1887

Abstract

Nontypable (NTHi) is a Gram-negative, non-capsulated human bacterial pathogen, a major cause of a repertoire of respiratory infections, and intimately associated with persistent lung bacterial colonization in patients suffering from chronic obstructive pulmonary disease (COPD). Despite its medical relevance, relatively little is known about its mechanisms of pathogenicity. In this study, we found that NTHi invades the airway epithelium by a distinct mechanism, requiring microtubule assembly, lipid rafts integrity, and activation of phosphatidylinositol 3-kinase (PI3K) signalling. We found that the majority of intracellular bacteria are located inside an acidic subcellular compartment, in a metabolically active and non-proliferative state. This NTHi-containing vacuole (NTHi-CV) is endowed with late endosome features, co-localizing with LysoTracker, lamp-1, lamp-2, CD63 and Rab7. The NTHi-CV does not acquire Golgi- or autophagy-related markers. These observations were extended to immortalized and primary human airway epithelial cells. By using NTHi clinical isolates expressing different amounts of phosphocholine (PCho), a major modification of NTHi lipooligosaccharide, on their surfaces, and an isogenic mutant strain lacking PCho, we showed that PCho is not responsible for NTHi intracellular location. In sum, this study indicates that NTHi can survive inside airway epithelial cells.

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2011-01-01
2019-10-16
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References

  1. 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.[CrossRef]
    [Google Scholar]
  2. Amann, R. I., Ludwig, W. & Schleifer, K. H. ( 1995; ). Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol Rev 59, 143–169.
    [Google Scholar]
  3. Amer, A. O. & Swanson, M. S. ( 2002; ). A phagosome of one's own: a microbial guide to life in the macrophage. Curr Opin Microbiol 5, 56–61.[CrossRef]
    [Google Scholar]
  4. 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.[CrossRef]
    [Google Scholar]
  5. Berón, W., Gutierrez, M. G., Rabinovitch, M. & Colombo, M. I. ( 2002; ). Coxiella burnetii localizes in a Rab7-labeled compartment with autophagic characteristics. Infect Immun 70, 5816–5821.[CrossRef]
    [Google Scholar]
  6. Bertaux, J., Schmid, M., Prevost-Boure, N. C., Churin, J. L., Hartmann, A., Garbaye, J. & Frey-Klett, P. ( 2003; ). In situ identification of intracellular bacteria related to Paenibacillus spp. in the mycelium of the ectomycorrhizal fungus Laccaria bicolor S238N. Appl Environ Microbiol 69, 4243–4248.[CrossRef]
    [Google Scholar]
  7. Binker, M. G., Cosen-Binker, L. I., Terebiznik, M. R., Mallo, G. V., McCaw, S. E., Eskelinen, E. L., Willenborg, M., Brumell, J. H., Saftig, P. & other authors ( 2007; ). Arrested maturation of Neisseria-containing phagosomes in the absence of the lysosome-associated membrane proteins, LAMP-1 and LAMP-2. Cell Microbiol 9, 2153–2166.[CrossRef]
    [Google Scholar]
  8. 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.[CrossRef]
    [Google Scholar]
  9. Cano, D. A., Martínez-Moya, M., Pucciarelli, M. G., Groisman, E. A., Casadesus, J. & García-del Portillo, F. ( 2001; ). Salmonella enterica serovar Typhimurium response involved in attenuation of pathogen intracellular proliferation. Infect Immun 69, 6463–6474.[CrossRef]
    [Google Scholar]
  10. Christensen, H., Hansen, M. & Sorensen, J. ( 1999; ). Counting and size classification of active soil bacteria by fluorescence in situ hybridization with an rRNA oligonucleotide probe. Appl Environ Microbiol 65, 1753–1761.
