marcescens Db11 genome revealed three additional open reading frames predicted to code for serralysin-like proteases noted here as slpB, slpC, and slpD. Induced expression of prtS and slpB, but not slpC and slpD, in strain PIC3611 rendered the strain cytotoxic to a lung carcinoma cell line; however, only prtS induction was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion of both prtS and slpB genes was defective in secreted protease activity and cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI-inhibited protease activity and cytotoxicity to airway and ocular cell lines in vitro. Lastly, genetic analysis indicated that the type I secretion system gene, lipD, is required for SlpB secretion. These genetic data introduce SlpB as a new cytotoxic protease from S. marcescens. Microbial keratitis (MK) is a blinding disease with poor visual outcomes even with effective antibiotics and antifungal agents (1-3). In addition to being a major cause of hospital-acquired infections, such as ventilator-associated pneumonia (4, 5), Serratia marcescens is a common cause of MK (1, 2, 6-8), yet the virulence factors involved in this process are poorly understood. In general, bacterial secreted factors, including hemolysins and proteases, contribute to the pathogenesis of bacterial corneal infections (9-12). There are several studies characterizing the importance of proteases from S. marcescens isolates in ocular infections, most recently reviewed by Matsumoto (13). Serralysin is a cytotoxic factor capable of killing mammalian cells in vitro (14,15). Purified serralysin is sufficient to cause keratitis when injected into rabbit eyes and promotes the spread of bacteria through the corneal stroma (16-18). Additionally, serralysin can degrade components of the human immune system, such as PAR-2, in vitro, and this may impact corneal pathogenesis (13,(19)(20)(21). Serralysin, and serralysin family metalloproteases, such as alkaline protease from Pseudomonas aeruginosa, can proteolyze mammalian cell surface proteins, thereby modulating cell physiology. A recent example is the protease-mediated activation of the epithelial sodium channel, lea...

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Microbial Keratitis

Cited by 360 publications

References 17 publications

Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates Belonging Predominantly to Clonal Complex 2 Subcluster II

Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates Belonging Predominantly to Clonal Complex 2 Subcluster II

Clinical review of corneal ulcers resulting in evisceration and enucleation in elderly population

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

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