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1.
Adhesion to host cells is the first step in the virulence cycle of any pathogen. In Gram‐negative bacteria, adhesion is mediated, among other virulence factors such as the lipopolysaccharides, by specific outer‐membrane proteins generally termed adhesins that belong to a wide variety of families and have different evolutionary origins. In Brucella, a widespread zoonotic pathogen of animal and human health concern, adhesion is central as it may determine the intracellular fate of the bacterium, an essential stage in its pathogenesis. In the present paper, we further characterised a genomic locus that we have previously reported encodes an adhesin (BigA) with a bacterial immunoglobulin‐like domain (BIg‐like). We found that this region encodes a second adhesin, which we have named BigB; and PalA, a periplasmic protein necessary for the proper display in the outer membrane of BigA and BigB. Deletion of bigB or palA diminishes the adhesion of the bacterium and overexpression of BigB dramatically increases it. Incubation of cells with the recombinant BIg‐like domain of BigB induced important cytoskeletal rearrangements and affected the focal adhesion sites indicating that the adhesin targets cell–cell or cell–matrix proteins. We additionally show that PalA has a periplasmic localisation and is completely necessary for the proper display of BigA and BigB, probably avoiding their aggregation and facilitating their transport to the outer membrane. Our results indicate that this genomic island is entirely devoted to the adhesion of Brucella to host cells. 相似文献
2.
The novel chlamydial adhesin CPn0473 mediates the lipid raft‐dependent uptake of Chlamydia pneumoniae
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Chlamydiae are Gram‐negative, obligate intracellular pathogens that pose a serious threat to public health worldwide. Chlamydial surface molecules are essential for host cell invasion. The first interaction with the host cell is thereby accomplished by the Outer membrane complex protein B (OmcB) binding to heparan sulfate moieties on the host cell surface, followed by the interaction of the chlamydial polymorphic membrane proteins (Pmps) with host cell receptors. Specifically, the interaction of the Pmp21 adhesin and invasin with its human interaction partner, the epidermal growth factor receptor, results in receptor activation, down‐stream signalling and finally internalization of the bacteria. Blocking both, the OmcB and Pmp21 adhesion pathways, did not completely abolish infection, suggesting the presence of additional factors relevant for host cell invasion. Here, we show that the novel surface protein CPn0473 of Chlamydia pneumoniae contributes to the binding and invasion of infectious chlamydial particles. CPn0473 is expressed late in the infection cycle and located on the infectious chlamydial cell surface. Soluble recombinant CPn0473 as well as rCPn0473‐coupled fluorescent latex beads adhere to human epithelial HEp‐2 cells. Interestingly, in classical infection blocking experiments pretreatment of HEp‐2 cells with rCPn0473 does not attenuate adhesion but promotes dose‐dependently internalization by C. pneumoniae suggesting an unusual mode of action for this adhesin. This CPn0473‐dependent promotion of infection by C. pneumoniae depends on two different domains within the protein and requires intact lipid rafts. Thus, inhibition of the interaction of CPn0473 with the host cell could provide a way to reduce the virulence of C. pneumoniae. 相似文献
3.
Cesar M. Valencia‐Gallardo Nathalie Carayol Guy Tran Van Nhieu 《Cellular microbiology》2015,17(2):174-182
The actin cytoskeleton is key to the barrier function of epithelial cells, by permitting the establishment and maintenance of cell–cell junctions and cell adhesion to the basal matrix. Actin exists under monomeric and polymerized filamentous form and its polymerization following activation of nucleation promoting factors generates pushing forces, required to propel intracellular microorganisms in the host cell cytosol or for the formation of cell extensions that engulf bacteria. Actin filaments can associate with adhesion receptors at the plasma membrane via cytoskeletal linkers. Membrane anchored to actin filaments are then subjected to the retrograde flow that may pull membrane‐bound bacteria inside the cell. To induce its internalization by normally non‐phagocytic cells, bacteria need to establish adhesive contacts and trick the cell into apply pulling forces, and/or to generate protrusive forces that deform the membrane surrounding its contact site. In this review, we will focus on recent findings on actin cytoskeleton reorganization within epithelial cells during invasion and cell‐to‐cell spreading by the enteroinvasive pathogen Shigella, the causative agent of bacillary dysentery. 相似文献
4.
