1887

Abstract

Non-typable (NTHi) is a common commensal of the human nasopharynx, but causes opportunistic infection when the respiratory tract is compromised by infection or disease. The ability of NTHi to invade epithelial cells has been described, but the underlying molecular mechanisms are poorly characterized. We previously determined that NTHi promotes phosphorylation of the serine-threonine kinase Akt in A549 human lung epithelial cells, and that Akt phosphorylation and NTHi cell invasion are prevented by inhibition of phosphoinositide 3-kinase (PI3K). Because PI3K-Akt signalling is associated with several host cell networks, the purpose of the current study was to identify eukaryotic molecules important for NTHi epithelial invasion. We found that inhibition of Akt activity reduced NTHi internalization; differently, bacterial entry was increased by phospholipase Cγ1 inhibition but was not affected by protein kinase inhibition. We also found that α5 and β1 integrins, and the tyrosine kinases focal adhesion kinase and Src, are important for NTHi A549 cell invasion. NTHi internalization was shown to be favoured by activation of Rac1 guanosine triphosphatase (GTPase), together with the guanine nucleotide exchange factor Vav2 and the effector Pak1. Also, Pak1 might be associated with inactivation of the microtubule destabilizing agent Op18/stathmin, to facilitate microtubule polymerization and NTHi entry. Conversely, inhibition of RhoA GTPase and its effector ROCK increased the number of internalized bacteria. Src and Rac1 were found to be important for NTHi-triggered Akt phosphorylation. An increase in host cyclic AMP reduced bacterial entry, which was linked to protein kinase A. These findings suggest that NTHi finely manipulates host signalling molecules to invade respiratory epithelial cells.

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2012-09-01
2024-03-28
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References

  1. Agarwal V., Asmat T. M., Dierdorf N. I., Hauck C. R., Hammerschmidt S. ( 2010). Polymeric immunoglobulin receptor-mediated invasion of Streptococcus pneumoniae into host cells requires a coordinate signaling of SRC family of protein-tyrosine kinases, ERK, and c-Jun N-terminal kinase. J Biol Chem 285:35615–35623 [View Article][PubMed]
    [Google Scholar]
  2. Agerer F., Michel A., Ohlsen K., Hauck C. R. ( 2003). Integrin-mediated invasion of Staphylococcus aureus into human cells requires Src family protein-tyrosine kinases. J Biol Chem 278:42524–42531 [View Article][PubMed]
    [Google Scholar]
  3. Agerer F., Lux S., Michel A., Rohde M., Ohlsen K., Hauck C. R. ( 2005). Cellular invasion by Staphylococcus aureus reveals a functional link between focal adhesion kinase and cortactin in integrin-mediated internalisation. J Cell Sci 118:2189–2200 [View Article][PubMed]
    [Google Scholar]
  4. Ahrén I. L., Williams D. L., Rice P. J., Forsgren A., Riesbeck K. ( 2001). The importance of a β-glucan receptor in the nonopsonic entry of nontypeable Haemophilus influenzae into human monocytic and epithelial cells. J Infect Dis 184:150–158 [View Article][PubMed]
    [Google Scholar]
  5. Aiastui A., Pucciarelli M. G., García-del Portillo F. ( 2010). Salmonella enterica serovar typhimurium invades fibroblasts by multiple routes differing from the entry into epithelial cells. Infect Immun 78:2700–2713 [View Article][PubMed]
    [Google Scholar]
