Staphylococcus aureus is the leading cause of infection in orthopedic implants and of osteomyelitis consequent to it. Here we focus on the wide array of virulence factors that endow S. aureus with its abilities to colonize peri-prosthesis tissues and to attack and damage them. Following an infective strategy orchestrated by agr locus, Staphylococcus aureus first deploys virulence factors for adhesion to the prosthesis and peri-prosthesis tissues and then launches its attack by delivering destructive factors.
AlexanderE.H., and HudsonM.C.Factors influencing the internalization of Staphylococcus aureus and impacts on the course of infections in humans.Appl Microbiol Biotechnol.2001; 56: 361–366.
3.
JevonsM.P.“Celbenin”-resistant staphylococci.Br Med J.1961; 1: 124–125.
CampocciaD., MontanaroL., ArciolaC.R.The significance of infection related to orthopaedic devices and issues of antibiotic resistance.Biomaterials2006; 27(11): 2331–2339.
6.
CampocciaD., MontanaroL., ArciolaC.R.Current methods for molecular epidemiology studies of implant infections.Int J Artif Organs.2009; 32(9): 642–654.
ArciolaC.R., AnY.H., CampocciaD., DonatiM.E., MontanaroL.Etiology of implant orthopaedic infections: a survey on 1027 clinical isolates.Int J Artif Organs2005; 28(11): 1091–1100.
9.
CampocciaD., MontanaroL., VisaiL.. Characterization of 26 Staphylococcus warneri isolates from orthopedic infections.Int J Artif Organs2010; 33(9): 575–581.
10.
von EiffC., ArciolaC.R., MontanaroL., BeckerK., CampocciaD.Emerging Staphylococcus species as a new pathogens in implant infections.Int J Artif Organs2006; 29: 360–367.
11.
FengY., ChenC.J., SuL.H., HuS., YuJ., ChiuC.H.Evolution and pathogenesis of Staphylococcus aureus: lessons learned from genotyping and comparative genomics.FEMS Microbiol Rev.2008; 32(1): 23–37.
12.
BlancD.S., PetignatC., WengerA.. Changing molecular epidemiology of methicillin-resistant Staphylococcus aureus in a small geographic area over an eight-year period.J Clin Microbiol.2007; 45(11): 3729–3736.
PattiJ.M., AllenB.L., McGavinM.J., HöökM.MSCRAMM-mediated adherence of microorganism to host tissues.Annu Rev Microbiol.1994a; 48: 585–617.
15.
SpezialeP., PietrocolaG., RindiS.. Structural and functional role of Staphylococcus aureus surface components recognizing adhesive matrix molecules of the host.Future Microbiol.2009; 4: 1337–1352.
NavarreW., SchneewindO.Surface proteins of Gram-positive bacteria and mechanisms of their targeting to the cell wall envelope.Microbiol Mol Biol Rev.1999; 63(1): 174–229.
18.
GreeneC., McDevittD., FrancoisP., VaudauxP.E., LewD.P., FosterT.J.Adhesion properties of mutants of Staphylococcus aureus defective in fibronectin-binding proteins and studies on the expression of fnb genes.Mol Microbiol.1995; 17(6): 1143–1152.
19.
HauckC.R., OhlsenK.Sticky connections: extracellular matrix protein recognition and integrin-mediated cellular invasion by Staphylococcus aureus.Curr Opin Microbiol.2006; 9(1): 5–11.
20.
Schwarz-LinekU., WernerJ.M., PickfordA.R.. Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper.Nature.2003; 423(6936): 177–181.
21.
Schwarz-LinekU., HookM., PottsJ.R.The molecular basis of fibronectin-mediated bacterial adherence to host cells.Mol Microbiol.2004; 52: 631–641.
22.
SinhaB., FrancoisP.P., NüsseO.. Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1.Cell Microbiol.1999; 1(2): 101–117.
23.
SinhaB., FrancoisP., QueY.A.. Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells.Infect Immun.2000; 68: 6871–6878.
24.
FowlerT., wannE.R., JohD., JohanssonS., FosterT.J., HookM.Cellular invasion by Staphylococcus aureus involves a fibronectin bridge between the bacterial fibronectin-binding MSCRAMMs and host cell beta1 integrins.Eur J Cell Biol.2000; 79: 672–679.
25.
AgererF., MichelA., OhlsenK., HauckC.R.Integrin-mediated invasion of Staphylococcus aureus into human cells requires Src family protein tyrosine kinases.J Biol Chem.2003; 278: 42524–42531.
26.
