Association Between Cultures of Contact Lens and Corneal Scraping in Contact Lens–Related Microbial Keratitis

Das, Sujata

doi:10.1001/archopht.125.9.1182

Cited by 67 publications

(41 citation statements)

References 34 publications

(32 reference statements)

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“…In this study, we tested a much larger number of ocular isolates from the three major eye infections caused by S. marcescens: conjunctivitis, endophthalmitis, and keratitis. S. marcescens is most prevalent as an agent of keratitis, with many studies listing it as the second most common cause of contact lens-associated keratitis, behind P. aeruginosa (2,6,(53)(54)(55)(56). S. marcescens is associated with common contact lens-associated inflammation complications (57) and activates inflammation through both the TLR4/MD-2/MyD88 and MyD-88/IL-1R1 pathways (58).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

et al. 2015

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“…Paradoxically, in cases of contact lens-related microbial keratitis in which the corneal scraping is culture negative, contact lens culture may sometimes be a clue to the possible organism involved (7). This may also explain the superior results obtained by some authors when culturing corneal biopsy specimens compared to those obtained from culturing corneal scrapings (23).…”

Section: Case Reportmentioning

confidence: 99%

Uncommon Neosartorya udagawae Fungus as a Causative Agent of Severe Corneal Infection

Posteraro

Mattei²,

Trivella³

et al. 2011

J Clin Microbiol

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We report the first documented case of a posttraumatic fungal keratitis caused by Neosartorya udagawae. The patient was empirically treated with fluconazole until a corneal scraping grew an Aspergillus fumigatus-like fungus, and itraconazole therapy was then established. A sequence-based approach assigned the isolate to the species. Five months after completion of antifungal therapy, endophthalmitis occurred and orbital exenteration was necessary.

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“…It is an important opportunistic pathogen in hospitals (6)(7)(8)(9), and isolates collected in intensive care units became more resistant to antibiotics between 2004 and 2009 (10). S. marcescens is also a leading contaminant of contact lens cases and contact lenses and can cause vision-threatening microbial keratitis and other ocular infections (11)(12)(13). S. marcescens synthesizes several secreted enzymes, including proteases, a potent nuclease, chitinases, and other enzymes that have been used for biotechnological applications or have been implicated in cytotoxicity to mammalian cells and pathogenesis (14)(15)(16).…”

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confidence: 99%

EepR Mediates Secreted-Protein Production, Desiccation Survival, and Proliferation in a Corneal Infection Model

et al. 2015

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Serratia marcescens is a soil-and water-derived bacterium that secretes several host-directed factors and causes hospital infections and community-acquired ocular infections. The putative two-component regulatory system composed of EepR and EepS regulates hemolysis and swarming motility through transcriptional control of the swrW gene and pigment production through control of the pigA-pigN operon. Here, we identify and characterize a role for EepR in regulation of exoenzyme production, stress survival, cytotoxicity to human epithelial cells, and virulence. Genetic analysis supports the model that EepR is in a common pathway with the widely conserved cyclic-AMP receptor protein that regulates protease production. Together, these data introduce a novel regulator of host-pathogen interactions and secreted-protein production. Secreted enzymes such as proteases can act as immune system and physiology modulators and virulence factors during infection by a wide variety of pathogens (1-5). Serratia marcescens is a Gram-negative coccobacillus bacterium isolated from a variety of environmental niches and the human gut. It is an important opportunistic pathogen in hospitals (6-9), and isolates collected in intensive care units became more resistant to antibiotics between 2004 and 2009 (10). S. marcescens is also a leading contaminant of contact lens cases and contact lenses and can cause vision-threatening microbial keratitis and other ocular infections (11-13). S. marcescens synthesizes several secreted enzymes, including proteases, a potent nuclease, chitinases, and other enzymes that have been used for biotechnological applications or have been implicated in cytotoxicity to mammalian cells and pathogenesis (14-16). However, the regulation of these enzymes is poorly understood.Known regulators of S. marcescens proteolysis include the crp gene that encodes the cyclic-AMP (cAMP) receptor protein CRP. Mutation of crp yields bacteria with elevated production of the protease serralysin (PrtS; also known as PrtA) and a loss of secreted-chitinase and -lipase activities (17). Matsuyama and colleagues observed reduced expression of extracellular protease activity when the hexS gene, an lhrA homolog, was expressed from a multicopy plasmid, suggesting a negative regulatory role for this protein (63).Extracellular proteases, such as the S. marcescens PrtS metalloprotease, are considered important virulence factors. In vitro studies indicate that serralysin is cytotoxic to a variety of cell types (16,21,22). PrtS contributed to tissue damage in corneal infections using a rabbit model (23), altered immune cell interactions using a silkworm model (20,24), and enhanced secondary infections by a respiratory virus in mice (25). Those studies provided the impetus to determine regulators of S. marcescens protease production.A putative regulatory system that includes the response regulator-like protein EepR and a putative hybrid-histidine kinase, EepS, was recently identified for its role in controlling expression of swarming motility, pigme...

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Association Between Cultures of Contact Lens and Corneal Scraping in Contact Lens–Related Microbial Keratitis

Cited by 67 publications

References 34 publications

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

Uncommon Neosartorya udagawae Fungus as a Causative Agent of Severe Corneal Infection

EepR Mediates Secreted-Protein Production, Desiccation Survival, and Proliferation in a Corneal Infection Model

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