Bacterial Adhesion and Entry into Host Cells

“…of the EPEC/ EHEC TTSS is Tir ( t ranslocated i ntimin r eceptor), which is injected into host target cells and then is inserted into the host-cell membrane, where it functions as a receptor for another LEE encoded molecule, the outer membrane protein intimin (Kenny et al., 1997)(Figure 3A).”

“BabA recognizes the Lewis b (Le b ) blood group antigen present on red blood cells and in the gastric mucosa (Ilver et al., 1998); inflammation of the gastric tissue leads to increased expression of other Lewis antigens normally expressed at low levels such as sialylated sLe x and sLe a , and H.…”

“Cdc42 and RhoA are also required for the FimH-dependent cell invasion process by UPEC (Martinez and Hultgren, 2002).”

“Both pathogens trigger important cytoskeletal changes at the host-cell plasma membrane to promote invasion (Cossart and Sansonetti, 2004).”

“…of other Lewis antigens normally expressed at low levels such as sialylated sLe x and sLe a , and H. pylori recognizes these molecules via the sialic acid binding protein (SabA) (Mahdavi et al., 2002), suggesting that H. pylori infection favors the expression of its own receptors in target tissues.”

“…leader peptide for secretion across the inner membrane, a C-terminal domain that forms a pore in the outer membrane, and a passenger domain that is autotransported through the outer membrane pore to be exposed on the bacterial surface, for cleavage in certain cases (Henderson et al., 2004).”

“…effectors, SopE and SopE2, are bona fide guanine nucleotide exchange factors (GEFs) for Cdc42 and Rac1 and mimic host-cell GEFs, catalyzing the GTP loading and activation of these small GTPases, which results in formation of membrane extensions required for bacterial engulfment (Hardt et al., 1998).”

“Invasin is related to EPEC/EHEC intimins and binds with high affinity to multiple members of the b 1 chain integrin family (Isberg and Leong, 1990), subvert-ing normal interactions of these adhesion molecules with fibronectin.”

“…of polymeric adhesive surface structures expressed by many Gram-negative bacteria including pathogens such as EPEC, EHEC, Salmonella enterica serovar Typhi, Pseudomonas aeruginosa, Legionella pneumophila, Neisseria gonorrhoeae , Neisseria meningitidis, and Vibrio cholerae (Craig et al., 2004).”

“Traversal of the intestinal barrier and of the feto-placental barrier by subversion of cellular E-cadherin function by InlA has been established (Lecuit et al., 2001, 2004), and it is suspected that traversal of the blood-brain barrier probably also requires InlA/E-cadherin interactions.”

“The first bacterial invasion protein ever described was invasin (Isberg et al., 1987), a surface protein of Y. enterocolitica and Y. pseudo-tuberculosis .”

“In fact, S. enterica translocates another SPI-1-TTSS effector, SptP, which is a GAP for both Cdc42 and Rac1, accelerating the GTP hydrolysis and the consequent inactivation of these Rho GTPases after invasion (Fu and Galan, 1999).”

“The main cellular receptor for InlB is the hepatocyte growth factor receptor Met, a receptor tyrosine kinase (Shen et al., 2000), which binds to the leucine rich repeats of InlB.”

“Potentiation of L. monocytogenes entry into target cells by InlA and InlB also requires other cell surface proteins such as the autolysins Ami and Auto, or the choles-terol-dependent cytolysin listeriolysin O (LLO) (Dussurget et al., 2004).”

“The main characterized receptor for the adhesin FimH in bladder epithelial cells is the monomannose moiety of the tetraspanin molecule ur-oplakin 1a (UP1a) (Zhou et al., 2001b).”

“…pili have been unwittingly used during more than five decades for serotyping; new data show that immunization of mice with recombinant S. pyogenes pilus proteins confers protection against challenge with virulent bacteria, highlighting the key role of these pili for infection (Mora et al., 2005).”

“In the case of Neisseria spp., PilC-mediated adhesion to host cells via recognition of the complement regulator CD46 has been reported (Kallstrom et al., 1997), but recent studies suggest that the PilC ligand is a still undefined protein (Kirchner and Meyer, 2005).”

