Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus

Foster, Timothy J.; Geoghegan, Joan A.; Ganesh, Vannakambadi K.; Höök, Magnus

doi:10.1038/nrmicro3161

Cited by 1,164 publications

(1,221 citation statements)

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“…A variety of cell-surface components are involved in intercellular interactions (2,3). Although the polycationic polysaccharide intercellular adhesin has long been thought to be the main component promoting intercellular adhesion (4,5), there is now a compelling body of evidence that cell wall-anchored (CWA) proteins are also involved (2,3). Several recombinant CWA proteins have been shown to form dimers in solution (6)(7)(8)(9).…”

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confidence: 99%

“…A remarkable trait of this bacterium is its ability to form biofilms on implanted devices, thereby triggering infections that are difficult to treat with antibiotics (1,2). Biofilm formation is initiated by attachment of the bacteria to abiotic surfaces, protein-coated materials, and host cells, and followed by cell-cell adhesion and multiplication leading to a mature biofilm (1,2). A variety of cell-surface components are involved in intercellular interactions (2,3).…”

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“…Biofilm formation is initiated by attachment of the bacteria to abiotic surfaces, protein-coated materials, and host cells, and followed by cell-cell adhesion and multiplication leading to a mature biofilm (1,2). A variety of cell-surface components are involved in intercellular interactions (2,3). Although the polycationic polysaccharide intercellular adhesin has long been thought to be the main component promoting intercellular adhesion (4,5), there is now a compelling body of evidence that cell wall-anchored (CWA) proteins are also involved (2,3).…”

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Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC

Feuillie

Formosa-Dague

Hays

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Staphylococcus aureus forms biofilms on indwelling medical devices using a variety of cell-surface proteins. There is growing evidence that specific homophilic interactions between these proteins represent an important mechanism of cell accumulation during biofilm formation, but the underlying molecular mechanisms are still not well-understood. Here we report the direct measurement of homophilic binding forces by the serine-aspartate repeat protein SdrC and their inhibition by a peptide. Using single-cell and single-molecule force measurements, we find that SdrC is engaged in low-affinity homophilic bonds that promote cell-cell adhesion. Low-affinity intercellular adhesion may play a role in favoring biofilm dynamics. We show that SdrC also mediates strong cellular interactions with hydrophobic surfaces, which are likely to be involved in the initial attachment to biomaterials, the first stage of biofilm formation. Furthermore, we demonstrate that a peptide derived from β-neurexin is a powerful competitive inhibitor capable of efficiently blocking surface attachment, homophilic adhesion, and biofilm accumulation. Molecular modeling suggests that this blocking activity may originate from binding of the peptide to a sequence of SdrC involved in homophilic interactions. Our study opens up avenues for understanding the role of homophilic interactions in staphylococcal adhesion, and for the design of new molecules to prevent biofilm formation during infection.Staphylococcus aureus | SdrC | adhesion | biofilms | inhibition T he nosocomial pathogen Staphylococcus aureus is a major cause of superficial and invasive infections. A remarkable trait of this bacterium is its ability to form biofilms on implanted devices, thereby triggering infections that are difficult to treat with antibiotics (1, 2). Biofilm formation is initiated by attachment of the bacteria to abiotic surfaces, protein-coated materials, and host cells, and followed by cell-cell adhesion and multiplication leading to a mature biofilm (1, 2). A variety of cell-surface components are involved in intercellular interactions (2, 3). Although the polycationic polysaccharide intercellular adhesin has long been thought to be the main component promoting intercellular adhesion (4, 5), there is now a compelling body of evidence that cell wall-anchored (CWA) proteins are also involved (2, 3). Several recombinant CWA proteins have been shown to form dimers in solution (6-9). In some cases (i.e., Aap), crystallographic studies have provided insights into the mechanism of dimer formation (9, 10). Although very useful, in vitro methods provide information on purified molecules that are removed from their cellular context. Clearly, elucidating the molecular mechanisms by which CWA proteins self-associate in vivo is key to enhancing our understanding of biofilm accumulation.The increase of multidrug-resistant strains has created an urgent need for new therapeutics for bacterial infections. Biofilm inhibitors, where bacteria are prevented from forming biofilms rather than...

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Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC

Feuillie

Formosa-Dague

Hays

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…It is known that S. aureus can secrete a wide range of proteins, including adhesins (4), nucleases (5,6), complement control proteins (7)(8)(9), and multiple toxins, which interfere with host immune function. Toxins elicit cytotoxicity toward a variety of cells ranging from epithelial cells to leukocytes (1,4,10), and their secretion is associated with lethality in some disease models (11)(12)(13)(14).…”

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confidence: 99%

Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

Das

Lindemann

Young

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection.

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“…Staphylococcus aureus have many different virulence factors, including Cell Wall-Anchored (CWA) proteins that have a vital role in pathogenesis and survival of S. aureus in the environment. Some of the CWA proteins are MSCRAMMs, which have a crucial role in colonization and binding to host extracellular matrix (ECM) (2,3). Many previous studies have suggested that CWA proteins such as ClfB, FnBPs, SasC, protein A, and sasG participate in biofilm formation, which is one of the bacterial approaches for pathogenesis and resistance against antibiotics (4)(5)(6)(7).…”

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confidence: 99%

Genotype Diversity and Evaluation of Biofilm Formation in sasX Positive Methicillin-Resistant Staphylococcus aureus

Eshaghi¹,

Hasannejad‐Bibalan²,

Rohani³

et al. 2017

Avicenna J Clin Microbiol Infect

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Objectives: Staphylococcus aureus surface protein X (sasX) is a newly described protein that has different roles in virulence, such as biofilm formatin, as a bacterial approach for pathogenesis. SasX gene was initially found in eastern Asian countries, yet, studiese have shown spreading of this gene to other strains. Because there is no report on this gene in Iran, the current study aimed at determining the prevalence, genotype diversity, and evaluation of biofilm formation in sasX positive methicillin-resistant Staphylococcus aureus (MRSA). Methods: This experimental study was conducted on strains isolated from inpatients during 2014 to 2015. Cultivation, identification, and confirmation of MRSA isolates were performed. The evaluation of biofilm production, sasX gene detection, and Random amplified polymorphic DNA (RAPD)-polymerase chain reaction (PCR) were done. Data collection and comparison were performed by SPSS and gelcompare softwares. Conclusions: Frequency of sasX gene was somewhat similar to another study in eastern countries and the ability of biofilm formation in sasX + strains compared to all of MRSA isolates were not significant (P value > 0.05) and a correlation was not found between RAPD type and biofilm grade.

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Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus

Cited by 1,164 publications

References 145 publications

Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC

Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC

Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

Genotype Diversity and Evaluation of Biofilm Formation in sasX Positive Methicillin-Resistant Staphylococcus aureus

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