Pore-forming Staphylococcus aureus ?-toxin triggers epidermal growth factor receptor-dependent proliferation

Haugwitz, Ulrike; Bobkiewicz, Wiesia; Han, Shan-Rui; Beckmann, Erik; Veerachato, Gunnaporn; Shaid, Shabnam; Biehl, Saskia; Dersch, Katrin; Bhakdi, Sucharit; Husmann, Matthias

doi:10.1111/j.1462-5822.2006.00733.x

Cited by 55 publications

(53 citation statements)

References 41 publications

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“…After 24 h, the medium was replaced with diluted ECP (400 g/ml) or medium controls and the plates were incubated for 90 min. The total amount of ATP in cell lysates was measured luminometrically using a firefly luciferase-based assay as described elsewhere (41).…”

Section: Methodsmentioning

confidence: 99%

Chromosome-Encoded Hemolysin, Phospholipase, and Collagenase in Plasmidless Isolates of Photobacterium damselae subsp. damselae Contribute to Virulence for Fish

Vences

Rivas

Lemos

et al. 2017

Appl Environ Microbiol

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Photobacterium damselae subsp. damselae is a pathogen of marine animals, including fish of importance in aquaculture. The virulence plasmid pPHDD1, characteristic of highly hemolytic isolates, encodes the hemolysins damselysin (Dly) and phobalysin (PhlyP). Strains lacking pPHDD1 constitute the vast majority of the isolates from fish outbreaks, but genetic studies to identify virulence factors in plasmidless strains are scarce. Here, we show that the chromosome I-encoded hemolysin PhlyC plays roles in virulence and cell toxicity in pPHDD1-negative isolates of this pathogen. By combining the analyses of whole genomes and of gene deletion mutants, we identified two hitherto uncharacterized chromosomal loci encoding a phospholipase (PlpV) and a collagenase (ColP). PlpV was ubiquitous in the subspecies and exerted hemolytic activity against fish erythrocytes, which was enhanced in the presence of lecithin. ColP was restricted to a fraction of the isolates and was responsible for the collagen-degrading activity in this subspecies. Consistent with the presence of signal peptides in PlpV and ColP sequences, mutants for the type II secretion system (T2SS) genes epsL and pilD exhibited impairments in phospholipase and collagenase activities. Sea bass virulence experiments and cell culture assays demonstrated major contributions of PhlyC and PlpV to virulence and toxicity. IMPORTANCE This study constitutes genetic and genomic analyses of plasmidless strains of an emerging pathogen in marine aquaculture, Photobacterium damselae subsp. damselae. To date, studies on the genetic basis of virulence were restricted to the pPHDD1 plasmid-encoded toxins Dly and PhlyP. However, the vast majority of the recent isolates of this pathogen from fish farm outbreaks lack this plasmid. Here we demonstrate that the plasmidless strains produce two hitherto uncharacterized ubiquitous toxins encoded in chromosome I, namely, the hemolysin PhlyC and the phospholipase PlpV. We report the main roles of these two toxins in fish virulence and in cell toxicity. Our results constitute the basis for a better understanding of the virulence of a widespread marine pathogen.

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Section: Methodsmentioning

confidence: 99%

Chromosome-Encoded Hemolysin, Phospholipase, and Collagenase in Plasmidless Isolates of Photobacterium damselae subsp. damselae Contribute to Virulence for Fish

Vences

Rivas

Lemos

et al. 2017

Appl Environ Microbiol

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“…After 24 h, the medium was replaced with diluted ECPs, purified toxins, or medium controls. ATP in cell lysates was measured luminometrically using a firefly luciferase-based assay as described elsewhere (31).…”

Section: Methodsmentioning

confidence: 99%

Phobalysin, a Small β-Pore-Forming Toxin of Photobacterium damselae subsp. damselae

et al. 2015

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c Photobacterium damselae subsp. damselae, an important pathogen of marine animals, may also cause septicemia or hyperaggressive necrotizing fasciitis in humans. We previously showed that hemolysin genes are critical for virulence of this organism in mice and fish. In the present study, we characterized the hlyA gene product, a putative small ␤-pore-forming toxin, and termed it phobalysin P (PhlyP), for "photobacterial lysin encoded on a plasmid." PhlyP formed stable oligomers and small membrane pores, causing efflux of K ؉ , with no significant leakage of lactate dehydrogenase but entry of vital dyes. The latter feature distinguished PhlyP from the related Vibrio cholerae cytolysin. Attack by PhlyP provoked a loss of cellular ATP, attenuated translation, and caused profound morphological changes in epithelial cells. In coculture experiments with epithelial cells, Photobacterium damselae subsp. damselae led to rapid hemolysin-dependent membrane permeabilization. Unexpectedly, hemolysins also promoted the association of P. damselae subsp. damselae with epithelial cells. The collective observations of this study suggest that membrane-damaging toxins commonly enhance bacterial adherence.

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“…It remains to be seen what secreted staphylococcal toxins, aside from α-toxin, 55 influence the epithelial response. The role of these toxins is important as they can affect the severity of ocular infection including keratitis 56,57 and endophthalmitis.…”

mentioning

confidence: 99%

Response of corneal epithelial cells toStaphylococcus aureus

Heimer

Yamada²,

Russell³

et al. 2010

Virulence

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Pore-forming Staphylococcus aureus ?-toxin triggers epidermal growth factor receptor-dependent proliferation

Cited by 55 publications

References 41 publications

Chromosome-Encoded Hemolysin, Phospholipase, and Collagenase in Plasmidless Isolates of Photobacterium damselae subsp. damselae Contribute to Virulence for Fish

Chromosome-Encoded Hemolysin, Phospholipase, and Collagenase in Plasmidless Isolates of Photobacterium damselae subsp. damselae Contribute to Virulence for Fish

Phobalysin, a Small β-Pore-Forming Toxin of Photobacterium damselae subsp. damselae

Response of corneal epithelial cells toStaphylococcus aureus

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