  6. Arroyo A. G., Sánchez-Mateos P., Campanero M. R., Martín-Padura I., Dejana E., Sánchez-Madrid F. ( 1992). Regulation of the VLA integrin-ligand interactions through the β1 subunit. J Cell Biol 117:659–670 [View Article][PubMed]
    [Google Scholar]
  7. Arthur W. T., Petch L. A., Burridge K. ( 2000). Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. Curr Biol 10:719–722 [View Article][PubMed]
    [Google Scholar]
  8. Bandi V., Apicella M. A., Mason E., Murphy T. F., Siddiqi A., Atmar R. L., Greenberg S. B. ( 2001). Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis. Am J Respir Crit Care Med 164:2114–2119[PubMed] [CrossRef]
    [Google Scholar]
  9. Barnes P. J. ( 2006). Novel signal transduction modulators for the treatment of airway diseases. Pharmacol Ther 109:238–245 [View Article][PubMed]
    [Google Scholar]
  10. Boettcher J. P., Kirchner M., Churin Y., Kaushansky A., Pompaiah M., Thorn H., Brinkmann V., Macbeath G., Meyer T. F. ( 2010). Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements. PLoS Biol 8:e1000457 [View Article][PubMed]
    [Google Scholar]
  11. Bouchet V., Hood D. W., Li J., Brisson J. R., Randle G. A., Martin A., Li Z., Goldstein R., Schweda E. K. & other authors ( 2003). Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media. Proc Natl Acad Sci U S A 100:8898–8903 [View Article][PubMed]
    [Google Scholar]
  12. Bower J. M., Eto D. S., Mulvey M. A. ( 2005). Covert operations of uropathogenic Escherichia coli within the urinary tract. Traffic 6:18–31 [View Article][PubMed]
    [Google Scholar]
  13. Bunney T. D., Katan M. ( 2010). Phosphoinositide signalling in cancer: beyond PI3K and PTEN. Nat Rev Cancer 10:342–352 [View Article][PubMed]
    [Google Scholar]
  14. Burrows L., Clark K., Mould A. P., Humphries M. J. ( 1999). Fine mapping of inhibitory anti-α5 monoclonal antibody epitopes that differentially affect integrin-ligand binding. Biochem J 344:527–533 [View Article][PubMed]
    [Google Scholar]
  15. Byrd M. S., Pang B., Mishra M., Swords W. E., Wozniak D. J. ( 2010). The Pseudomonas aeruginosa exopolysaccharide Psl facilitates surface adherence and NF-κB activation in A549 cells. MBio 1:e00140–e10 [View Article][PubMed]
    [Google Scholar]
  16. Campanero M. R., Arroyo A. G., Pulido R., Ursa A., de Matías M. S., Sánchez-Mateos P., Kassner P. D., Chan B. M., Hemler M. E. & other authors ( 1992). Functional role of α2/β1 and α4/β1 integrins in leukocyte intercellular adhesion induced through the common β1 subunit. Eur J Immunol 22:3111–3119 [View Article][PubMed]
    [Google Scholar]
  17. Carabeo R. ( 2011). Bacterial subversion of host actin dynamics at the plasma membrane. Cell Microbiol 13:1460–1469 [View Article][PubMed]
    [Google Scholar]
  18. Caswell P. T., Vadrevu S., Norman J. C. ( 2009). Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol 10:843–853 [View Article][PubMed]
    [Google Scholar]
  19. Chakrabarti A. K., Vipat V. C., Mukherjee S., Singh R., Pawar S. D., Mishra A. C. ( 2010). Host gene expression profiling in influenza A virus-infected lung epithelial (A549) cells: a comparative analysis between highly pathogenic and modified H5N1 viruses. Virol J 7:219 [View Article][PubMed]
    [Google Scholar]
  20. Cho B. A., Cho N. H., Seong S. Y., Choi M. S., Kim I. S. ( 2010). Intracellular invasion by Orientia tsutsugamushi is mediated by integrin signaling and actin cytoskeleton rearrangements. Infect Immun 78:1915–1923 [View Article][PubMed]