    [Google Scholar]
  11. Cosio, M., Ghezzo, H., Hogg, J. C., Corbin, R., Loveland, M., Dosman, J. & Macklem, P. T. ( 1978; ). The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med 298, 1277–1281.[CrossRef]
    [Google Scholar]
  12. Cosio, M. G., Saetta, M. & Agusti, A. ( 2009; ). Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med 360, 2445–2454.[CrossRef]
    [Google Scholar]
  13. Cossart, P. & Sansonetti, P. J. ( 2004; ). Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304, 242–248.[CrossRef]
    [Google Scholar]
  14. Erwin, A. L. & Smith, A. L. ( 2007; ). Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior. Trends Microbiol 15, 355–362.[CrossRef]
    [Google Scholar]
  15. Eswarappa, S. M. ( 2009; ). Location of pathogenic bacteria during persistent infections: insights from an analysis using game theory. PLoS ONE 4, e5383.[CrossRef]
    [Google Scholar]
  16. Fink, D. L., Buscher, A. Z., Green, B., Fernsten, P. & St Geme, J. W., III ( 2003; ). The Haemophilus influenzae Hap autotransporter mediates microcolony formation and adherence to epithelial cells and extracellular matrix via binding regions in the C-terminal end of the passenger domain. Cell Microbiol 5, 175–186.[CrossRef]
    [Google Scholar]
  17. Forsgren, J., Samuelson, A., Ahlin, A., Jonasson, J., Rynnel-Dagoo, 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.
    [Google Scholar]
  18. Foxwell, A. R., Kyd, J. M. & Cripps, A. W. ( 1998; ). Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol Mol Biol Rev 62, 294–308.
    [Google Scholar]
  19. Galán, J. E., Ginocchio, C. & Costeas, P. ( 1992; ). Molecular and functional characterization of the Salmonella invasion gene invA – homology of InvA to members of a new protein family. J Bacteriol 174, 4338–4349.
    [Google Scholar]
  20. García-del Portillo, F. & Finlay, B. B. ( 1994; ). Salmonella invasion of nonphagocytic cells induces formation of macropinosomes in the host cell. Infect Immun 62, 4641–4645.
    [Google Scholar]
  21. García-del Portillo, F., Núñez-Hernández, C., Eisman, B. & Ramos-Vivas, J. ( 2008; ). Growth control in the Salmonella-containing vacuole. Curr Opin Microbiol 11, 46–52.[CrossRef]
    [Google Scholar]
  22. Garin, J., Díez, R., Kieffer, S., Dermine, J. F., Duclos, S., Gagnon, E., Sadoul, R., Rondeau, C. & Desjardins, M. ( 2001; ). The phagosome proteome: insight into phagosome functions. J Cell Biol 152, 165–180.[CrossRef]
    [Google Scholar]
  23. Garvis, S., Beuzón, C. & Holden, D. W. ( 2001; ). A role for the PhoP/Q regulon in inhibition of fusion between lysosomes and Salmonella-containing vacuoles in macrophages. Cell Microbiol 3, 731–744.[CrossRef]
    [Google Scholar]
  24. 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.[CrossRef]
    [Google Scholar]
  25. Guignot, J., Hudault, S., Kansau, I., Chau, I. & Servin, A. L. ( 2009; ). Human decay-accelerating factor and CEACAM receptor-mediated internalization and intracellular lifestyle of Afa/Dr diffusely adhering Escherichia coli in epithelial cells. Infect Immun 77, 517–531.[CrossRef]
    [Google Scholar]
  26. Haas, A. ( 2007; ). The phagosome: compartment with a license to kill. Traffic 8, 311–330.[CrossRef]
    [Google Scholar]
  27. Harrison, A., Dyer, D. W., Gillaspy, A., Ray, W. C., Mungur, R., Carson, M. B., Zhong, H., Gipson, J., Gipson, M. & other authors ( 2005; ). Genomic sequence of an otitis media isolate of nontypeable Haemophilus influenzae: comparative study with H. influenzae serotype d, strain KW20. J Bacteriol 187, 4627–4636.[CrossRef]
    [Google Scholar]