“…of polymorphic cutaneo-mucosal infections and toxic shock syndromes, also express fibro-nectin binding proteins that present mechanico-functional properties similar to those of the streptococcal proteins, despite absence of phylogenetical relationships between them (Schwarz-Linek et al., 2003).”

“…reported to bind some other glycosylated and nonglycosylated receptors different from UP1a, including extracellular matrix structural proteins (laminin and fibronectin), CEACAMs, and the GPI-anchored protein CD48, which mediates FimH-dependent entry of UPEC in mast cells (Shin et al., 2000).”

“Integrity of lipids rafts is also required for the InlB-dependent pathway; however, in contrast to the InlA/E-cadherin case, it is not the initial interaction be-tween InlB and Met that is favored by lipid rafts, but the signaling downstream of PI3K activation (Seveau et al., 2004).”

“As shown recently, Cbl promotes the recruitment and activity of the clathrin-dependent endocytosis machinery at the site of bacterial entry and bacterial internalization (Veiga and Cossart, 2005) (Figure 5B).”

“EHEC Tir generates pedestals in the absence of phosphotyrosines or Nck by associating with the TTSS effector EspF U , which binds N-WASP and stimultates Nck-independent actin assembly (Campellone et al., 2004; Garmendia et al., 2004).”

“…SopB, decreasing the plasma membrane levels of phos-phatidylinositol-4,5-biphosphate and consequently limiting the membrane/cytoskeleton interactions favored by this phosphoinositide; IpgD thus promotes extension of membrane filopodia necessary for bacterial engulfment (Niebuhr et al., 2002).”

“A similar sortase-mediated export of pilin sub-units seems to exist in other pathogenic species such as Clostridium perfringens , Actinomyces naeslundii, Streptococcus agalactiae, Streptococcus mutans, and Streptococcus pneumoniae (Lauer et al., 2005).”

“…matrix (Jon-quieres et al., 2001), and soluble InlB can interact through its GW motifs with a host-cell membrane molecule, the r e-ceptor for the g lobular head of complement C1q molecule (gC1q-R) (Braun et al., 2000); however, the functional significance of this interaction is not understood yet.”

“The Abl/Arg tyrosine kinases phosphorylate the molecular adaptor Crk, which presumably activates a GEF for Cdc42 and Rac1 (Burton et al., 2003).”

“The half-life of SptP is longer than that of SopE or SopE2, assuring in the long term the balance toward recovery of the normal cell architecture after bacterial internalization (Kubori and Galan, 2003).”

“…binds to integrins with higher affinity than fibronectin, and crystal structure of invasin reveals that it presents an optimized surface for integrin binding, including several key residues shared with fibro-nectin, but in the context of different folds and surface shapes (Hamburger et al., 1999).”

“For example, the major adhesins SfbI of S. pyogenes and FnBP-A of S. aureus bind ECM-associated fibronectin and induce the clustering of fibronectin bound integrin receptors, triggering intracellular signaling (Ozeri et al., 2001; Joh et al., 1999; see below).”

“…pathogen Listeria monocytogenes is an intracellular parasite able to traverse three human bar-riers—the intestinal barrier, the blood-brain barrier, and the feto-placental barrier—leading to several clinical manifestations including gastroenteritis, meningitis, or abortion (Dussurget et al., 2004).”

“Unlike type I and P pili, which are assembled in the bacterial extracellular space, type IV pili are formed at the cytoplasmic membrane and the intact organelle is extruded across the outer membrane (Wolfgang et al., 2000).”

“PapG variants recognize different but related Gal a -(1-4)-Gal receptors differently distributed within host tissues and within the host population, so differential expression of PapG adhesins drives tissue and host specificity (Hultgren et al., 1991).”

“…buccal pathogen Streptococcus parasanguis , the distal FimA subunit promotes adhesion to saliva-coated hydroxyl apatite; Actinomyces spp., another buccal pathogen, binds salivary proline-rich molecules and mucosal tissues via type 1 and type 2 fim-bria, respectively (Ton-That and Schneewind, 2004).”

“Another family of adherent structures secreted by the chaperone/usher pathway is the extremely heterogeneous family of Afa/Dr adhesins (Servin, 2005), identified in UPEC and DAEC.”