    [Google Scholar]
  21. Clementi C., Murphy T. F. ( 2011). Non-typable Haemophilus influenzae invasion and persistence in the human respiratory tract. Front Cell Infect Microbiol 1:1–9 [View Article]
    [Google Scholar]
  22. Cossart P., Sansonetti P. J. ( 2004). Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304:242–248 [View Article][PubMed]
    [Google Scholar]
  23. del Pozo M. A., Alderson N. B., Kiosses W. B., Chiang H. H., Anderson R. G., Schwartz M. A. ( 2004). Integrins regulate Rac targeting by internalization of membrane domains. Science 303:839–842 [View Article][PubMed]
    [Google Scholar]
  24. Engelman J. A., Luo J., Cantley L. C. ( 2006). The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606–619 [View Article][PubMed]
    [Google Scholar]
  25. Fang K. M., Shu W. H., Chang H. C., Wang J. J., Mak O. T. ( 2004). Study of prostaglandin receptors in mitochondria on apoptosis of human lung carcinoma cell line A549. Biochem Soc Trans 32:1078–1080 [View Article][PubMed]
    [Google Scholar]
  26. Fink D. L., Green B. A., St Geme J. W. III ( 2002). The Haemophilus influenzae Hap autotransporter binds to fibronectin, laminin, and collagen IV. Infect Immun 70:4902–4907 [View Article][PubMed]
    [Google Scholar]
  27. Forsgren J., Samuelson A., Ahlin A., Jonasson J., Rynnel-Dagöö B., Lindberg A. ( 1994). Haemophilus influenzae resides and multiplies intracellularly in human adenoid tissue as demonstrated by in situ hybridization and bacterial viability assay. Infect Immun 62:673–679[PubMed]
    [Google Scholar]
  28. Foxwell A. R., Kyd J. M., Cripps A. W. ( 1998). Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol Mol Biol Rev 62:294–308[PubMed]
    [Google Scholar]
  29. Gilsdorf J. R., Marrs C. F., Foxman B. ( 2004). Haemophilus influenzae: genetic variability and natural selection to identify virulence factors. Infect Immun 72:2457–2461 [View Article][PubMed]
    [Google Scholar]
  30. Guarino M. ( 2010). Src signaling in cancer invasion. J Cell Physiol 223:14–26[PubMed]
    [Google Scholar]
  31. Guo L., Zhang F., Cai Y., Liu T. ( 2009). Expression profiling of integrins in lung cancer cells. Pathol Res Pract 205:847–853 [View Article][PubMed]
    [Google Scholar]
  32. Hallström T., Singh B., Resman F., Blom A. M., Mörgelin M., Riesbeck K. ( 2011). Haemophilus influenzae protein E binds to the extracellular matrix by concurrently interacting with laminin and vitronectin. J Infect Dis 204:1065–1074 [View Article][PubMed]
    [Google Scholar]
  33. Hammerschmidt S., Wolff S., Hocke A., Rosseau S., Müller E., Rohde M. ( 2005). Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun 73:4653–4667 [View Article][PubMed]
    [Google Scholar]
  34. Heasman S. J., Ridley A. J. ( 2008). Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9:690–701 [View Article][PubMed]
    [Google Scholar]
  35. Hill D. J., Toleman M. A., Evans D. J., Villullas S., Van Alphen L., Virji M. ( 2001). The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1. Mol Microbiol 39:850–862 [View Article][PubMed]
    [Google Scholar]
  36. Hoffmann C., Ohlsen K., Hauck C. R. ( 2011). Integrin-mediated uptake of fibronectin-binding bacteria. Eur J Cell Biol 90:891–896 [View Article][PubMed]
    [Google Scholar]
  37. Howe A. K. ( 2004). Regulation of actin-based cell migration by cAMP/PKA. Biochim Biophys Acta 1692:159–174 [View Article][PubMed]