Verónica Ruiz-Ranwez Diana M. Posadas Silvia M. Estein Patricia L. Abdian Fernando A. Martin Angeles Zorreguieta 《PloS one》2013,8(11)
The adhesion of bacterial pathogens to host cells is an event that determines infection, and ultimately invasion and intracellular multiplication. Several evidences have recently shown that this rule is also truth for the intracellular pathogen Brucella. Brucella suis displays the unipolar BmaC and BtaE adhesins, which belong to the monomeric and trimeric autotransporter (TA) families, respectively. It was previously shown that these adhesins are involved in bacterial adhesion to host cells and components of the extracellular matrix (ECM). In this work we describe the role of a new member of the TA family of B. suis (named BtaF) in the adhesive properties of the bacterial surface. BtaF conferred the bacteria that carried it a promiscuous adhesiveness to various ECM components and the ability to attach to an abiotic surface. Furthermore, BtaF was found to participate in bacterial adhesion to epithelial cells and was required for full virulence in mice. Similar to BmaC and BtaE, the BtaF adhesin was expressed in a small subpopulation of bacteria, and in all cases, it was detected at the new pole generated after cell division. Interestingly, BtaF was also implicated in the resistance of B. suis to porcine serum. Our findings emphasize the impact of TAs in the Brucella lifecycle. 相似文献
5.
The Chlamydia trachomatis Ctad1 invasin exploits the human integrin β1 receptor for host cell entry
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Infection of human cells by the obligate intracellular bacterium Chlamydia trachomatis requires adhesion and internalization of the infectious elementary body (EB). This highly complex process is poorly understood. Here, we characterize Ctad1 (CT017) as a new adhesin and invasin from C. trachomatis serovar E. Recombinant Ctad1 (rCtad1) binds to human cells via two bacterial SH3 domains located in its N‐terminal half. Pre‐incubation of host cells with rCtad1 reduces subsequent adhesion and infectivity of bacteria. Interestingly, protein‐coated latex beads revealed Ctad1 being an invasin. rCtad1 interacts with the integrin β1 subunit on human epithelial cells, and induces clustering of integrins at EB attachment sites. Receptor activation induces ERK1/2 phosphorylation. Accordingly, rCtad1 binding to integrin β1‐negative cells is significantly impaired, as is the chlamydial infection. Thus interaction of C. trachomatis Ctad1 with integrin β1 mediates EB adhesion and induces signaling processes that promote host‐cell invasion. 相似文献
6.
In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross‐talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial‐mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins. 相似文献
7.
Erika Garay Genaro Patiño‐López Socorro Islas Lourdes Alarcón Elsy Canche‐Pool Ricardo Valle‐Rios Oscar Medina‐Contreras Giovana Granados Bibiana Chávez‐Munguía Eusebio Juaristi Vianney Ortiz‐Navarrete Lorenza González‐Mariscal 《Journal of cellular biochemistry》2010,111(1):111-122
Class I‐restricted T cell associated molecule (CRTAM) is a member of the immunoglobulin superfamily that complies with the structural characteristics of the JAM family of proteins and is phylogenetically more closely related to nectin‐like proteins. Here we demonstrate for the first time, that CRTAM is expressed in epithelial cells along the lateral membrane and is important for early cell–cell contacts and cell–substrate interactions. CRTAM is sensitive to intermediate filament disruption and treatment of monolayers with soluble CRTAM enhances cell–cell dissociation and lowers transepithelial electrical resistance. Incubation of newly plated cells with anti‐CRTAM antibody decreases the formation of cell aggregates and promotes cell detachment. Co‐cultures of epithelial cells and fibroblasts that lack CRTAM expression and in vitro binding assays, demonstrate the participation of CRTAM in homotypic and heterotypic trans‐interactions. Hence we conclude that CRTAM is a molecule involved in epithelial cell adhesion. J. Cell. Biochem. 111: 111–122, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
8.
