Fibronectin-binding proteins (FnBP) in bacteria

Bacterial adhesins represent significant virulence factors in several pathogens (Zhang, 2001) and promote the release of toxins and lead to penetration of host cells (Carbonea et al., 2003). Therefore, the adherence of pathogenic bacteria to host tissues is considered as a critical first step in their pathogenicity (Danny et al., 1999). Adhesion to the intestinal epithelium is an important determinant of virulence for many pathogenic bacteria, allowing them to resist the fluid flow of lumenal contents (Kim et al., 2000).

Most bacterial adhesins recognize and bind to host extracellular matrix (ECM) and other cell surface molecules such as fibronectin (Fn), collagen, fibrinogen/fibrin, elastin, laminin, vitronectin and heparin sulphate-containing proteoglycans (Joh et al., 1999).

These bacterial adhesins which bind to ECM molecules are known as Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs); however, most of these molecules have not been identified and characterised (Danny et al., 1999; Patti et al., 1994; Patti and Hook, 1994). One of the extracellular matrix molecules that binds to MSCRAMMs, is fibronectin (Fn) which has been detailed in Section 1.6.2.1.

Several pathogenic bacteria have the ability to adhere to fibronectin (Fn) including Salmonella enteritidis, Mycobacterium avium, Escherichia coli, Streptococcus pyogenes, Clostridium difficile, Staphylococcus aureus, Neisseria gonorrhoeae, Campylobacter jejuni, and Treponema species (Baloda et al., 1985; Schorey et al., 1996; Visai et al., 1991; Jaffe et al., 1996; Hennequin et al., 2003; Rydén et al., 1983; van Putten et al., 1998; Konkel et al., 1997; Dawson & Ellen, 1994). The first discovery of bacterial FnBP was Staphylococcus aureus (Kuusela et al., 1978) and the next genus shown to bind fibronectin was the Streptococci (Talay et al., 1992). So far, over 100 bacterial FnBP have been identified (Brian et al., 2011), and more than 10 FnBP have been just recognized in streptococci (Schwarz-Linek et al., 2006). Staphylococcus aureus has two recognized genes which were named fnbA and fnbB (Nashev et al., 2004; Peacock et al., 2000; Jansson et al., 1991; Kuusela et al., 1978) and both code for large proteins (>1000 residues). Many other bacteria including Gram-positive (Table 1.5) and Gram-negative (Table 1.6) bacteria have one or more genes encoding FnBPs that bind fibronectin molecules in order to bypass the epithelial barriers and colonize the mammalian hosts.

35 Table 1.5 Gram-positive fibronectin-binding proteins

Bacterium Fibronectin-binding protein Mass (kDa) References

A. pyogenes CbpA 127 Esmay et al., 2003; Pietrocola et al., 2007

Bac. fragilis Omp 102 Brain et al., 2011

Cl. difficile Fbp68(FbpA) 68 Hennequin et al., 2003

Cl. perfringens FbpA, FbpB 25, 66 Katayama et al., 2009

Ent. faecium SagA 53 Zareba et al., 1997; Styriak et al., 2004

Er. rhusiopathiae RpsA, RpsB 219, 85 Shimoji et al., 2003

Lb. brevis SlpA 46 Engelhard, 2007

Lb. plantarum enolase - Esgleas et al., 2008

L. monocytogenes FbpA, Five undefined proteins 55,- Gilot et al., 1999,2000; Dramsi et al., 2004 Mycobacteria spp. Antgen85ABCD, MPT51,Apa/FAP, Wag22

antigen, Malate synthase

31, 30, 31, 28, 30, 71, 80

Wiker and Harboe, 1992; Ohara et al., 1995; Schorey et al., 1995, 1996;; Belisle et al., 1997; Rosseels et al., 2006; Peake et al., 1993; naito et al., 2000; Ronning et al., 2000; Anderson et al., 2001; Kinhikar et al., 2006

Mycoplasma spp. EfTu, PDH-β, HIp3, PlpA 30, 45, 200,

160

Razin et al., 1998; Dallo et al., 2002; May et al., 2006;

Balasubramanian et al., 2008

P. acnes undefined protein 80 Yu et al., 1997

S. aureus FnBPAB, Eap, Emp, Ebh, Aaa/Sle1 106, 104, 15,

36, 1100, 36,

Kuusela et al.,1979; Espersen and Clemmensen, 19982; Flock et al., 1987; Jonsson et al., 1991; Peacock et al., 2000; Nashev et al., 2004

36 Table 1.5 (Continued) Gram-positive fibronectin-binding proteins

Bacterium Fibronectin-binding protein Mass (kDa) References

S. caprae AtlC 154 Allignet et al., 2001

S. epidermidis Aaa/Aae, Embp/Ebh 35, 1000 Heilmann et al., 2003; Christner et al., 2010

S. saprophyticus Aas(AtlC), UaFA 159, 230 Aas Hell et al., 1998; Gatermann and Meyer, 1994; Hell

et al., 1998

Strep. agalactiae ScpB 22 Brown et al., 2005

Strep. dysgalactiae FnBA, FnBB 120, 125 Baums et al., 2006; Lindgren et al., 1992,1993