“Traversal of the intestinal barrier and of the feto-placental barrier by subversion of cellular E-cadherin function by InlA has been established (Lecuit et al., 2001, 2004), and it is suspected that traversal of the blood-brain barrier probably also requires InlA/E-cadherin interactions.”

“IpaB interacts with the hyaluronic receptor CD44 and mobilizes this host protein in cholesterol-rich lipid rafts, allowing the potential recruitment of other signaling molecules at the site of bacterial entry (Lafont et al., 2002).”

“…(the agents of enteric yersiniosis), YadA is the prototype of the new subfamily of trimeric autotransporters, in which three autotransporter subunits associate to form the functional pore (Cotter et al., 2005); YadA mediates adhesion to collagen, laminin, and fibronectin (Nummelin et al., 2004).”

“The murine pathogen Citrobacter rodentium has also acquired by horizontal gene transfer the LEE, which enables it to form pedestals (Deng et al., 2001).”

“…is the paradigm of the ‘‘chaperone/ usher’’ pathway (Figure 1A), in which the periplasmic chaperone PapD transports each of the pilus subunits to the outer membrane assembly platform/usher PapC, which in turn facilitates subunit translocation to the bacterial surface (Thanassi et al., 1998).”

“…(the agents of enteric yersiniosis), YadA is the prototype of the new subfamily of trimeric autotransporters, in which three autotransporter subunits associate to form the functional pore (Cotter et al., 2005); YadA mediates adhesion to collagen, laminin, and fibronectin (Nummelin et al., 2004).”

“…in vitro (Li and Walker, 1998; Uchiyama 2003). rOmpB, which belongs to a family of autotransporters in Gram-negative bacteria, has been recently described as the bacterial ligand of a R. conorii receptor on target cells, Ku70, a component of the DNA-dependent protein kinase (Martinez et al., 2005).”

“Using molecular biology tools and genomics, it has been established that these microorganisms belong to the same bacterial cluster as E. coli , having acquired by horizontaltransfersimilargenesthatenablethemtoinvade and colonize target cells in specific ways (Parsot 2005).”

“In the case of S. enterica , it was determined that the translocation process is extremely fast, and the pool of stocked intrabacterial SipA can be completely injected between 100–600 s (Schlumberger et al., 2005).”

“PI3K then is involved in activation of Rac and induction of actin polymerization through the activity of WAVE and the Arp2/3 complex (Bierne et al., 2001, 2005).”

“The presence of plasma membrane microdomains known as lipid rafts, which function as platforms for recruitment of signaling molecules, are also required for invasion of target cells by the FimH-dependent pathway (Duncan et al., 2004).”

“EPEC Tir has a GTPase activating protein (GAP) activity that has been implicated in the down-regulation of pedestals formation (Kenny et al., 2002).”

“…phosphorylation of cortactin, a molecule involved in the recruitment of the Arp2/3 complex for actin polymerization; actin binding proteins such as vinculin, tensin, and zyxin are also recruited to the bacterial attachment site, promoting S. aureus internalization (Agerer et al., 2005).”

“…with chaperons before actual contact with target cells; kinetics of secretion of IpaB and IpaC are rapid and highly concurrent as revealed by live-cell imaging, indicating that quick ejection of these effectors is the rate-limiting step for the invasion process (Enninga et al., 2005) (Figure 5A).”

“Integrity of lipids rafts is also required for the InlB-dependent pathway; however, in contrast to the InlA/E-cadherin case, it is not the initial interaction be-tween InlB and Met that is favored by lipid rafts, but the signaling downstream of PI3K activation (Seveau et al., 2004).”

“Cdc42 and RhoA are also required for the FimH-dependent cell invasion process by UPEC (Martinez and Hultgren, 2002).”

“In Neisseria spp., it has been shown that the inner membrane ATPase PilT is involved in type IV pilus retraction (Wolfgang et al., 1998).”

“S . flexneri also induces actin depo-lymerization by activating the actin binding protein vinculin via the TTSS effector IpaA (Bourdet-Sicard et al., 1999), allowing recovery of the plasma membrane architecture after invasion.”

“The final quaternary structure is acquired outside the bacterial outer membrane (vi) (adapted from Sauer et al., 2000).”

“The Abl/Arg tyrosine kinases phosphorylate the molecular adaptor Crk, which presumably activates a GEF for Cdc42 and Rac1 (Burton et al., 2003).”