Colonisation of the body surface of healthy subjects by Staphylococcus aureus is mostly harmless because the immune system limits bacterial growth. Under as yet unknown circumstances, however, previously commensal bacteria may become pathogenic by rapid proliferation and density‐dependent generation of virulence factors that negatively affect the surrounding eukaryotic host cells. One of the most problematic virulence factors of Staphylococcus aureus is alpha‐toxin (hemolysin A, Hla). This toxin forms transmembrane pores in the plasma membranes of eukaryotic host cells. The inner diameter of the pore allows ions and small organic molecules to pass from the extracellular space to the cytosol or vice versa. The resulting dissipation of ion gradients as well as loss of energy‐rich molecules like ATP from the cells heavily disturbs host cell functions and signal transduction processes. In epithelial cells, these changes severely affect the polarized phenotype of the epithelial cells by restructuring of the actin cytoskeleton, inducing changes in cell shape and loosening cell‐cell adhesion which ultimately compromises the barrier function of the cell sheet. These effects of alpha‐toxin may provide an explanation why it is particularly Staphylococcus aureus that is involved in the onset of many cases of lung infections (pneumonia). 相似文献
9.
Yannick D. Benoit Carine Lussier Pierre‐Alexandre Ducharme Sophie Sivret Lynn M. Schnapp Nuria Basora Jean‐François Beaulieu 《Biology of the cell / under the auspices of the European Cell Biology Organization》2009,101(12):695-708
Background. Integrins are transmembrane αβ heterodimer receptors that function as structural and functional bridges between the cytoskeleton and ECM (extracellular matrix) molecules. The RGD (arginine‐glycine‐aspartate tripeptide motif)‐dependent integrin α8β1 has been shown to be involved in various cell functions in neuronal and mesenchymal‐derived cell types. Its role in epithelial cells remains unknown. Results. Integrin α8β1 was found to be expressed in the crypt cell population of the human intestine but was absent from differentiating and mature epithelial cells of the villus. The function of α8β1 in epithelial crypt cells was investigated at the cellular level using normal HIECs (human intestinal epithelial cells). Specific knockdown of α8 subunit expression using an shRNA (small‐hairpin RNA) approach showed that α8β1 plays important roles in RGD‐dependent cell adhesion, migration and proliferation via a RhoA/ROCK (Rho‐associated kinase)‐dependent mechanism as demonstrated by active RhoA quantification and pharmacological inhibition of ROCK. Moreover, loss of α8β1, through RhoA/ROCK, impairs FA (focal adhesion) complex integrity as demonstrated by faulty vinculin recruitment. Conclusions. Integrin α8β1 is expressed in epithelial cells. In intestinal crypt cells, α8β1 is closely involved in the regulation of adhesion, migration and cell proliferation via a predominant RhoA/ROCK‐dependent mechanism. These results suggest an important role for this integrin in intestinal crypt cell homoeostasis. 相似文献
10.
