Invasion of human keratinocytes by Staphylococcus aureus and intracellular bacterial persistence represent haemolysin-independent virulence mechanisms that are followed by features of necrotic and apoptotic keratinocyte cell death

Mempel, Martin; Schnopp, Christina; Hojka, M.; Fesq, Heike; Weidinger, Stephan; Schaller, Martin; Körting, Hans Christian; Ring, Johannes; Abeck, Dietrich

doi:10.1046/j.1365-2133.2002.04752.x

Cited by 115 publications

(92 citation statements)

References 41 publications

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“…Moreover, Fn can also serve as a mediator to induce endocytosis and initiate the entry of bacteria when it binds to bacterial Fn-binding proteins (65,66). Thus, the Caco-2 cell binding activity of Fbp68 and the reduced binding effects of C. difficile in Fbp68 or Fn siRNA treated Caco-2 cells suggest an adhesive role for Fbp68.…”

Section: Discussionmentioning

confidence: 95%

Manganese Binds to Clostridium difficile Fbp68 and Is Essential for Fibronectin Binding

Lin¹,

Kuo²,

Koleci³

et al. 2011

Journal of Biological Chemistry

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Clostridium difficile is an etiological agent of pseudomembranous colitis and antibiotic-associated diarrhea. Adhesion is the crucial first step in bacterial infection. Thus, in addition to toxins, the importance of colonization factors in C. difficileassociated disease is recognized. In this study, we identified Clostridium difficile is a Gram-positive, spore-forming anaerobic bacterium that infects people and multiple animal species. Colonization of the gastrointestinal tract may be asymptomatic or cause a variety of disorders, including mild diarrhea, pseudomembranous colitis, and antibiotic-associated diarrhea (1). Recent outbreaks in North America and Europe document the seriousness of C. difficile infection (2). C. difficile toxins, including toxin A, toxin B, and a recently identified toxin, binary ADP-ribosyltransferase toxin C. difficile transferase, are thought to be the primary virulence factors that mediate C. difficile-associated disease (3). Because C. difficile colonizes gastrointestinal tissues and enterocyte-like Caco-2 cells (4, 5), colonization factors are also recognized as important virulence factors of C. difficile. A variety of colonization factors has been identified, including the following: capsule (6); proteolytic enzymes (7, 8); S-layer proteins P36 and P47 (9); adhesins such as SLPA, CCAP6, Fbp68, and 12-kDa protein (4, 9 -14); flagellins such as FliC and FliD (15, 16); and GroEL chaperones (17,18).Adhesion is the first step in bacterial infection, and several adhesins known as microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) 2 contribute to this step (19). MSCRAMMs located on bacterial surfaces mediate adhesion by binding to various extracellular matrices including fibronectin (Fn), laminin, collagen, elastin, and proteoglycan on host surfaces (19). Loss of some of these genes may attenuate virulence, indicating that MSCRAMMs are pivotal mediators of bacterial disease (20). Although a number of MSCRAMMs have been investigated in other bacterial pathogens, only a few clostridial adhesins, such as Fbp68, have been characterized, and the colonization mechanisms of C. difficile are still poorly understood (11).Manganese-binding proteins are important players in bacterial physiology by participating in cation homeostasis (21), carbon metabolism to promote nutrient acquisition (22), signal transduction (23), resistance to oxidative stress (24), and nutrient-deprived stress (25). In addition, the interaction of some bacterial adhesins and ECM components can be modulated by metal ions such as calcium (26,27). To date, the ability of manganese to mediate bacterial adhesion has not been reported.Previously, Fbp68 on the surface of C. difficile was shown to serve as an adhesin by binding to Fn, fibrinogen, and vitronectin (11). Interestingly, antibody to Fbp68 can be detected in sera from patients with C. difficile-associated disease, indicating that Fbp68 can induce a host immune response during C. difficile infection (28). Structural analysis of Fbp68 indicates t...

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Section: Discussionmentioning

confidence: 95%

Manganese Binds to Clostridium difficile Fbp68 and Is Essential for Fibronectin Binding

Lin¹,

Kuo²,

Koleci³

et al. 2011

Journal of Biological Chemistry

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“…Fn also serves as a mediator to induce endocytosis and initiate the entry of bacteria upon binding to bacterial surface proteins (51,52). We tested whether reducing the expression of Fn on Caco-2 cells would impair the ability of Ag85 or Ag85-expressing MAP K-10 to bind to the Caco-2 cells.…”

Section: Volume 287 • Number 3 • January 13 2012mentioning

confidence: 99%

Novel Mycobacteria Antigen 85 Complex Binding Motif on Fibronectin

Kuo

Bell

Hsieh

et al. 2012

Journal of Biological Chemistry

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“…S. aureus is primarily an extracellular pathogen whose colonization and invasion of human tissues and organs can lead to severe cytotoxic effects. Nevertheless, S. aureus can also be internalized by various cells, including nonphagocytic cells, which seems to induce apoptosis (43,72,120). Although S. aureus has the potential to form biofilms (64), S. epidermidis infections are particularly notorious for the formation of thick multilayered biofilms on indwelling catheters and other implanted devices.…”

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confidence: 99%

Mapping the Pathways to StaphylococcalPathogenesis by Comparative Secretomics

Sibbald

Ziebandt

Engelmann

et al. 2006

Microbiol Mol Biol Rev

235

304

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SUMMARY The gram-positive bacterium Staphylococcus aureus is a frequent component of the human microbial flora that can turn into a dangerous pathogen. As such, this organism is capable of infecting almost every tissue and organ system in the human body. It does so by actively exporting a variety of virulence factors to the cell surface and extracellular milieu. Upon reaching their respective destinations, these virulence factors have pivotal roles in the colonization and subversion of the human host. It is therefore of major importance to obtain a clear understanding of the protein transport pathways that are active in S. aureus. The present review aims to provide a state-of-the-art roadmap of staphylococcal secretomes, which include both protein transport pathways and the extracytoplasmic proteins of these organisms. Specifically, an overview is presented of the exported virulence factors, pathways for protein transport, signals for cellular protein retention or secretion, and the exoproteomes of different S. aureus isolates. The focus is on S. aureus, but comparisons with Staphylococcus epidermidis and other gram-positive bacteria, such as Bacillus subtilis, are included where appropriate. Importantly, the results of genomic and proteomic studies on S. aureus secretomes are integrated through a comparative “secretomics” approach, resulting in the first definition of the core and variant secretomes of this bacterium. While the core secretome seems to be largely employed for general housekeeping functions which are necessary to thrive in particular niches provided by the human host, the variant secretome seems to contain the “gadgets” that S. aureus needs to conquer these well-protected niches.

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Invasion of human keratinocytes by Staphylococcus aureus and intracellular bacterial persistence represent haemolysin-independent virulence mechanisms that are followed by features of necrotic and apoptotic keratinocyte cell death

Abstract: Staphylococcal invasion of human keratinocytes represents a potent staphylococcal virulence factor, which, independently of alpha- and beta-haemolysins, leads to necrotic and apoptotic cell damage.

Cited by 115 publications

References 41 publications

Manganese Binds to Clostridium difficile Fbp68 and Is Essential for Fibronectin Binding

Manganese Binds to Clostridium difficile Fbp68 and Is Essential for Fibronectin Binding

Novel Mycobacteria Antigen 85 Complex Binding Motif on Fibronectin

Mapping the Pathways to StaphylococcalPathogenesis by Comparative Secretomics

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