The Fibronectin-Binding Proteins of
            <i>Staphylococcus aureus</i>
            May Promote Mammary Gland Colonization in a Lactating Mouse Model of Mastitis

Brouillette, Éric; Talbot, Brian G.; Malouin, François

doi:10.1128/iai.71.4.2292-2295.2003

Cited by 58 publications

(37 citation statements)

References 29 publications

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“…S. aureus expresses a series of adhesins which can facilitate the organism's adherence to and/or invasion of nonphagocytic cells by interacting with extracellular matrix components of the host, such as collagen, fibrinogen, and fibronectin (17). Although there are some contradictory results from different models of infection (7,8,16,35,40,44,48), fibronectin-binding proteins are the main surface-associated proteins that function as adhesins and invasins by assembling the extracellular matrix protein Fn, which bridges to host cell receptors, such as ␣ 5 ␤ 1 -integrin (13,19,54). It has been demonstrated that fibronectinbinding proteins play a critical role in S. aureus infective endocarditis (35,50,60) and osteomyelitis (32,42).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

et al. 2006

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Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding ␣-, ␤-, and ␥-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

et al. 2006

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“…In the work of Salasia et al (36), fnbA was more common than fnbB in S. aureus isolates originating from cows with bovine mastitis in Indonesian and German dairy herds. The proteins FnBPA and FnBPB enable the attachment of S. aureus to host tissues, facilitate the invasion of the organism into epithelial cells (4,48), and are involved in the colonization of other surfaces like medical devices (11). Strains not expressing FnBPA and FnBPB were demonstrated previously to have highly reduced abilities to invade bovine mammary epithelial cells in vitro (5).…”

Section: Discussionmentioning

confidence: 99%

Molecular Types and Genetic Profiles of Staphylococcus aureus Strains Isolated from Bovine Intramammary Infections and Extramammary Sites

et al. 2008

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Staphylococcus aureus isolates collected from sites of intramammary infection during a 10-month period and from extramammary sites (dairy cow teat skin, teat canals, and skin lesions; milking liners; and hands and nostrils of milking personnel) at two separately managed Finnish dairy herd establishments were analyzed to study the sources and reservoirs of bovine S. aureus intramammary infection. Selected isolates were subjected to pulsed-field gel electrophoresis (PFGE) typing and PCR analysis for genes encoding hemolysins (hla to hlg), leukocidins (lukED and lukM), superantigens (sea, sec, sed, seg to seo, seu, and tst), adhesins (fnbA and fnbB), and penicillin and methicillin resistance (blaZ and mecA). S. aureus was found throughout the herds in 94% of the cows. Nine PFGE types were found, with the herds each having their own predominant type and sharing one type. The degree of diversity of PFGE types in herd II, which integrated foreign heifers, was higher than that in herd I. For both herds, the majority of the PFGE-typed isolates both from milk and from extramammary sites represented the predominant PFGE types. In isolates from herd I, the most prevalent genes were hla-hlg, lukED, and fnbA; in those from herd II, they were hla, hld, hlg, lukED, and fnbA. The other genes were pulsotype linked within the herds. The predominant PFGE types carried both fnbA and fnbB; only fnbA was detected in the other PFGE types. No connection between specific virulence genes and the origins of isolates was found. The results suggest that for the two herds, most S. aureus isolates from extramammary sites were indistinguishable from the isolates infecting the mammary gland and that those sites can thus act as origins and reservoirs of intramammary infections. However, contamination in the opposite direction cannot be excluded.

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“…However, so far, often conflicting results have been reported that argue for (3,22,29,38,49) or against (2,5,10,33,41) their role as virulence factors in a given model in vivo. In most situations, the adhesive and invasive functions of FnBPs are the likely functional link in pathogenicity.…”

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confidence: 99%

Truncation of Fibronectin-Binding Proteins in Staphylococcus aureus Strain Newman Leads to Deficient Adherence and Host Cell Invasion Due to Loss of the Cell Wall Anchor Function

et al. 2004

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Staphylococcus aureus fibronectin-binding proteins (FnBPs) play a critical role in S. aureus pathogenesis. FnBPs mediate adhesion to fibronectin and invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, by fibronectin bridging to the host cell fibronectin receptor integrin (␣ 5 )␤ 1 . Strain Newman is a laboratory strain frequently used for genetic, functional, and in vivo studies. However, despite pronounced production of FnBPs, strain Newman is only weakly adherent to immobilized Fn and weakly invasive. We examined whether these effects are due to a structural difference of FnBPs. Here, we show that both fnbA Newman and fnbB Newman contain a centrally located point mutation resulting in a stop codon. This leads to a truncation of both FnBPs at the end of the C domain at identical positions. Most likely, the stop codon occurred first in fnbB Newman and was subsequently transferred to fnbA Newman by replacement of the entire region encompassing the C, D, and W domains with the respective sequence of fnbB Newman . Using heterologous expression in Staphylococcus carnosus, we found that truncated FnBPs were completely secreted into the culture medium and not anchored to the cell wall, since they lack the sortase motif (LPETG). Consequently, this led to a loss of FnBP-dependent functions, such as strong adhesion to immobilized fibronectin, binding of fibrinogen, and host cell invasion. This mutation may explain some of the earlier reported conflicting data with strain Newman. Thus, care should be taken when drawing negative conclusions about the role of FnBPs as a virulence factor in a given model. Staphylococcus aureus fibronectin-binding proteins (FnBPs)appear to play a critical role in S. aureus pathogenesis (35), as has been shown, e.g., for infective endocarditis (29, 49) and osteomyelitis (22). However, so far, often conflicting results have been reported that argue for (3,22,29,38,49) or against (2, 5, 10, 33, 41) their role as virulence factors in a given model in vivo. In most situations, the adhesive and invasive functions of FnBPs are the likely functional link in pathogenicity. Adhesion to fibronectin and invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, depend on fibronectin bridging between FnBPs and the host fibronectin receptor integrin (␣ 5 )␤ 1 (54).During the analysis of the mechanism for cellular invasion of S. aureus, we found that several reference strains are invasion deficient compared to clinical isolates (54). Strain Newman is a laboratory strain frequently used for genetic, functional, and in vivo studies. Despite strong production of FnBPs (57), strain Newman is only weakly adherent to immobilized Fn and weakly invasive (54). Another often-used reference strain, 8325-4, is also only weakly invasive (54); however, this appears to be due to regulatory defects resulting in low FnBP expression rather than structural FnBP modifications. Strain 8325-4 has a regulatory defect (rsbU) (28) and expresses FnBPs at a low level (6...

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The Fibronectin-Binding Proteins of Staphylococcus aureus May Promote Mammary Gland Colonization in a Lactating Mouse Model of Mastitis

Cited by 58 publications

References 29 publications

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

Molecular Types and Genetic Profiles of Staphylococcus aureus Strains Isolated from Bovine Intramammary Infections and Extramammary Sites

Truncation of Fibronectin-Binding Proteins in Staphylococcus aureus Strain Newman Leads to Deficient Adherence and Host Cell Invasion Due to Loss of the Cell Wall Anchor Function

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