Helicobacter pylori adhesins: review and perspectives 总被引:7,自引:0,他引:7
It is highly unlikely that chronic infection with H. pylori could occur in the absence of adhesin–host cell interactions. Also, there is no evidence that any of the serious outcomes of H. pylori infection such as gastric and duodenal ulcers, gastric cancer or mucosa‐associated lymphoid tissue (MALT) lymphoma could occur without prior colonization of the gastric epithelium mediated by H. pylori adhesins. H. pylori is highly adaptable, as evidenced by the fact that it can occupy a single host for decades. An important facet of this adaptability is its ability to physically interact with various types of host cells and also with host mucins and extracellular matrix proteins using a number of different adhesins displaying a variety of unique receptor specificities. Thus it is highly unlikely that any one particular H. pylori adhesin will ever be proven responsible for a particular outcome such as duodenal ulcer, MALT lymphoma, or adenocarcinoma. Also, while the search for additional H. pylori adhesins should and certainly will continue, we suggest that the scope of this effort should be expanded to include investigations into the patterns of expression and interaction between individual outer membrane proteins. Which of the numerous H. pylori outer membrane proteins (OMPs) actually function as adhesins (i.e., have receptor‐binding sites) and which OMPs are simply necessary for optimal display of the adhesive OMPs? There are many other important questions about H. pylori adhesins waiting to be answered. For example, which adhesins are responsible for loose adherence to host cells and which adhesins are responsible for intimate, or membrane‐to‐membrane, adherence, and do these adhesins normally work in concert or in a sequential fashion? Also, is a specific type of adhesin necessary for type IV protein translocation into host cells and, if so, is adhesin expression coregulated with the effector protein export? 相似文献
11.
Salmonella typhimurium is an invasive Gram‐negative enteric bacterium, which causes salmonellosis, a type of gastroenteritis in humans and typhoid‐like symptoms in mice. Upon entering through the contaminated food and water, S. typhimurium adheres, colonises, and invades intestinal epithelial cells (IECs) of the small intestine. In this study, we have shown that upon deletion of the outer membrane protein OmpV, there is a significant decrease in adherence of S. typhimurium to the IECs, indicating that OmpV is an important adhesin of S. typhimurium. Further, our study showed that OmpV binds to the extracellular matrix component fibronectin and signals through α1β1 integrin receptor on the IECs and OmpV‐mediated activation of α1β1, resulting in the activation of focal adhesion kinase and F‐actin modulation. Actin modulation is crucial for bacterial invasion. To the best of our knowledge, this is the first report of an adhesin mediated its effect through integrin in S. typhimurium. Further, we have observed a decrease in pathogenicity in terms of increased LD50 dose, lesser bacterial numbers in stool, and less colonisation of bacteria in different organs of mice infected with Δompv mutant compared with the wild‐type bacteria, thus confirming the crucial role of OmpV in the pathogenesis of S. typhimurium. 相似文献
12.
Becherelli M Manetti AG Buccato S Viciani E Ciucchi L Mollica G Grandi G Margarit I 《Molecular microbiology》2012,83(5):1035-1047
Gram‐positive pili are known to play a role in bacterial adhesion to epithelial cells and in the formation of biofilm microbial communities. In the present study we undertook the functional characterization of the pilus ancillary protein 1 (AP1_M6) from Streptococcus pyogenes isolates expressing the FCT‐1 pilus variant, known to be strong biofilm formers. Cell binding and biofilm formation assays using S. pyogenes in‐frame deletion mutants, Lactococcus expressing heterologous FCT‐1 pili and purified recombinant AP1_M6, indicated that this pilin is a strong cell adhesin that is also involved in bacterial biofilm formation. Moreover, we show that AP1_M6 establishes homophilic interactions that mediate inter‐bacterial contact, possibly promoting bacterial colonization of target epithelial cells in the form of three‐dimensional microcolonies. Finally, AP1_M6 knockout mutants were less virulent in mice, indicating that this protein is also implicated in GAS systemic infection. 相似文献
13.
