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The Staphylococcal Biofilm: Adhesins, Regulation, and Host Response

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  • Authors: Alexandra E. Paharik1, Alexander R. Horswill2
  • Editors: Indira T. Kudva3, Tracy L. Nicholson4
    Affiliations: 1: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242; 2: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242; 3: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA; 4: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA
  • Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0022-2015
  • Received 26 June 2015 Accepted 24 July 2015 Published 18 March 2016
  • Alexander R. Horswill, [email protected]
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  • Abstract:

    The staphylococci comprise a diverse genus of Gram-positive, nonmotile commensal organisms that inhabit the skin and mucous membranes of humans and other mammals. In general, staphylococci are benign members of the natural flora, but many species have the capacity to be opportunistic pathogens, mainly infecting individuals who have medical device implants or are otherwise immunocompromised. and are major sources of hospital-acquired infections and are the most common causes of surgical site infections and medical device-associated bloodstream infections. The ability of staphylococci to form biofilms makes them highly resistant to chemotherapeutics and leads to chronic diseases. These biofilm infections include osteomyelitis, endocarditis, medical device infections, and persistence in the cystic fibrosis lung. Here, we provide a comprehensive analysis of our current understanding of staphylococcal biofilm formation, with an emphasis on adhesins and regulation, while also addressing how staphylococcal biofilms interact with the immune system. On the whole, this review will provide a thorough picture of biofilm formation of the staphylococcus genus and how this mode of growth impacts the host.

  • Citation: Paharik A, Horswill A. 2016. The Staphylococcal Biofilm: Adhesins, Regulation, and Host Response. Microbiol Spectrum 4(2):VMBF-0022-2015. doi:10.1128/microbiolspec.VMBF-0022-2015.


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The staphylococci comprise a diverse genus of Gram-positive, nonmotile commensal organisms that inhabit the skin and mucous membranes of humans and other mammals. In general, staphylococci are benign members of the natural flora, but many species have the capacity to be opportunistic pathogens, mainly infecting individuals who have medical device implants or are otherwise immunocompromised. and are major sources of hospital-acquired infections and are the most common causes of surgical site infections and medical device-associated bloodstream infections. The ability of staphylococci to form biofilms makes them highly resistant to chemotherapeutics and leads to chronic diseases. These biofilm infections include osteomyelitis, endocarditis, medical device infections, and persistence in the cystic fibrosis lung. Here, we provide a comprehensive analysis of our current understanding of staphylococcal biofilm formation, with an emphasis on adhesins and regulation, while also addressing how staphylococcal biofilms interact with the immune system. On the whole, this review will provide a thorough picture of biofilm formation of the staphylococcus genus and how this mode of growth impacts the host.

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The biofilm life cycle. Recent studies have identified steps present in early stages of biofilm formation. After attachment, bacteria form a lawn of growth, which undergoes an exodus period that leaves several small foci of cells. The exodus phase is mediated by the SaeRS system via nuclease enzyme activity. The foci of cells then develop into a mature biofilm containing tower structures. Final dispersal is mediated by the system via secreted enzymes and phenol-soluble modulins.

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0022-2015
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Cell wall–anchored adhesins. All the cell wall–anchored adhesins contain an N-terminal signal sequence (SS) and a C-terminal portion that is cleaved by sortase A at the LPXTG sequence. MSCRAMMs contain three IgG-like folds (N1, N2, and N3) followed by specific ligand-binding domains. In the Sdr protein subfamily, a variable number of B repeats is found between the IgG-like folds and the SD repeat region. SdrC is shown, which contains two of these B repeats. Similarly, the Isd proteins contain one, two, or three NEAT motifs. IsdA is shown, which has one. In SpA, there are four or five IgG-binding domains, sometimes referred to as domains E, D, A, C, and B. There follows a region containing a variable number of tandem repeats.

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0022-2015
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Regulatory networks in biofilm formation. The quorum-sensing system induces expression of secreted staphopain proteases by inhibiting translation of Rot (repressor of toxins), a negative regulator of the proteases. These proteases then degrade proteins on the staphylococcal surface and in the biofilm matrix. The SaeRS system induces production of the nuclease enzyme that cleaves eDNA in the matrix. Sigma factor B (SigB) inhibits expression, while SarA has been shown to directly enhance it.

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0022-2015
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Macrophage activation pathways. Biofilm growth of has been shown to favor the M2 phenotype in macrophages, which is characterized by increased arginase and profibrotic activity, as well as decreased antimicrobial clearance. These changes are thought to contribute to the persistence of staphylococci in biofilm infections. This figure is reproduced from reference 272 .

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0022-2015
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Categorized cell wall-anchored adhesins

Source: microbiolspec March 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0022-2015

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