“Most other Opa proteins can bind CEACAMs, inducing not only bacterial invasion but also increased adhesion of infected cells to the ECM, counteracting the exfoliation of epithelial cells that normally takes place as an innate immune response against infection (Muenzner et al., 2005).”

“…drives actin polymerization and actin filament bundling (Hayward and Kor-onakis, 1999), while SipA antagonizes the functions of the actin depolymerizing factor cofilin and of the actin filament severing protein gelsolin, preventing disassembly of formed actin fibers (McGhie et al., 2004)(Figure 4B).”

“Activation of Src and FAK, two important events strongly associated with b 1-integrin activation, are also detected during invasion of target cells by R. conorii ; Cdc42 (but not Rac1), PI3K, cortactin and the Arp2/3 complex are also molecules required for entry (Martinez and Cossart, 2004).”

“Originally it was proposed that a single autotrans-porter was required for its own transport, but it has been suggested recently that several autotransporters may associate to generate a pore that can support the transport of even folded passenger domains (Veiga et al., 2002).”

“A minor subunit of the Neisseria spp. type IV pili, PilV, has also been described as mediating bacterial adhesion to epithelial cells (Winther-Larsen et al., 2001).”

“Indirect stimulation of actin polymerization via Rac1 and WAVE2 is orchestrated via the TTSS effector VirA, which also inhibits microtubule polymerization (Yoshida et al., 2002) (Figure 4C).”

“The focal adhesion kinase (FAK) or the Src family of kinases are often associated with physiological integrin-mediated signaling, and Y. pseudotuberculosis subverts the function of these proteins to invade nonphagocytic cells (Alrutz and Isberg, 1998; Bruce-Staskal et al., 2002).”

“…al., 2003); some Afa/Dr molecules can additionally interact with CEACAMs, triggering activation of Cdc42 and the subsequent phosphorylation of the actin binding proteins ezrin, radixin, and moesin, leading to the formation of elongated microvilli underlying the adhering DAEC (Berger et al., 2004).”

“Indirect stimulation of actin polymerization via Rac1 and WAVE2 is orchestrated via the TTSS effector VirA, which also inhibits microtubule polymerization (Yoshida et al., 2002) (Figure 4C).”

“EPEC Tir can also trigger Nck-independent pedestal formation, which depends on tyrosine-474 and tyrosine-454 phosphorylation, recruiting a still unknown phosphotyrosine binding adaptor involved in N-WASP and Arp2/3 binding (Campellone and Leong, 2005).”

“…the complex behavior of some pathogens, by combining information issued from tissue culture assays and in vivo studies, some concepts in the field need to be reconsidered—in particular, the strict distinction be-tween extracellular versus intracellular bacteria (see for example Oh et al., 2005).”

“In the case of EPEC, Tir is phosphorylated by host kinases such as Fyn and Abl (Phillips et al., 2004; Swimm et al., 2004) on tyrosine-474 and is involved in the recruitment of the host adaptor molecule Nck, which in turn recruits the Wiskott-Aldrich syndrome protein (N-WASP) and the actin-related…”

“PilT is also required for force-dependent pilus elongation, suggesting that bacteria can modulate interaction with surfaces by controlling tension on their pili (Maier et al., 2004).”

“…several members of this family have now been shown to be assembled into true fimbrial structures: the sequence of the adhesin dictates whether or not it will be assembled into fimbriae, and genetically switching the genes encoding the adhesins switches the adhesin type (Anderson et al., 2004).”

“For example, the major adhesins SfbI of S. pyogenes and FnBP-A of S. aureus bind ECM-associated fibronectin and induce the clustering of fibronectin bound integrin receptors, triggering intracellular signaling (Ozeri et al., 2001; Joh et al., 1999; see below).”

“Engagement of E-cadherin by InlA leads to recruitment of two catenins to the bacterial internalization site: b -catenin binds to the C-terminal cytoplasmic domain of E-caderin, and recruits at the same time a -catenin (Lecuit et al., 2000) (Figure 4D).”

“…including necrotizing fasciitis), which presents more than twelve fibronectin and collagen binding proteins, some of them displaying additional enzymatic activities such as serine protease activity in the case of ScpA or lipoproteinase activity in the case of SfbII (Kreikemeyer et al., 2004).”