Outer membrane vesicles (OMVs) released by some Gram-negative bacteria have been shown to exert immunomodulatory effects that favor the establishment of the infection. The aim of the present study was to assess the interaction of OMVs from Brucella abortus with human epithelial cells (HeLa) and monocytes (THP-1), and the potential immunomodulatory effects they may exert. Using confocal microscopy and flow cytometry, FITC-labeled OMVs were shown to be internalized by both cell types. Internalization was shown to be partially mediated by clathrin-mediated endocytosis. Pretreatment of THP-1 cells with Brucella OMVs inhibited some cytokine responses (TNF-α and IL-8) to E. coli LPS, Pam3Cys or flagellin (TLR4, TLR2 and TLR5 agonists, respectively). Similarly, pretreatment with Brucella OMVs inhibited the cytokine response of THP-1 cells to B. abortus infection. Treatment of THP-1 cells with OMVs during IFN-γ stimulation reduced significantly the inducing effect of this cytokine on MHC-II expression. OMVs induced a dose-dependent increase of ICAM-1 expression on THP-1 cells and an increased adhesion of these cells to human endothelial cells. The addition of OMVs to THP-1 cultures before the incubation with live B. abortus resulted in increased numbers of adhered and internalized bacteria as compared to cells not treated with OMVs. Overall, these results suggest that OMVs from B. abortus exert cellular effects that promote the internalization of these bacteria by human monocytes, but also downregulate the innate immune response of these cells to Brucella infection. These effects may favor the persistence of Brucella within host cells. 相似文献
14.
ICAM1 and fibrinogen-γ are increased in uterine epithelial cells at the time of implantation in rats
Uterine epithelial cells transform into a receptive state to adhere to an implanting blastocyst. Part of this transformation includes the apical concentration of cell adhesion molecules at the time of implantation. This study, for the first time, investigates the expression of ICAM1 and fibrinogen‐γ (FGG) in uterine epithelial cells during normal pregnancy, pseudopregnancy and in hormone‐treated rats. An increase (P < 0.05) in ICAM1 was seen at the apical membrane of uterine epithelial cells at the time of implantation compared with day 1 of pregnancy. ICAM1 was also increased (P < 0.05) on day 6 of pseudopregnancy as well as in ovariectomized rats treated with progesterone plus oestrogen. These results show that ICAM1 up‐regulation at the time of implantation is under the control of progesterone, and is not dependent on cytokine release from the blastocyst or in semen. FGG dimerization increased (P < 0.05) on day 6 of pregnancy compared with day 1, and was not up‐regulated in day 6 pseudopregnant animals, suggesting this increase is dependent on a developing blastocyst. The presence of ICAM1 and FGG in the uterine epithelium at the time of implantation in the rat is similar to that seen in lymphocyte–endothelium adhesion, and we suggest a similar mechanism in embryo–uterine epithelium adhesion is utilized. Mol. Reprod. Dev. 78:318–327, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
15.
Yersinia enterocolitica exploits different pathways to accomplish adhesion and toxin injection into host cells
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Birgit Keller Melanie Mühlenkamp Eva Deuschle Alexandra Siegfried Sara Mössner Jessica Schade Tanja Griesinger Nenad Katava Christina Braunsdorf Birgit Fehrenbacher Luisa F. Jiménez‐Soto Martin Schaller Rainer Haas Harald Genth Saverio F. Retta Hannelore Meyer Ralph T. Böttcher Roy Zent Monika Schütz Ingo B. Autenrieth Erwin Bohn 《Cellular microbiology》2015,17(8):1179-1204
The current paradigm suggests that Yersinia enterocolitica (Ye) adheres to host cells via the outer membrane proteins Yersinia adhesin A (YadA) or invasin (Inv) to facilitate injection of Yops by the type III secretion system. In this process Inv binds directly to β1 integrins of host cells while YadA may bind indirectly via extracellular matrix proteins to β1 integrins. Here we challenged this paradigm and investigated the requirements for Yop injection. We demonstrate that Inv‐ but not YadA‐mediated adhesion depends on β1 integrin binding and activation, and that tight adhesion is a prerequisite for Yop injection. By means of novel transgenic cell lines, shRNA approaches and RGD peptides, we found that YadA, in contrast to Inv, may use a broad host cell receptor repertoire for host cell adhesion. In the absence of β1 integrins, YadA mediates Yop injection by interaction with αV integrins in cooperation with yet unknown cofactors expressed by epithelial cells, but not fibroblasts. Electron microscopic and flow chamber studies revealed that a defined intimate contact area between Ye and host cells resulting in adhesion forces resisting shear stress is required for Yop injection. Thus, the indirect binding of YadA to a broad extracellular matrix (ECM) binding host cell receptor repertoire of different cell types makes YadA a versatile tool to ensure Yop injection. In conclusion, given the differential expression of the outer membrane proteins Inv and YadA in the course of Ye infection and differential expression of integrins by various host cell populations, the data demonstrate that Ye is flexibly armed to accomplish Yop injection in different host cell types, a central event in its immune evasion strategy. 相似文献
16.
