Assessment of elastase as a Pseudomonas aeruginosa virulence factor in experimental lung infection in mink

Elsheikh, Laila Elsadig; Kronevi, Tony; Wretlind, Bengt; Abaas, Saleem; Iglewski, Barbara H.

doi:10.1016/0378-1135(87)90090-3

Cited by 16 publications

(11 citation statements)

References 14 publications

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“…Biofilm dispersal cells of strains 18A and PAO1 were also examined for phenotypic traits (elastase and protease production) associated with the ability to establish infection (Elsheikh et al ., ; Jaffar‐Bandjee et al ., ). The 18A WT isolates were not significantly different from the 18A parent for elastase or total protease activity (Fig.…”

Section: Resultsmentioning

confidence: 99%

Biofilm dispersal cells of a cystic fibrosisPseudomonas aeruginosaisolate exhibit variability in functional traits likely to contribute to persistent infection

Woo

Webb

Kirov

et al. 2012

FEMS Immunol Med Microbiol

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Persistent lung infection by Pseudomonas aeruginosa is typically associated with the development of biofilms, the appearance of morphotypic variants and reduction in the expression of acute virulence factors. We have characterised and compared functional traits [carbon substrate utilisation, attachment and biofilm formation, protease and elastase activity, quorum‐sensing (QS)] of the biofilm dispersal populations of a representative P. aeruginosa isolate from a chronically infected cystic fibrosis individual and P. aeruginosa strain PAO1. The dispersal variants of the clinical strain exhibited significantly greater heterogeneity in all of the phenotypes tested. All morphotypic variants from the dispersal population of the clinical strain showed a significant increase in QS signal and elastase production compared to the parental strain. In contrast, isolates from planktonic cultures were phenotypically identical to the inoculum strain, suggesting that the appearance of these variants was biofilm specific. The clinical strain was shown to have a 3.4‐fold higher mutation frequency than PAO1 which corroborated with the increased diversity of dispersal isolates. These data suggest that the development of a chronic infection phenotype can be reversed to recover acute infection isolates and that growth within a biofilm facilitates diversification of P. aeruginosa which is important for ecological adaptation.

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Section: Resultsmentioning

confidence: 99%

Biofilm dispersal cells of a cystic fibrosisPseudomonas aeruginosaisolate exhibit variability in functional traits likely to contribute to persistent infection

Woo

Webb

Kirov

et al. 2012

FEMS Immunol Med Microbiol

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“…We first tested for elastase and pyocyanin production because these virulence determinants play a role in animal lung infection models (Blackwood et al, 1983;Elsheikh et al, 1987). Three of the 18 mutations that affected virulence of FRD1 on alfalfa also produced less elastase than FRD1 (Fig.…”

Section: Characterization Of the Transposon Insertion Mutantsmentioning

confidence: 99%

Virulence determinants from a cystic fibrosis isolate of Pseudomonas aeruginosa include isocitrate lyase

et al. 2008

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Chronic lung infections caused by Pseudomonas aeruginosa are the leading cause of morbidity and mortality for cystic fibrosis (CF) patients. Adaptation of P. aeruginosa to the CF lung results in the loss of acute virulence determinants and appears to activate chronic virulence strategies in this pathogen. In order to identify such strategies, a random transposon mutagenesis was performed and 18 genes that were required for optimal infection of alfalfa seedlings by FRD1, a CF isolate of P. aeruginosa, were recognized. The largest subset of genes (seven of the 18), were associated with central carbon metabolism, including the gene that encodes isocitrate lyase (ICL), aceA. Because FRD1 is avirulent in animal infection models, we constructed an ICL mutant in P. aeruginosa strain PAO1 in order to assess the requirement of ICL in mammalian infection. The PAO1 ICL mutant was less virulent in the rat lung infection model, indicating that ICL is required for the pathogenesis of P. aeruginosa in mammals. Furthermore, FRD1 showed increased ICL activity and expression of an aceA : : lacZ fusion compared to PAO1. We suggest that upregulation of ICL occurred during adaptation of FRD1 to the CF lung and that some of the novel virulence mechanisms employed by FRD1 to infect alfalfa seedlings may be the same mechanisms P. aeruginosa relies upon to persist within human niches.

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“…Hydrogen cyanide is believed to be the primary toxic factor secreted by P. aeruginosa that is responsible for killing Caenorhabditis elegans [29], and has been detected at elevated levels in the infected lungs of patients suffering from CF [30]. Chitinase is expressed at high cell densities and in biofilms and was shown to be able to bind and degrade colloidal chitin [31], while elastase has been shown to cause localized tissue damage [32]. The redox-active pigments phenazines can generate an oxidative stress on the host and are required for “fast killing” of C. elegans [33].…”

Section: Introductionmentioning

confidence: 99%

BdlA, DipA and Induced Dispersion Contribute to Acute Virulence and Chronic Persistence of Pseudomonas aeruginosa

Petrova

et al. 2014

PLoS Pathog

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The human pathogen Pseudomonas aeruginosa is capable of causing both acute and chronic infections. Differences in virulence are attributable to the mode of growth: bacteria growing planktonically cause acute infections, while bacteria growing in matrix-enclosed aggregates known as biofilms are associated with chronic, persistent infections. While the contribution of the planktonic and biofilm modes of growth to virulence is now widely accepted, little is known about the role of dispersion in virulence, the active process by which biofilm bacteria switch back to the planktonic mode of growth. Here, we demonstrate that P. aeruginosa dispersed cells display a virulence phenotype distinct from those of planktonic and biofilm cells. While the highest activity of cytotoxic and degradative enzymes capable of breaking down polymeric matrix components was detected in supernatants of planktonic cells, the enzymatic activity of dispersed cell supernatants was similar to that of biofilm supernatants. Supernatants of non-dispersing ΔbdlA biofilms were characterized by a lack of many of the degradative activities. Expression of genes contributing to the virulence of P. aeruginosa was nearly 30-fold reduced in biofilm cells relative to planktonic cells. Gene expression analysis indicated dispersed cells, while dispersing from a biofilm and returning to the single cell lifestyle, to be distinct from both biofilm and planktonic cells, with virulence transcript levels being reduced up to 150-fold compared to planktonic cells. In contrast, virulence gene transcript levels were significantly increased in non-dispersing ΔbdlA and ΔdipA biofilms compared to wild-type planktonic cells. Despite this, bdlA and dipA inactivation, resulting in an inability to disperse in vitro, correlated with reduced pathogenicity and competitiveness in cross-phylum acute virulence models. In contrast, bdlA inactivation rendered P. aeruginosa more persistent upon chronic colonization of the murine lung, overall indicating that dispersion may contribute to both acute and chronic infections.

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Assessment of elastase as a Pseudomonas aeruginosa virulence factor in experimental lung infection in mink

Cited by 16 publications

References 14 publications

Biofilm dispersal cells of a cystic fibrosisPseudomonas aeruginosaisolate exhibit variability in functional traits likely to contribute to persistent infection

Biofilm dispersal cells of a cystic fibrosisPseudomonas aeruginosaisolate exhibit variability in functional traits likely to contribute to persistent infection

Virulence determinants from a cystic fibrosis isolate of Pseudomonas aeruginosa include isocitrate lyase

BdlA, DipA and Induced Dispersion Contribute to Acute Virulence and Chronic Persistence of Pseudomonas aeruginosa

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