“Crk also recruits cortactin, which is phosphorylated by Src and is implicated in the Arp2/3-dependent actin nucleation at the bacterial internalization site (Bougneres et al., 2004).”

“PI3K then is involved in activation of Rac and induction of actin polymerization through the activity of WAVE and the Arp2/3 complex (Bierne et al., 2001, 2005).”

“…the bacterial entry site of the phosphatidylinositol-phosphate-5-kinase I a , inducing the local production of phosphatidylinositol-4,5-biphosphate (Wong and Isberg, 2003), an important second messenger affecting the subcellular localization and activation of actin-regulating molecules…”

“The unconventional myosin VIIA and its ligand vezatin are also required for the InlA-mediated entry of L. monocytogenes , probably generating the tension required for internalization of engulfed bacteria (Sousa et al., 2004).”

“Nevertheless, type IV piliated Neisseria spp. are able to induce several activities including CD46 tyrosine phosphorylation, CD46 redistribution under signaling bacteria and release of CD46-enriched host membrane vesicles (Gill et al., 2005; Lee et al., 2005).”

“…structure compared to V. cholerae TcpA; nevertheless, EPEC and V. cholerae type IV pili have virtually similar helical organization, suggesting that evolutionary forces contribute to diversifica-tion in pilin structure while pilus structure and function are maintained (Ramboarina et al., 2005).”

“EPEC type IV bundle-forming pili, for example, are required for initial bacterial attachment to brush border cells as a prelude for the ‘‘attaching and effacing’’ phenotype (Tobe and Sasakawa 2002) (see below).”

“Cdc42 and RhoA are also required for the FimH-dependent cell invasion process by UPEC (Martinez and Hultgren, 2002).”

“In the case of S. flexneri , the translocon components IpaB and IpaC are homologous (although not identical in structure and function) to S. enterica SipB and SipC, and IpaC nucleates the formation of actin filaments beneath invading bacteria as SipC does (Kueltzo et al., 2003).”

“In the case of Neisseria spp., PilC-mediated adhesion to host cells via recognition of the complement regulator CD46 has been reported (Kallstrom et al., 1997), but recent studies suggest that the PilC ligand is a still undefined protein (Kirchner and Meyer, 2005).”

“InlB, thus, seems to exploit unexpectedly the normal trafficking of its receptor to promote invasion (Li et al., 2005).”

“PapD binds pilus sub-units to prevent their aggregation at the wrong time in the periplasmic space and catalyzes subunits folding to prime them for assembly (Bann et al., 2004).”

“…been described as putative adhesins favoring respectively R. conorii and R. japonica attachment to epithelial cells in vitro (Li and Walker, 1998; Uchiyama 2003). rOmpB, which belongs to a family of autotransporters in Gram-negative bacteria, has been recently described as the bacterial ligand…”

“Nevertheless, type IV piliated Neisseria spp. are able to induce several activities including CD46 tyrosine phosphorylation, CD46 redistribution under signaling bacteria and release of CD46-enriched host membrane vesicles (Gill et al., 2005; Lee et al., 2005).”

“P. aeruginosa type IV pili are the main adhesive organelles recognizing the disaccharide b -GalNAc(1-4) b Gal on epithelial cells asialo-GM1 and -GM2 gangliosides (Suh et al., 2001).”

“The prevailing paradigm has remained that M. tuberculosis reside in the endocytic system (Orme, 2004; Vergne et al., 2004; Russell et al., 2002; Kang et al., 2005; Russell, 2001; Pizarro-Cerda and Cossart, 2006).”

“Invasive bacterial pathogens use specific virulence factors that mediate efficient entry into mammalian cells where they can evade some immune mechanisms, such as complement- and antibody-mediated killing, and establish a replicative nich”

“By themselves, bacteria have a diverse virulence arsenal ranging from surface proteins to appendages (pili or fimbriae) that enables them to adhere to epithelial cells, facilitating colonization and infection 116 .”

“158 Pili, which are polymeric hair-like organelles protruding from the surface of bacteria, 159 represent a first class of structures involved in the binding of bacteria to host cells [30],[31].”

“For many microbial pathogens, invasion of host cells is critical for the initiation and maintenance of infection, and many of these organisms have more than one mechanism for inducing their own uptake by host cells [46].”