EdwardsA.M., PottsJ.R., JosefssonE., MasseyR.C.Staphylococcus aureus host cell invasion and virulence in sepsis is facilitated by the multiple repeats within FnBPA.PLOS Pathog2010; 6(6): e1000964.
27.
EdwardsA.M., MasseyR.C.Invasion of human cells by a bacterial pathogen.J Vis Exp.2011; (49). pii: 2693. DOI: 10.3791/2693.
28.
EdwardsA.M., PotterU., MeenanN.A., PottsJ.R., MasseyR.C.Staphylococcus aureus keratinocyte invasion is dependent upon multiple high-affinity fibronectin-binding repeats within FnBPA.PLoS One.2011; 6(4): e18899.
29.
ShinjiH., YosizawaY., TajimaA.. Role of fibronectin-binding proteins A and B in in vitro cellular infections and in vivo septic infections by Staphylococcus aureus.Infect Immun.2011; 79(6): 2215–23.
30.
TestoniF., MontanaroL., CampocciaD., VisaiL., ArciolaC.R.Internalization by osteoblasts of two Staphylococcus aureus clinical isolates differing in their adhesin gene pattern.Int J Artif Organs.2011; 34(9): 789–798.
31.
PeacockS.J., DayN.P., ThomasM.G., BerendtA.R., FosterT.J.Clinical isolates of Staphylococcus aureus exhibit diversity in fnb genes and adhesion to human fibronectin.J Infect.2000; 41: 23–31.
32.
PeacockS.J., MooreC.E., JusticeA.. Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus.Infect Immun.2002; 70(9): 4987–4996.
33.
PattiJ.M., BolesJ.O., HöökM.Identification and biochemical characterization of the ligand binding domain of the collagen adhesin from Staphylococcus aureus.Biochemistry.1993; 32(42): 11428–11435.
34.
SwitalskiL.M., PattiM., ButcherW., GristinaA.G., SpezialeP., HookM.A collagen receptor on Staphylococcus aureus strains isolated from patients with septic arthritis mediates adhesion to cartilage.Mol Microbiol.1993; 7: 99–107.
35.
MontanaroL., ArciolaC.R., BaldassarriL., BorsettiE.Presence and expression of collagen adhesin gene (cna) and slime production in Staphylococcus aureus strains from orthopaedic prosthesis infections.Biomaterials.1999; 20(20): 1945–1949.
36.
PattiJ.M., BremellD., Krajewska-PietrasikA.. The Staphylococcus aureus collagen adhesin is a virulence determinant in experimental septic arthritis.Infect Immun.1994b; 62: 152–161.
37.
ElasriM.O., ThomasJ.R., SkinnerR.A.. Staphylococcus aureus collagen adhesion contributes to the pathogenesis of osteomyelitis.Bone.2002; 30(1): 275–280.
38.
HienzS.A., SchenningsT., HeimdahlA., FlockJ.L.Collagen binding of Staphylococcus aureus is a virulence factor in experimental endocarditis.J Infect Dis.1996; 174: 83–88.
39.
RhemM.N., LechE.M., PattiJ.M.. The collagen-binding adhesion is a virulence factor in Staphylococcus aureus keratitis.Infect Immun.2000; 68: 3776–3779.
40.
HolderbaumD., SpechT., EhrhartL.A., KeysT., HallG.S.Collagen binding in clinical isolates of Staphylococcus aureus.J Clin Microbiol.1987; 25: 2258–2261.
41.
RydingU., FlockJ.I., FlockM., SoderquistB., ChristenssonB.Expression of collagen-binding protein and type 5 and 8 capsular polysaccharide in clinical isolates of Staphylococcus aureus.J Infect Dis.1997; 176: 1096–1099.
42.
ThomasM.G., PeacockS., DaenkeS., BerendtA.R.Adhesion of Staphylococcus aureus to collagen is not a major virulence determinant for septic arthritis, osteomyelitis, or endocarditis.J Infect Dis.1999; 179: 291–293.
43.
CampocciaD., SpezialeP., RavaioliS.. The presence of both bone sialoprotein-binding protein gene and collagen adhesin gene as a typical virulence trait of the major epidemic cluster in isolates from orthopedic implant infections.Biomaterials.2009; 30(34): 6621–8.
44.
NakakidoM., TanakaY., TsumotoK.The N-terminal domain of elastin-binding protein of Staphylococcus aureus changes its secondary structure in a membrane-mimetic environment.J Biochem.2007; 142(2): 131–134.
45.