  28. Hendrixson, D. R. & St Geme, J. W., III ( 1998; ). The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein. Mol Cell 2, 841–850.[CrossRef]
    [Google Scholar]
  29. Holmes, K. A. & Bakaletz, L. O. ( 1997; ). Adherence of non-typeable Haemophilus influenzae promotes reorganization of the actin cytoskeleton in human or chinchilla epithelial cells in vitro. Microb Pathog 23, 157–166.[CrossRef]
    [Google Scholar]
  30. Hong, W., Mason, K., Jurcisek, J., Novotny, L., Bakaletz, L. O. & Swords, W. E. ( 2007a; ). Phosphorylcholine decreases early inflammation and promotes the establishment of stable biofilm communities of nontypeable Haemophilus influenzae strain 86-028NP in a chinchilla model of otitis media. Infect Immun 75, 958–965.[CrossRef]
    [Google Scholar]
  31. Hong, W., Pang, B., West-Barnette, S. & Swords, W. E. ( 2007b; ). Phosphorylcholine expression by nontypeable Haemophilus influenzae correlates with maturation of biofilm communities in vitro and in vivo. J Bacteriol 189, 8300–8307.[CrossRef]
    [Google Scholar]
  32. Isberg, R. R., Voorhis, D. L. & Falkow, S. ( 1987; ). Identification of invasin: a protein that allows enteric bacteria to penetrate cultured mammalian cells. Cell 50, 769–778.[CrossRef]
    [Google Scholar]
  33. Ji, W. T. & Liu, H. J. ( 2008; ). PI3K-Akt signaling and viral infection. Recent Pat Biotechnol 2, 218–226.[CrossRef]
    [Google Scholar]
  34. Kadioglu, A., Weiser, J. N., Paton, J. C. & Andrew, P. W. ( 2008; ). The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol 6, 288–301.[CrossRef]
    [Google Scholar]
  35. Kaufmann, S. H. & Schaible, U. E. ( 2005; ). Antigen presentation and recognition in bacterial infections. Curr Opin Immunol 17, 79–87.[CrossRef]
    [Google Scholar]
  36. Kenjale, R., Meng, G., Fink, D. L., Juehne, T., Ohashi, T., Erickson, H. P., Waksman, G. & St Geme, J. W., III ( 2009; ). Structural determinants of autoproteolysis of the Haemophilus influenzae Hap autotransporter. Infect Immun 77, 4704–4713.[CrossRef]
    [Google Scholar]
  37. 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.
    [Google Scholar]
  38. Kornfeld, S. ( 1986; ). Trafficking of lysosomal enzymes in normal and disease states. J Clin Invest 77, 1–6.[CrossRef]
    [Google Scholar]
  39. Kruskal, B. A., Sastry, K., Warner, A. B., Mathieu, C. E. & Ezekowitz, R. A. ( 1992; ). Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor. J Exp Med 176, 1673–1680.[CrossRef]
    [Google Scholar]
  40. Kumar, Y. & Valdivia, R. H. ( 2009; ). Leading a sheltered life: intracellular pathogens and maintenance of vacuolar compartments. Cell Host Microbe 5, 593–601.[CrossRef]
    [Google Scholar]
  41. Lambotin, M., Hoffmann, I., Laran-Chich, M. P., Nassif, X., Couraud, P. O. & Bourdoulous, S. ( 2005; ). Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide. J Cell Sci 118, 3805–3816.[CrossRef]
    [Google Scholar]
  42. Lamothe, J., Thyssen, S. & Valvano, M. A. ( 2004; ). Burkholderia cepacia complex isolates survive intracellularly without replication within acidic vacuoles of Acanthamoeba polyphaga. Cell Microbiol 6, 1127–1138.[CrossRef]
    [Google Scholar]
  43. Lamothe, J., Huynh, K. K., Grinstein, S. & Valvano, M. A. ( 2007; ). Intracellular survival of Burkholderia cenocepacia in macrophages is associated with a delay in the maturation of bacteria-containing vacuoles. Cell Microbiol 9, 40–53.[CrossRef]
    [Google Scholar]
  44. Ludwig, T., Munier-Lehmann, H., Bauer, U., Hollinshead, M., Ovitt, C., Lobel, P. & Hoflack, B. ( 1994; ). Differential sorting of lysosomal enzymes in mannose 6-phosphate receptor-deficient fibroblasts. EMBO J 13, 3430–3437.