    [Google Scholar]
  38. Huveneers S., Danen E. H. ( 2009). Adhesion signaling - crosstalk between integrins, Src and Rho. J Cell Sci 122:1059–1069 [View Article][PubMed]
    [Google Scholar]
  39. Ketterer M. R., Shao J. Q., Hornick D. B., Buscher B., Bandi V. K., Apicella M. A. ( 1999). Infection of primary human bronchial epithelial cells by Haemophilus influenzae: macropinocytosis as a mechanism of airway epithelial cell entry. Infect Immun 67:4161–4170[PubMed]
    [Google Scholar]
  40. Kim D., Chung J. ( 2002). Akt: versatile mediator of cell survival and beyond. J Biochem Mol Biol 35:106–115 [View Article][PubMed]
    [Google Scholar]
  41. Krendel M., Zenke F. T., Bokoch G. M. ( 2002). Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nat Cell Biol 4:294–301 [View Article][PubMed]
    [Google Scholar]
  42. Maqueda A., Moyano J. V., Gutiérrez-López M. D., Ovalle S., Rodríguez-Frade J. M., Cabañas C., Garcia-Pardo A. ( 2006). Activation pathways of α4β1 integrin leading to distinct T-cell cytoskeleton reorganization, Rac1 regulation and Pyk2 phosphorylation. J Cell Physiol 207:746–756 [View Article][PubMed]
    [Google Scholar]
  43. Marignani P. A., Carpenter C. L. ( 2001). Vav2 is required for cell spreading. J Cell Biol 154:177–186 [View Article][PubMed]
    [Google Scholar]
  44. Martí-Lliteras P., Regueiro V., Morey P., Hood D. W., Saus C., Sauleda J., Agustí A. G., Bengoechea J. A., Garmendia J. ( 2009). Nontypeable Haemophilus influenzae clearance by alveolar macrophages is impaired by exposure to cigarette smoke. Infect Immun 77:4232–4242 [View Article][PubMed]
    [Google Scholar]
  45. Martí-Lliteras P., López-Gómez A., Mauro S., Hood D. W., Viadas C., Calatayud L., Morey P., Servin A., Liñares J. & other authors ( 2011). Nontypable Haemophilus influenzae displays a prevalent surface structure molecular pattern in clinical isolates. PLoS ONE 6:e21133 [View Article][PubMed]
    [Google Scholar]
  46. Martin K. H., Slack J. K., Boerner S. A., Martin C. C., Parsons J. T. ( 2002). Integrin connections map: to infinity and beyond. Science 296:1652–1653 [View Article][PubMed]
    [Google Scholar]
  47. Mata M., Morcillo E., Gimeno C., Cortijo J. ( 2011). N-Acetyl-l-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV). Biochem Pharmacol 82:548–555 [View Article][PubMed]
    [Google Scholar]
  48. Mejía E., Bliska J. B., Viboud G. I. ( 2008). Yersinia controls type III effector delivery into host cells by modulating Rho activity. PLoS Pathog 4:e3 [View Article][PubMed]
    [Google Scholar]
  49. Mitra S. K., Hanson D. A., Schlaepfer D. D. ( 2005). Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6:56–68 [View Article][PubMed]
    [Google Scholar]
  50. Morey P., Cano V., Martí-Lliteras P., López-Gómez A., Regueiro V., Saus C., Bengoechea J. A., Garmendia J. ( 2011). Evidence for a non-replicative intracellular stage of nontypable Haemophilus influenzae in epithelial cells. Microbiology 157:234–250 [View Article][PubMed]
    [Google Scholar]
  51. Muenzner P., Bachmann V., Zimmermann W., Hentschel J., Hauck C. R. ( 2010). Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation. Science 329:1197–1201 [View Article][PubMed]
    [Google Scholar]
  52. Murphy T. F., Brauer A. L., Schiffmacher A. T., Sethi S. ( 2004). Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 170:266–272 [View Article][PubMed]
    [Google Scholar]