CampocciaD., MontanaroL., RavaioliS., CanginiI., SpezialeP., ArciolaC.R.Description of a new group of variants of the Staphylococcus aureus elastin-binding protein that lacks an entire DNA segment of 180 bp.Int J Artif Organs.2009; 32(9): 621–629.
46.
SabatA., MellesD.C., MartirosianG., GrundmannH., van BelkumA., HryniewiczW.Distribution of the serine-aspartate repeat protein-encoding sdr genes among nasal-carriage and invasive Staphylococcus aureus strains.J Clin Microbiol.2006; 44(3): 1135–1138.
47.
TungH., GussB., HellmanU., PerssonL., RubinK., RydénC.A bone sialoproteina-binding protein from Staphylococcus aureus: a member of the staphylococcal Sdr family.Biochem J.2000; 345(Pt 3): 611–619.
48.
PerssonL., JohanssonC., RydénC.Antibodies to Staphylococcus aureus bone sialoprotein-binding protein indicate infectious osteomyelitis.Clin Vaccine Immunol.2009; 16(6): 949–952.
49.
JosefssonE., McCreaK.W., Nì EidhinD.. Three new members of the serine-aspartate repeat protein multigene family of Staphylococcus aureus.Microbiology.1998; 144(Pt 12): 3387–3395.
50.
TradS., AllignetJ., FranguelL.. DNA macroarray for identification and typing of Staphylococcus aureus isolates.J Clin Microbiol.2004; 42(5): 2054–2064.
51.
HeilmannC., SchweitzerO., GerkeC.. Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis.Mol Microbiol.1996; 20: 1083–1091.
52.
GerkeC., KraftA., SussmuthR.. Characterization of the N-acetylglucosaminyltransferase activity involved in the biosynthesis of the Staphylococcus epidermidis polysaccharide intercellular adhesin.J Biol Chem.1998; 273: 18586–18593.
53.
CramtonS.E., GerkeC., SchnellN.F.. The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation.Infect Immun.1999; 67: 5427–5433.
54.
ArciolaC.R., BaldassarriI., MontanaroL.Presence of icaA and icaD genes and slime production in a collection of staphylococcal strains from catheter-associated infections.J Clin Microbiol.2001; 39: 2151–2156.
55.
ArciolaC.R., BaldassarriL., MontanaroL.In catheter infections by Staphylococcus epidermidis the intercellular adhesion (ica) locus is a molecular marker of the virulent slime-producing strains.J Biomed Mater Res.2002; 59(3): 557–562.
56.
WhitchurchC.B., Tolker-NielsenT., RagasP.C.. Extracellular DNA required for bacterial biofilm formation.Science.2002; 295: 1487.
57.
Allesen-HolmM., BarkenK.B., YangL.. A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms.Mol Microbiol.2006; 59: 1114–1128.
58.
ThomasV.C., HancockL.E.Suicide and fratricide in bacterial biofilms.Int J Artif Organs.2009; 32(9): 537–544. Review
59.
ArciolaC.R., VisaiL., RavaioliS., CanginiI., CampocciaD., MontanaroL.Extracellular DNA in biofilms.Int J Artif Organs.2011; 34(9): 824–831.
60.
SchierholzJ.M., BeuthJ.Implant infections: a haven for opportunistic bacteria.J Hosp Infect.2001; 49(2): 87–93. Review.
61.
BeechI.B., SunnerJ., ArciolaC.R., CristianiP.Microbially influenced corrosion: damage to prostheses, delight for bacteria.Int J Artif Organs.2006; 29(4): 443–452.
62.
BoneR.C.Gram-positive organisms and sepsis.Arch Int Med.1994; 154: 26–34.
CedergrenL., AnderssonR., JanssonB., UhlenM., NilssonB.Mutational analysis of the interaction between staphylococcal protein A and human IgG1.Protein Eng.1993; 6: 441–448.
65.
HairP.S., wardM.D., SemmesO.J., FosterT.J., CunnionK.M.Staphylococcus aureus clumping factor A binds to complement regulator factor I and increases factor I cleavage of C3b.J Infect Dis.2008; 198(1): 125–133.
66.
O'SeaghdhaM., van SchootenC.J., KerriganS.W.. Staphylococcus aureus protein A binding to von Willebrand factor A1 domain in mediated by conserved IgG binding regions.FEBS J2006; 273: 4831–4841.
67.
GomezM.I., O'SeaghdhaM., MagargeeM., FosterT.J., PrinceA.S.Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains.J Biol Chem.2006; 281: 20190–20196.