Strep. equi ssp. equi FnE, FnEB, SFS -, 53, 40 Lindmark et al., 2001; Lannergard et al., 2005; Lindmark and Guss, 1999

Strep. equi ssp.

zooepidemicus

FNZ, FNZ2 65, 54 Natanson et al., 1995; Lindmark et al., 1996; Hong, 2005

Strep. gordonii CshA, CshB, FbpA 265, 244, 63 McNab et al., 1994; McNab and Jenkinson, 1992

Strep. intermedius Antigen I/II 143

Strep. mutans Antigen I/II, FbpA/SmFnB, FBP-130 166, 63, 130 Miller-Torbert et al., 2008

Strep. pneumonia PavA(FbpA), SP-0082, PbfA 63, 91, 74 Lau et al., 2001; Bumbaca et al., 2004; Yamaguchi et al., 2008

Strep. pyogenes PrtF1/SfB1, PrtF2, FbaA, FbaB/PrtF2-Like, Serum opacity factor, Sfbx , Fbp54 (FbpA), GAPDH, Protein H, M1 protein, Shr, 28-kDa protein

69,128,38,81,112,72, 54,36,37,55,143,28

Switalski et al., 1982; Talay et al., 1991,1992; Hanski et al., 1992; Hanski and Caparon, 1992; Katerov et al., 1998; Sela et al., 1993; Ozeri et al., 1996; Talay et al., 2000; Dinkla et al., 2003; Schwarz-Linek et al., 2006 Strep. suis FbpS(FbpA), OFS, Enolase 64, 117, 48 Staats et al., 1997; De Greef et al., 2002; Sun et al., 2005

37 Table 1.6 Gram-negative fibronectin-binding proteins

Bacterium Fibronectin-binding protein Mass (kDa) Reference

A. butzleri Putative CadF, Cj27 37, 47 William et al., 2007

B. henselae BadA, Pap31 328, 29 Batterman et al., 1995; Dabo et al., 2006

B. burgdorferi BBK32, RevA/B 42, 17 Szczepanski et al., 1990; Coburn et al., 2005; Fischer

et al., 2006

C. jejuni CadF,Cj1279c 34, 46 Konkel et al., 1997,1999a

E. coli Curli, P-fimbriae, Pili(HCP), H6/H7 pili, Tsh, Upag -, -, -, -, 142, 178 Froman et al., 1884; Olsen et al., 1989; Visai et al., 1991; Westerlund et al., 1991; Sokurenko et al., 1992,1994; Otto et al., 2005; Valle et al., 2008

H. ducreyi DrsA 26 Bauer and Spinola, 1999; Cole et al., 2002; Leduc et

al., 2008,2009

H. influenzae Pili, Hap -, 154 Virkola et al., 2000; St Geme, 2002

Hel. pylori VacA toxin 136 Papini et al., 2001

L. interrogans LigA, LigB, LenB/C/E, LipL32 78, 201, 25, 32 Faine et al., 1999; Merien et al., 2000; Palaniappan et al., 2002; Matsunaga et al., 2003; Stevenson et al., 2007; Tung et al., 2010

N. gonorrhoeae OpaA 27 Van Putten et al., 1998

Pasteurellaceae spp. ComE1 12 Redfield et al., 2005; Mullen et al., 2006,2007

38 Table 1.6 (Continued) Gram-negative fibronectin-binding proteins

Bacterium Fibronectin-binding protein Mass (kDa) Reference

P. multocida Omp87,Omp16 87, 16 Dabo et al., 2005;

Por. gingivalis Fimbrillin/FimA 37 Sojar et al., 1995; Wu and Fives-Taylor, 2001

Prev. intermedia AdpB 29 Yu et al., 2006; Hirayama et al., 2009

Pesud. aeruginosa OprD, OprE1, OprE2, OprF 37-44 Roger et al., 1999; Rebiere-Huet et al., 1999, 2002, 2004

Sal. typhimurium ShdA, MisL 207, 101 Kingsley et al., 2000,2002; Boyen et al., 2006

Tann. forsythia BspA 114 Sharma et al., 1998

Trep. denticola OppA, Msp 67, 58 Umemoto et al., 1993; Fenno et al., 1998, 2000; Edwards et al.,

2005

Trep. pallidum Several unidentified 32-90 Peterson et al., 19983, 1987; Thomas et al., 1985ab; Cameron et al., 2004; Brinkman et al., 2008

V. vunificus OmpU 35 Sperandio et al., 1995; Goo et al., 2006

Y. pseudouberculosis YadA 41 Tertti et al., 1992

39