Effect of alpha-toxin and capsular exopolysaccharide on the adherence of Staphylococcus aureus to cultured teat, ductal and secretory mammary epithelial cells

Cifrian, E.; Guidry, A.J.; O’Brien, Celia; Marquardt, W. W.

doi:10.1016/0034-5288(95)90083-7

Cited by 19 publications

(12 citation statements)

References 31 publications

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“…Our findings add important new information by showing (i) that hemolysins increase the association of Gram-positive or Gram-negative bacteria with mammalian cells, (ii) that the effect does not depend on chemotaxis, (iii) that it is independent of pili, and (iv) that it depends on an active response of target cells, which is apparently under the control of class III PI3Ks. Because the virulence of bacteria correlates with levels of adherence to cultured cells (66,67), the results call for further studies along these lines.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Hypothetically, a reduced intestinal barrier function could lead to translocation of intraluminal bacteria and their dissemination to various internal tissues followed by secondary infections and multiple organ dysfunction syndrome (3,12). Some enteropathogenic bacteria cause intestinal barrier dysfunction directly (15,42).…”

Section: Discussionmentioning

confidence: 99%

The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

et al. 2012

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ABSTRACTIncreased microvascular permeability is a hallmark of sepsis and septic shock. Intestinal mucosal dysfunction may allow translocation of bacteria and their products, thereby promoting sepsis and inflammation. AlthoughStaphylococcus aureusalpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects ofS. aureusalpha-toxin on human epithelial barrier functions. We hypothesize thatS. aureusalpha-toxin in the blood can impair the intestinal epithelial barrier and thereby facilitate the translocation of luminal bacteria into the blood, which may in turn aggravate a septic condition. Here, we showed that staphylococcal alpha-toxin disrupts the barrier integrity of human intestinal epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER) and reduced cellular levels of junctional proteins, such as ZO-1, ZO-3, and E-cadherin. The Caco-2 cells also responded to alpha-toxin with an elevated cytosolic calcium ion concentration ([Ca2+]i), elicited primarily by calcium influx from the extracellular environment, as well as with a significant reduction in TER, which was modulated by intracellular calcium chelation. Moreover, a significantly larger reduction in TER and amounts of the junctional proteins,viz., ZO-3 and occludin, was achieved by basolateral than by apical application of the alpha-toxin. These experimental findings thus support the hypothesis that free staphylococcal alpha-toxin in the bloodstream may cause intestinal epithelial barrier dysfunction and further aggravate the septic condition by promoting the release of intestinal bacteria into the underlying tissues and the blood.

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“…Indeed, Kiser et al (19) demonstrated that a mutant defective in CP5 production colonized the nares of mice as well as the parental strain at 1 week, but it showed reduced levels of colonization 2 weeks after inoculation. Furthermore, CP1 and CP2 have been implicated in the masking of cell surface adhesins (11,14,33). Thus, CP5 and CP8 may not have a role in initial colonization, but they may play a role during spreading from the initial site to the secondary sites.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Staphylococcus aureus Capsular Polysaccharide Expression by agr and sarA

Luong

Gómez

et al. 2002

Infect Immun

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This study addresses the regulation of Staphylococcus aureus type 8 capsular polysaccharide (CP8) expression by the global regulators agr and sarA. We analyzed CP8 production, cap8-specific mRNA synthesis, and blaZ reporter gene activities of the transcriptional and translational fusions in strain Becker and its agr, sarA, and agr-sarA isogenic mutants during different phases of bacterial growth. In the wild-type strain, cap8 mRNA was undetectable until the mid-logarithmic phase of growth, whereas CP8 production was undetectable until 2 h later, at the onset of stationary phase. The delay most likely reflects the time needed for completing CP8 synthesis resulting from translation of cap8 mRNA. The agr mutation caused drastic reductions in CP8 production and cap8 gene transcription, suggesting that agr is a major positive regulator of CP8 expression. The results of gene fusion studies indicated that regulation by agr is exerted at the transcriptional level. In contrast, the sarA mutation caused only a slight reduction in cap8 mRNA synthesis and reporter gene activities. By comparing CP8 production and cap8 transcription, we observed that sarA affected CP8 production both trancriptionally and posttranslationally. We showed that agr was a major activator for cap gene expression not only in type 8 strain Becker but also in strains representing the four agr groups.More than 90% of Staphylococcus aureus strains produce capsular polysaccharide (CP). Eleven serotypes of staphylococcal CP have been identified, but only CP type 1 (CP1), CP2, CP5, and CP8 have been chemically characterized. CP1 and CP2 have been shown to be antiphagocytic virulence factors. Strains producing CP1 and CP2 are heavily encapsulated; however, these strains are rarely isolated clinically. In fact, more than 80% of clinical isolates produce either CP5 or CP8 (see reference 23 for a review). Recently, CP5 has been shown to play an important role in the pathogenesis of S. aureus, most probably by allowing the organism to resist uptake and killing by phagocytes (1,27,43). Because of their prevalence, CP5 and CP8 have been used as targets for vaccine development, and specific antibodies against CP5 and CP8 have been shown to be protective against S. aureus infections (13, 24).The cap1, cap5, and cap8 gene clusters, required for the synthesis of CP1, CP5, and CP8, respectively, have been cloned and sequenced. The cap5 and cap8 operons are allelic, whereas the cap1 locus is located at a different location. Twelve of the 16 genes in the cap5 and cap8 operons have high degrees of similarity, which reflects the fact that the repeating units of CP5 and CP8 are almost identical (23). Transcriptional analyses have shown that all 16 genes of the cap8 locus are transcribed as a large transcript from a major promoter upstream of the first gene, cap8A. Although several internal promoters within the cap8 gene cluster have also been identified by genetic complementation and reporter gene fusion studies, these internal promoters are much weaker than the primary pro...

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Effect of alpha-toxin and capsular exopolysaccharide on the adherence of Staphylococcus aureus to cultured teat, ductal and secretory mammary epithelial cells

Cited by 19 publications

References 31 publications

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

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

The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

Regulation of Staphylococcus aureus Capsular Polysaccharide Expression by agr and sarA

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