Identification of a Novel Secreted Protease from<i>Pseudomonas aeruginosa</i>that Causes Corneal Erosions

Marquart, Mary E.; Caballero, Armando R.; Chomnawang, Mullika Traidej; Thibodeaux, Brett A.; Twining, Sally S.; O’Callaghan, Richard J.

doi:10.1167/iovs.04-1483

Cited by 75 publications

(73 citation statements)

References 51 publications

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“…As previously reported by Purschke et al (2012), we observed a significant increase in the production of iron-regulated proteases by P. aeruginosa in coculture supernatants, including PrpL, PasP, AprA and a hypothetical protein zinc-protease, PA0572 (Supplementary Table S3) (Wilderman et al, 2001;Marquart et al, 2005). These proteins are known for their strong proteolytic activities, which are responsible for rupturing tight junctions in the epithelium, leading to tissue invasion and bacterial spreading (Azghani et al, 1993).…”

Section: Interspecies Competition Triggers Virulencesupporting

confidence: 78%

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

et al. 2014

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Inter-kingdom and interspecies interactions are ubiquitous in nature and are important for the survival of species and ecological balance. The investigation of microbe-microbe interactions is essential for understanding the in vivo activities of commensal and pathogenic microorganisms. Candida albicans, a polymorphic fungus, and Pseudomonas aeruginosa, a Gram-negative bacterium, are two opportunistic pathogens that interact in various polymicrobial infections in humans. To determine how P. aeruginosa affects the physiology of C. albicans and vice versa, we compared the proteomes of each species in mixed biofilms versus single-species biofilms. In addition, extracellular proteins were analyzed. We observed that, in mixed biofilms, both species showed differential expression of virulence proteins, multidrug resistance-associated proteins, proteases and cell defense, stress and iron-regulated proteins. Furthermore, in mixed biofilms, both species displayed an increase in mutability compared with monospecific biofilms. This characteristic was correlated with the downregulation of enzymes conferring protection against DNA oxidation. In mixed biofilms, P. aeruginosa regulates its production of various molecules involved in quorum sensing and induces the production of virulence factors (pyoverdine, rhamnolipids and pyocyanin), which are major contributors to the ability of this bacterium to cause disease. Overall, our results indicate that interspecies competition between these opportunistic pathogens enhances the production of virulence factors and increases mutability and thus can alter the course of hostpathogen interactions in polymicrobial infections.

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Section: Interspecies Competition Triggers Virulencesupporting

confidence: 78%

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

et al. 2014

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“…aeruginosa is capable of secreting at least 7 different proteases including elastase A and B, modified elastase, alkaline protease, protease IV, P. aeruginosa small protease and large exoprotease, some of which play a potential role in the pathogenesis of keratitis [113,202]. Metalloproteases especially elastase B (Las B) and alkaline protease (AP), play a considerable role in keratitis as Las B injection into the corneal stroma result in significant corneal damage [73,88].…”

Section: Bacterial Invasion and Cytotoxic Effectsmentioning

confidence: 99%

Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

157

121

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Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field.

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“…Other protease bands were either weak or not visible in the low-proteaseproducing strains and the gelatinolytic band in lane 5 (Fig. 4) with an apparent molecular mass of~80 kDa was most likely PASP (Marquart et al, 2005). Protease IV activities in P. aeruginosa culture supernatants were determined (Table 2).…”

Section: Detection Of Protease IV In Clinical Isolatesmentioning

confidence: 99%

“…The virulence factors most commonly associated with P. aeruginosa-induced ocular damage are exo-enzymes S (exoS) and U (exoU) (Fleiszig et al, 1997), elastase (lasB) (Kessler & Blumberg, 1987), alkaline protease (aprA) (Twining et al, 1993) and protease IV (piv) (O'Callaghan et al, 1996). Another protease, P. aeruginosa small protease (PASP), can also cause rapid corneal damage (Marquart et al, 2005). Other important pathogenic mechanisms include the genes involved in translocation and activation of virulence proteins via the type II (xcp) and type III secretory pathways (Sandkvist, 2001;Yahr et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Characterization of protease IV expression in Pseudomonas aeruginosa clinical isolates

Conibear

Willcox

Flanagan

et al. 2012

Journal of Medical Microbiology

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Expression of protease IV by Pseudomonas aeruginosa during ocular infections contributes significantly to tissue damage. However, several P. aeruginosa strains isolated from ocular infections or inflammatory events produce very low levels of protease IV. The aim of the present study was to characterize, genetically and phenotypically, the presence and expression of the protease IV gene in a group of clinical isolates that cause adverse ocular events of varying degrees, and to elucidate the possible control mechanisms of expression associated with this virulence factor. Protease IV gene sequences from seven clinical isolates of P. aeruginosa were determined and compared to P. aeruginosa strains PAO1 and PA103-29. Production and enzyme activity of protease IV were measured in test strains and compared to that of quorumsensing gene (lasRI) mutants and the expression of other virulence factors. Protease IV gene sequence similarities between the isolates were 97.5-99.5 %. The strains were classified into two distinct phylogenetic groups that correlated with the presence of exo-enzymes from type three secretion systems (TTSS). Protease IV concentrations produced by PAODlasRI mutants and the two clinical isolates with a lasRI gene deficiency were restored to levels comparable to strain PAO1 following complementation of the quorum-sensing gene deficiencies. The protease IV gene is highly conserved in P. aeruginosa clinical isolates that cause a range of adverse ocular events. Observed variations within the gene sequence appear to correlate with presence of specific TTSS genes. Protease IV expression was shown to be regulated by the Las quorum-sensing system. INTRODUCTIONInflammation and infection in the cornea (keratitis) arising from Pseudomonas aeruginosa infection can lead rapidly to scarring and loss of sight unless prompt and targeted treatment is initiated (Sankaridurg et al., 2000). P. aeruginosa virulence is attributed, in part, to the production of several destructive proteins and stimulation of host immune response in the ocular tissues (Hazlett, 2002). The virulence factors most commonly associated with P. aeruginosa-induced ocular damage are exo-enzymes S (exoS) and U (exoU) (Fleiszig et al., 1997), elastase (lasB) (Kessler & Blumberg, 1987), alkaline protease (aprA) (Twining et al., 1993) and protease IV (piv) (O'Callaghan et al., 1996). Another protease, P. aeruginosa small protease (PASP), can also cause rapid corneal damage (Marquart et al., 2005). Other important pathogenic mechanisms include the genes involved in translocation and activation of virulence proteins via the type II (xcp) and type III secretory pathways (Sandkvist, 2001;Yahr et al., 1997).Protease IV is a lysine-specific endoprotease and a significant virulence factor for pathogenesis of P. aeruginosa in the eye and lung (Caballero et al., 2004; Engel et al., 1997;Wilderman et al., 2001). Mature protease IV degrades important host immunological proteins such as complement and IgG (Engel et al., 1998). Protease IV also compromises the inte...

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Identification of a Novel Secreted Protease fromPseudomonas aeruginosathat Causes Corneal Erosions

Abstract: PASP is a protease that has not been previously identified. It causes corneal epithelial erosions, indicating its likely activity as a virulence-promoting factor in Pseudomonas keratitis.

Cited by 75 publications

References 51 publications

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

Pathogenesis of microbial keratitis

Characterization of protease IV expression in Pseudomonas aeruginosa clinical isolates

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