68.
ClaroT., WidaaA., O'SeaghdhaM.. Staphylococcus aureus protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis.PloS One.2011; 6(4): e18748.
69.
JongeriusI., KöhlJ., PandeyM.K.. Staphylococcal complement evasion by various convertase-blocking molecules.J Exp Med.2007; 204(10): 2461–2471.
70.
KanekoJ., KamioY.Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes.Biosci Biotechnol Biochem.2004; 68: 981–1003.
71.
MenestrinaG., SerraM.D., PrevostG.Mode of action of Betabarrel pore-forming toxins of the staphylococcal alfa-hemolysin family.Toxicon.2001; 39: 1661–1672.
MontanaroL., BaldassarriL., CorazzariT.. Panton-Valentine leukocidin gene detected in Staphylococcus aureus strain isolated from a knee arthroprosthesis infection.Int J Artif Organs.2009; 32(9): 630–634.
74.
CampocciaD., BaldassarriL., PiriniV., RavaioliS., MontanaroL., ArciolaC.R.Molecular epidemiology of Staphylococcus aureus from implant orthopaedic infections: Ribotypes, agr polymorphism, leucocidal toxins and antibiotic resistance.Biomaterials.2008; 29: 4108–4116.
75.
LarkinE.A., CarmanR.J., KrakauerT., StilesB.G.Staphylococcus aureus: the toxic presence of a pathogen extraordinaire.Curr Med Chem.2009; 16(30): 4003–4019.
76.
Le LoirY., BaronF., GautierM.Staphylococcus aureus and food poisoning.Genet Mol Res.2003; 2: 63–76.
77.
CunninghamR., CockayneA., HumphreysH.Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections.J Med Microbiol.1996; 44: 157–164.
CostertonJ.W., MontanaroL., ArciolaC.R.Bacterial communications in implant infections: a target for an intelligence war.Int J Artif Organs.2007; 30(9): 757–763. Review.
80.
SørensenS.J., BaileyM., HansenL.H.. Studying plasmid horizontal transfer in situ: a critical review, Nat Rev Microbiol.2005; 3: 700–710.
81.
LivermoreD.M.Antibiotic resistance in staphylococci.Int J Antimicrob Agents.2000; 16(S1): 3–10.
82.
ArciolaC.R., CampocciaD., GamberiniS.. Search for the insertion element IS256 within the ica locus of Staphylococcus epidermidis clinical isolates collected from biomaterial-associated infections.Biomaterials.2004; 25: 4117–4125.
83.
MontanaroL., CampocciaD., PiriniV.. Antibiotic multiresistance strictly associated with IS256 and ica genes in Staphylococcus epidermidis strains from implant orthopedic infections, J Biomed Mater Res A.2007; 83: 813–818.
84.
CampocciaD., MontanaroL., PiriniV.. Prevalence of genes for aminoglycoside-modifying enzymes in Staphylococcus epidermidis isolates from orthopedic postsurgical and implant-related infections.J Biomed Mater Res A.2009; 88: 654–663.
MolinS., Tolker-NielsenT.Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure.Curr Opin Biotechnol.2003; 14: 255–261.
87.
FosterT.J.Colonization and infection of the human host by staphylococci: adhesion, survival and immune evasion.Vet Dermatol.2009; 20(5-6): 456–470.
88.
DubinG.Extracellular proteases of Staphylococcus spp.Biol Chem.2001; 383(7-8): 1075–1086.
89.
OttoM.Basis of virulence in community-associated methicillin-resistant Staphylococcus aureus.Annu Rev Microbiol.2010; 64: 143–162.
90.
MontanaroL., CampocciaD., ArciolaC.R.Advancements in molecular epidemiology of implant infections and future perspectives.Biomaterials.2007; 28: 5155–5168.
91.
ArciolaC.R., CampocciaD., BaldassarriL.. Detection of biofilm formation in Staphylococcus epidermidis from implant infections. Comparison of a PCR-method that recognizes the presence of ica genes with two classic phenotypic methods.J Biomed Mater Res A.2006; 76(2): 425–30.
CampocciaD., ArciolaC.R., CervellatiM.. In vitro behaviour of bone marrow-derived mesenchymal cells cultured on fluorohydroxyapatite-coated substrata with different roughness.Biomaterials.2003; 24(4): 587–596.
98.
ArciolaC.R., MontanaroL., GiordanoM.. Hydroxyapatite-coated orthopaedic screws as infection resistant materials: In vitro study.Biomaterials.1999; 20(4): 323–7.