“Biofilm infections constitute a number of clinical challenges, including disease, chronic inflammation, impaired wound healing, rapidly acquired antibiotic resistance and the spread of infectious emboli.(34,36,48) Infections related with biomaterial in orthopedic applications lead to a condition of osteomyelitis with…”

“UPEC strains possess an impressive repertoire of adhesins that enable the bacteria to aggregate and adhere to the cellular surfaces [34, 57, 62, 69, 104].”

“This is particularly well illustrated by the capacity of bacteria such as Listeria , Salmonella and Shigella to trigger their own uptake into cells that are normally non-phagocyti”

“Many pathogenic bacteria multiply extracellularly, but it is increasingly recognized that many bacteria that were long considered extracellular can also reside, replicate, or persist inside cells (Pizarro-Cerda and Cossart 2006).”

“The mechanisms by which bacteria invade these cells have been a subject of intense investigation for many years (reviewed in [1]).”

“coli O157:H7 infection depends on bacterial attachment and the deployment of a type III secretion system (encoded by the locus of enterocyte effacement), which acts as a molecular syringe to transmit bacterial effector proteins into the cytoplasm of host cells (32, 45).”

“In vivo, unlike for bacterial pathogens where mechanisms of epithelial entry are well characterized (Pizarro-Cerda and Cossart, 2006), the Received 18 March, 2007; revised 24 May, 2007; accepted 30 May, 2007.”

“Parasites, such as members of the apicomplexa group, can actively penetrate into host cells using actin-mediated forces [26].”

“Bacteria, on the other hand, cannot actively penetrate host cells, but have developed several strategies to cause uptake by induced endocytosis [25,26].”

“These bacteria use a specialized secretory apparatus, the type III secretion system (T3SS), to inject bacterial effector proteins into the host cytoplasm to modulate the host actin cytoskeleton, triggering massive polymerization of actin and membrane ruffling, resulting in bacterial internalization in a process simila…”

“UPEC strains possess an impressive repertoire of adhesins that enable them to aggregate and adhere to cellular surfaces (107, 137, 203, 235, 276).”

“Detailed information is reported by Pizarro-Cerdá and Cossart [10].”

“, that they use multiple adhesins to attach to enterocyte”

“In some Gram-negative pathogens, pili-mediated adhesion can lead to the host cell internalizing the bacteria (Pizarro-Cerda and Cossart, 2006).”

“In studies of pathogen–host interactions, the latter limitation can often be circumvented by monitoring the interaction at a later stage in the pathogenic process [i.e. cellular invasion and multiplication, dissemination and/or persistence (Sakarya & Oncu, 2003; Pizarro-Cerda & Cossart, 2006)].”

“The specific adhesive qualities of fimbriae are attributed to an adhesin tip protein homologu”

“Integrins can be used either as primary attachment receptors or as co-receptors in the entry process (Greber, 2002; Marsh and Helenius, 2006; Pizarro-Cerda and Cossart, 2006), and pathogen attachment triggers host-cell signaling pathways that follow binding of the endogenous ligand to integrins…”

“Protein-protein interactions play a central role for molecular pathogenesis of infectious diseases [3, 26 ].”

“…since it is a required step for the establishment of infection, which may be followed by colonization of tissues, and in some cases by bacterial invasion of host cells, followed by intracellular multiplication, dissemination to other tissues, or persistence (Pizarro-Cerda & Cossart, 2006).”

“…and suppressing antibacterial defence mechanisms (Christie et al., 2005; Guiney, 2005; Suparak et al., 2005; Grant et al., 2006; Gurlebeck et al., 2006; Pilatz et al., 2006; Pizarro-Cerda & Cossart, 2006; Schlumberger & Hardt, 2006; Angot et al., 2007; He et al., 2007; Ninio & Roy, 2007).”

“It is likely that these pili are involved in corynebacterial attachment to host tissues, as pilus-mediated adherence is a critical step in the establishment of infection by many Gramnegative pathogens (Pizarro-Cerda and Cossart, 2006).”

“SpT plays a role once bacterial internalization has taken place, inactivating the Rho GTPases, inhibiting actin polimerization, and assuring closure of the plasma membrane and recovery of the normal cellular architecture (Pizarro-Cerda and Cossart, 2006) .”