  53. Nagasawa S. Y., Takuwa N., Sugimoto N., Mabuchi H., Takuwa Y. ( 2005). Inhibition of Rac activation as a mechanism for negative regulation of actin cytoskeletal reorganization and cell motility by cAMP. Biochem J 385:737–744 [View Article][PubMed]
    [Google Scholar]
  54. O’Connor K. L., Mercurio A. M. ( 2001). Protein kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma cells. J Biol Chem 276:47895–47900[PubMed]
    [Google Scholar]
  55. Oviedo-Boyso J., Cortés-Vieyra R., Huante-Mendoza A., Yu H. B., Valdez-Alarcón J. J., Bravo-Patiño A., Cajero-Juárez M., Finlay B. B., Baizabal-Aguirre V. M. ( 2011). The phosphoinositide-3-kinase-Akt signaling pathway is important for Staphylococcus aureus internalization by endothelial cells. Infect Immun 79:4569–4577 [View Article][PubMed]
    [Google Scholar]
  56. Ozeri V., Rosenshine I., Ben-Ze’Ev A., Bokoch G. M., Jou T. S., Hanski E. ( 2001). De novo formation of focal complex-like structures in host cells by invading Streptococci. Mol Microbiol 41:561–573 [View Article][PubMed]
    [Google Scholar]
  57. Pizarro-Cerdá J., Cossart P. ( 2004). Subversion of phosphoinositide metabolism by intracellular bacterial pathogens. Nat Cell Biol 6:1026–1033 [View Article][PubMed]
    [Google Scholar]
  58. Raftopoulou M., Hall A. ( 2004). Cell migration: Rho GTPases lead the way. Dev Biol 265:23–32 [View Article][PubMed]
    [Google Scholar]
  59. Rao V. K., Krasan G. P., Hendrixson D. R., Dawid S., St Geme J. W. III ( 1999). Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae . FEMS Microbiol Rev 23:99–129[PubMed] [CrossRef]
    [Google Scholar]
  60. Regueiro V., Campos M. A., Morey P., Sauleda J., Agustí A. G., Garmendia J., Bengoechea J. A. ( 2009). Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers. Eur Respir J 33:273–281 [View Article][PubMed]
    [Google Scholar]
  61. Ridley A. J., Schwartz M. A., Burridge K., Firtel R. A., Ginsberg M. H., Borisy G., Parsons J. T., Horwitz A. R. ( 2003). Cell migration: integrating signals from front to back. Science 302:1704–1709 [View Article][PubMed]
    [Google Scholar]
  62. Sethi S., Murphy T. F. ( 2001). Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 14:336–363 [View Article][PubMed]
    [Google Scholar]
  63. Sethi S., Murphy T. F. ( 2008). Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 359:2355–2365 [View Article][PubMed]
    [Google Scholar]
  64. Sethi S., Evans N., Grant B. J., Murphy T. F. ( 2002). New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 347:465–471 [View Article][PubMed]
    [Google Scholar]
  65. Song J., Bishop B. L., Li G., Duncan M. J., Abraham S. N. ( 2007). TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder. Cell Host Microbe 1:287–298 [View Article][PubMed]
    [Google Scholar]
  66. St Geme J. W. III ( 2002). Molecular and cellular determinants of non-typeable Haemophilus influenzae adherence and invasion. Cell Microbiol 4:191–200 [View Article][PubMed]
    [Google Scholar]
  67. St Geme J. W. III, Falkow S. ( 1990). Haemophilus influenzae adheres to and enters cultured human epithelial cells. Infect Immun 58:4036–4044[PubMed]
    [Google Scholar]
  68. Swords W. E., Buscher B. A., Ver Steeg Ii K., Preston A., Nichols W. A., Weiser J. N., Gibson B. W., Apicella M. A. ( 2000). Non-typeable Haemophilus influenzae adhere to and invade human bronchial epithelial cells via an interaction of lipooligosaccharide with the PAF receptor. Mol Microbiol 37:13–27 [View Article][PubMed]