    [Google Scholar]
  45. Luzio, J. P., Pryor, P. R. & Bright, N. A. ( 2007; ). Lysosomes: fusion and function. Nat Rev Mol Cell Biol 8, 622–632.[CrossRef]
    [Google Scholar]
  46. Lysenko, E. S., Gould, J., Bals, R., Wilson, J. M. & Weiser, J. N. ( 2000; ). Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect Immun 68, 1664–1671.[CrossRef]
    [Google Scholar]
  47. Mañes, S., del Real, G. & Martínez, A. ( 2003; ). Pathogens: raft hijackers. Nat Rev Immunol 3, 557–568.[CrossRef]
    [Google Scholar]
  48. Manz, W., Szewzyk, U., Ericsson, P., Amann, R., Schleifer, K. H. & Stenstrom, T. A. ( 1993; ). In situ identification of bacteria in drinking water and adjoining biofilms by hybridization with 16S-rRNA-directed and 23S-rRNA-directed fluorescent oligonucleotide probes. Appl Environ Microbiol 59, 2293–2298.
    [Google Scholar]
  49. Martí-Lliteras, P., Regueiro, V., Morey, P., Hood, D. W., Saus, C., Sauleda, J., Agustí, A. G., Bengoechea, J. A. & Garmendia, J. ( 2009; ). Non-typable Haemophilus influenzae clearance by alveolar macrophages is impaired by exposure to cigarette smoke. Infect Immun 77, 4232–4242.[CrossRef]
    [Google Scholar]
  50. Martínez de Tejada, G. & Moriyón, I. ( 1993; ). The outer membranes of Brucella spp. are not barriers to hydrophobic permeants. J Bacteriol 175, 5273–5275.
    [Google Scholar]
  51. Martínez-Moya, M., de Pedro, M. A., Schwarz, H. & García-del Portillo, F. ( 1998; ). Inhibition of Salmonella intracellular proliferation by non-phagocytic eucaryotic cells. Res Microbiol 149, 309–318.[CrossRef]
    [Google Scholar]
  52. Monack, D. M., Mueller, A. & Falkow, S. ( 2004; ). Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat Rev Microbiol 2, 747–765.[CrossRef]
    [Google Scholar]
  53. Moxon, E. R., Sweetman, W. A., Deadman, M. E., Ferguson, D. J. & Hood, D. W. ( 2008; ). Haemophilus influenzae biofilms: hypothesis or fact? Trends Microbiol 16, 95–100.[CrossRef]
    [Google Scholar]
  54. Munier-Lehmann, H., Mauxion, F., Bauer, U., Lobel, P. & Hoflack, B. ( 1996; ). Re-expression of the mannose 6-phosphate receptors in receptor-deficient fibroblasts. Complementary function of the two mannose 6-phosphate receptors in lysosomal enzyme targeting. J Biol Chem 271, 15166–15174.[CrossRef]
    [Google Scholar]
  55. Murphy, T. F. & Kirkham, C. ( 2002; ). Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili. BMC Microbiol 2, 7.[CrossRef]
    [Google Scholar]
  56. Mysorekar, I. U. & Hultgren, S. J. ( 2006; ). Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci U S A 103, 14170–14175.[CrossRef]
    [Google Scholar]
  57. Neef, A., Zaglauer, A., Meier, H., Amann, R., Lemmer, H. & Schleifer, K. H. ( 1996; ). Population analysis in a denitrifying sand filter: conventional and in situ identification of Paracoccus spp. in methanol-fed biofilms. Appl Environ Microbiol 62, 4329–4339.
    [Google Scholar]
  58. Oelschlaeger, T. A., Guerry, P. & Kopecko, D. J. ( 1993; ). Unusual microtubule-dependent endocytosis mechanisms triggered by Campylobacter jejuni and Citrobacter freundii. Proc Natl Acad Sci U S A 90, 6884–6888.[CrossRef]
    [Google Scholar]
  59. Orvedahl, A. & Levine, B. ( 2009; ). Eating the enemy within: autophagy in infectious diseases. Cell Death Differ 16, 57–69.[CrossRef]
    [Google Scholar]
  60. Pang, B., Winn, D., Johnson, R., Hong, W., West-Barnette, S., Kock, N. & Swords, W. E. ( 2008; ). Lipooligosaccharides containing phosphorylcholine delay pulmonary clearance of nontypeable Haemophilus influenzae. Infect Immun 76, 2037–2043.[CrossRef]
    [Google Scholar]
  61. Perez Vidakovics, M. L. & Riesbeck, K. ( 2009; ). Virulence mechanisms of Moraxella in the pathogenesis of infection. Curr Opin Infect Dis 22, 279–285.[CrossRef]
    [Google Scholar]
  62. Pizarro-Cerdá, J. & Cossart, P. ( 2004; ). Subversion of phosphoinositide metabolism by intracellular bacterial pathogens. Nat Cell Biol 6, 1026–1033.[CrossRef]
    [Google Scholar]
  63. Power, P. M., Sweetman, W. A., Gallacher, N. J., Woodhall, M. R., Kumar, G. A., Moxon, E. R. & Hood, D. W. ( 2009; ). Simple sequence repeats in Haemophilus influenzae. Infect Genet Evol 9, 216–228.[CrossRef]
    [Google Scholar]
  64. 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.[CrossRef]
    [Google Scholar]
  65. Ray, K., Marteyn, B., Sansonetti, P. J. & Tang, C. M. ( 2009; ). Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nat Rev Microbiol 7, 333–340.[CrossRef]
    [Google Scholar]