Combinatorial control of adhesion of Brucella abortus 2308 to host cells by transcriptional rewiring of the trimeric autotransporter btaE gene
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Rodrigo Sieira Magalí G. Bialer Mara S. Roset Verónica Ruiz‐Ranwez Tomás Langer Gastón M. Arocena Estefanía Mancini Angeles Zorreguieta 《Molecular microbiology》2017,103(3):553-565
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Antimicrobial peptides (AMPs) constitute an essential part of the innate immune defence. Pathogenic bacteria have evolved numerous strategies to withstand AMP‐mediated killing. The influence of host epithelia on bacterial AMP resistance is, however, still largely unknown. We found that adhesion to pharyngeal epithelial cells protected Neisseria meningitidis, a leading cause of meningitis and sepsis, from the human cathelicidin LL‐37, the cationic model amphipathic peptide (MAP) and the peptaibol alamethicin, but not from polymyxin B. Adhesion to primary airway epithelia resulted in a similar increase in LL‐37 resistance. The inhibition of selective host cell signalling mediated by RhoA and Cdc42 was found to abolish the adhesion‐induced LL‐37 resistance by a mechanism unrelated to the actin cytoskeleton. Moreover, N. meningitidis triggered the formation of cholesterol‐rich membrane microdomains in pharyngeal epithelial cells, and host cell cholesterol proved to be essential for adhesion‐induced resistance. Our data highlight the importance of Rho GTPase‐dependent host cell signalling for meningococcal AMP resistance. These results indicate that N. meningitidis selectively exploits the epithelial microenvironment in order to protect itself from LL‐37. 相似文献
20.
Wilrun Mittelstädt Kathrin Blank Erik Sommer Gabriele Malengo Daniela Döhler Anna Lange Viktor Sourjik Michael Hensel Roman G. Gerlach 《Cellular microbiology》2014,16(2):161-178
The giant non‐fimbrial adhesin SiiE is essential to establish intimate contact between Salmonella enterica and the apical surface of polarized epithelial cells. SiiE is secreted by a type I secretion system (T1SS) encoded by Salmonella Pathogenicity Island 4 (SPI4). We identified SiiA and SiiB as two regulatory proteins encoded by SPI4. Mutant strains in siiA or siiB still secrete SiiE, but are highly reduced in adhesion to, and invasion of polarized cells. SiiA and SiiB are inner membrane proteins with one and three transmembrane (TM) helices respectively. TM2 and TM3 of SiiB are similar to members of the ExbB/TolQ family, while the TM of SiiA is similar to MotB and a conserved aspartate residue in this TM is essential for SPI4‐encoded T1SS function. Co‐immunoprecipitation, bacterial two‐hybrid and FRET demonstrate homo‐ and heterotypic protein interactions for SiiA and SiiB. SiiB, but not SiiA also interacts with the SPI4‐T1SS ATPase SiiF. The integrity of the Walker A box in SiiF was required for SiiB–SiiF interactionand SiiF dimer formation. Based on these data, we describe SiiA and SiiB as new, exclusively virulence‐associated members of the Mot/Exb/Tol family of membrane proteins. Both proteins are involved in a novel mechanism of controlling SPI4‐T1SS‐dependent adhesion, most likely by formation of a proton‐conducting channel. 相似文献