    [Google Scholar]
  69. Takesono A., Heasman S. J., Wojciak-Stothard B., Garg R., Ridley A. J. ( 2010). Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. PLoS ONE 5:e8774 [View Article][PubMed]
    [Google Scholar]
  70. Uliczka F., Kornprobst T., Eitel J., Schneider D., Dersch P. ( 2009). Cell invasion of Yersinia pseudotuberculosis by invasin and YadA requires protein kinase C, phospholipase C-γ1 and Akt kinase. Cell Microbiol 11:1782–1801 [View Article][PubMed]
    [Google Scholar]
  71. Van den Broeke C., Radu M., Chernoff J., Favoreel H. W. ( 2010). An emerging role for p21-activated kinases (Paks) in viral infections. Trends Cell Biol 20:160–169 [View Article][PubMed]
    [Google Scholar]
  72. Vancheri C., Mastruzzo C., Sortino M. A., Crimi N. ( 2004). The lung as a privileged site for the beneficial actions of PGE2. Trends Immunol 25:40–46 [View Article][PubMed]
    [Google Scholar]
  73. Virji M., Kayhty H., Ferguson D. J., Alexandrescu C., Moxon E. R. ( 1991). Interactions of Haemophilus influenzae with cultured human endothelial cells. Microb Pathog 10:231–245 [View Article][PubMed]
    [Google Scholar]
  74. Waschke J., Drenckhahn D., Adamson R. H., Barth H., Curry F. E. ( 2004). cAMP protects endothelial barrier functions by preventing Rac-1 inhibition. Am J Physiol Heart Circ Physiol 287:H2427–H2433 [View Article][PubMed]
    [Google Scholar]
  75. Watabe-Uchida M., John K. A., Janas J. A., Newey S. E., Van Aelst L. ( 2006). The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron 51:727–739 [View Article][PubMed]
    [Google Scholar]
  76. Weernink P. A., Meletiadis K., Hommeltenberg S., Hinz M., Ishihara H., Schmidt M., Jakobs K. H. ( 2004). Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42. J Biol Chem 279:7840–7849 [View Article][PubMed]
    [Google Scholar]
  77. Wittmann T., Bokoch G. M., Waterman-Storer C. M. ( 2004). Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1. J Biol Chem 279:6196–6203 [View Article][PubMed]
    [Google Scholar]
  78. Wong K. W., Isberg R. R. ( 2003). Arf6 and phosphoinositol-4-phosphate-5-kinase activities permit bypass of the Rac1 requirement for beta1 integrin-mediated bacterial uptake. J Exp Med 198:603–614 [View Article][PubMed]
    [Google Scholar]
  79. Xue Q., Jenkins S. A., Gu C., Smeds E., Liu Q., Vasan R., Russell B. H., Xu Y. ( 2010). Bacillus anthracis spore entry into epithelial cells is an actin-dependent process requiring c-Src and PI3K. PLoS ONE 5:e11665 [View Article][PubMed]
    [Google Scholar]
  80. Yamada M., Tamura Y., Sanzen N., Sato-Nishiuchi R., Hasegawa H., Ashman L. K., Rubinstein E., Yáñez-Mó M., Sánchez-Madrid F., Sekiguchi K. ( 2008). Probing the interaction of tetraspanin CD151 with integrin α3β1 using a panel of monoclonal antibodies with distinct reactivities toward the CD151-integrin α3β1 complex. Biochem J 415:417–427 [View Article][PubMed]
    [Google Scholar]
  81. Yoshida S., Sasakawa C. ( 2003). Exploiting host microtubule dynamics: a new aspect of bacterial invasion. Trends Microbiol 11:139–143 [View Article][PubMed]
    [Google Scholar]
  82. Zimmermann L., Peterhans E., Frey J. ( 2010). RGD motif of lipoprotein T, involved in adhesion of Mycoplasma conjunctivae to lamb synovial tissue cells. J Bacteriol 192:3773–3779 [View Article][PubMed]
    [Google Scholar]
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