“developed distinct ways to modify the ECM (1, 36).”

“efficiently colonizes the mucosal tissue, in line with what is expected from pathogenic microorganisms, whose success in the infection largely depends on their ability to adhere to host cells and colonize host tissue [77].”

“The adhesion step is crucial for bringing dysbiosis to the host microbiota and colonizing and invading the host cells (Pizarro-Cerdá and Cossart, 2006).”

“emboli (Bryers, 2008; Hall-Stoodley et al., 2004; Pizarro-Cerdá and Cossart, 2006).”

“One mechanism employed by bacteria to evade the host innate immune response is escape into the cytoplasm to avoid lysosomal killing [60,112].”

“The integrin endo/exocytic cycle [25-27] suggests that there are, at least, three types of pathways associated with integrin internalization: 1/ clathrin-mediated endocytosis was described for αvβ5 integrins [28]; 2/ caveolae-mediated endocytosis for α2 integrins [29] and 3/ clathrin-caveolaeindependent endocytosis.”

“Bacteria are known to induce their entry by activating host receptors or by injecting effectors into the host cell cytosol [1,2,70].”

“Most gram-negative and grampositive bacterial pathogens produce fimbriae (Foster 2004; Odenbreit 2005; Pizarro-Cerdá and Cossart 2006).”

“cadherin [35], receptors on the IECs [18], or components of the extracellular matrix [36,37].”

“[44]).”

“PI3K is required for modifying the cytoskeleton dynamics, regulating membrane traffic, coordinating exocytic membrane insertion and pseudopod extension, which could be utilized by some pathogenic bacteria for entry into host cell [34-38].”

“Conclusions Adherence to specific host tissues is instrumental for many bacterial pathogens to mount successful colonization of humans (Pizarro-Cerda and Cossart, 2006).”

“They can be involved in a number of processes such as biofilm formation, surface attachment, and evasion of the host immune response [52].”

“In order to colonize their hosts, pathogenic bacteria must both evade the immune response and interact with host cells, often adhering to specific surface-localized molecules (Pizarro-Cerda and Cossart, 2006).”

“It is known that pathogenic bacteria have evolved a plethora of proteins to adhere to and invade host tissues and to resist host defenses (Pizarro-Cerda & Cossart, 2006).”

“A pilus is a long multi-subunit appendage with binding specificity at the terminal subunits, typically through FimH or PapG, for a specific receptor on the host cell surface [81, 82, 85, 86].”

“These specific interactions may also help determine the cell and tissue tropism of the bacteria (Finlay and Falkow, 1989; Boyle and Finlay, 2003; Pizarro-Cerda and Cossart, 2006).”

“Successful establishment of GAS infection requires adhesion to host cells, colonization and, in certain cases, cell invasion followed by intracellular multiplication, dissemination, and/or persistence (Pizarro-Cerdá and Cossart, 2006).”

“Invasive pathogens, like Shigella flexneri, Salmonella enterica and Listeria monocytogenes, force their uptake into non-phagocytic host cells via tightly controlled mechanisms like endocytosis, phagocytosis or macropinocytosis (Conner and Schmid, 2003; Pizarro-Cerda and Cossart, 2006).”

“…epithelial cells is mainly mediated by two bacterial surface protein members of the internalin family, namely internalin (InlA) and InlB, that use E-cadherin and Met as receptors, respectively, on the surface of host cells (Hamon et al. 2006; Pizarro-Cerda and Cossart 2006; Bonazzi et al. 2009).”

“V. chlorellavorus is the first recognised member of the Cyanobacteria with a predatory lifecycle and we predict that it is the first predator to use a conjugative type IV secretion system similar to Agrobacterium tumefaciens to invade its host.”

“Invasive pathogens induce their internalization through secreted proteins interfering with cytoskeleton machinery (for a review, see Pizarro-Cerda and Cossart, 2006).”

“This step generally depends on specific interactions of fimbriae or pili displayed on bacterial cell surfaces with distinct host cell receptors, which govern the bacterial host range and sites of infection (27, 34).”

“monocytogenes, internalin B, which enables Listeria to enter and survive within epithelial cells via interaction with three different epithelial membrane receptors (4, 19).”