  66. Regueiro, V., Campos, M. A., Morey, P., Sauleda, J., Agusti, 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.
    [Google Scholar]
  67. Rennard, S. I. & Vestbo, J. ( 2006; ). COPD: the dangerous underestimate of 15 %. Lancet 367, 1216–1219.[CrossRef]
    [Google Scholar]
  68. Rosenberger, C. M., Brumell, J. H. & Finlay, B. B. ( 2000; ). Microbial pathogenesis: lipid rafts as pathogen portals. Curr Biol 10, R823–R825.[CrossRef]
    [Google Scholar]
  69. Salcedo, S. P. & Holden, D. W. ( 2005; ). Bacterial interactions with the eukaryotic secretory pathway. Curr Opin Microbiol 8, 92–98.[CrossRef]
    [Google Scholar]
  70. Schülein, R., Seubert, A., Gille, C., Lanz, C., Hansmann, Y., Piemont, Y. & Dehio, C. ( 2001; ). Invasion and persistent intracellular colonization of erythrocytes. A unique parasitic strategy of the emerging pathogen Bartonella. J Exp Med 193, 1077–1086.[CrossRef]
    [Google Scholar]
  71. Schweda, E. K., Richards, J. C., Hood, D. W. & Moxon, E. R. ( 2007; ). Expression and structural diversity of the lipopolysaccharide of Haemophilus influenzae: implication in virulence. Int J Med Microbiol 297, 297–306.[CrossRef]
    [Google Scholar]
  72. Sethi, S. ( 2000; ). Bacterial infection and the pathogenesis of COPD. Chest 117, 286S–291S.[CrossRef]
    [Google Scholar]
  73. 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.[CrossRef]
    [Google Scholar]
  74. Sethi, S. & Murphy, T. F. ( 2008; ). Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 359, 2355–2365.[CrossRef]
    [Google Scholar]
  75. 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.[CrossRef]
    [Google Scholar]
  76. St Geme, J. W., III ( 2002; ). Molecular and cellular determinants of non-typeable Haemophilus influenzae adherence and invasion. Cell Microbiol 4, 191–200.[CrossRef]
    [Google Scholar]
  77. St Geme, J. W., III & Falkow, S. ( 1990; ). Haemophilus influenzae adheres to and enters cultured human epithelial cells. Infect Immun 58, 4036–4044.
    [Google Scholar]
  78. Swanson, J. ( 1989; ). Fluorescent labeling of endocytic compartments. Methods Cell Biol 29, 137–151.
    [Google Scholar]
  79. Swords, W. E., Buscher, B. A., Ver, S. I., 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.[CrossRef]
    [Google Scholar]
  80. Swords, W. E., Ketterer, M. R., Shao, J., Campbell, C. A., Weiser, J. N. & Apicella, M. A. ( 2001; ). Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling. Cell Microbiol 3, 525–536.[CrossRef]
    [Google Scholar]
  81. Veiga, E. & Cossart, P. ( 2006; ). The role of clathrin-dependent endocytosis in bacterial internalization. Trends Cell Biol 16, 499–504.[CrossRef]
    [Google Scholar]
  82. Virji, M. ( 2009; ). Pathogenic neisseriae: surface modulation, pathogenesis and infection control. Nat Rev Microbiol 7, 274–286.[CrossRef]
    [Google Scholar]
  83. 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.[CrossRef]
    [Google Scholar]
  84. Watson, R. O. & Galán, J. E. ( 2008; ). Campylobacter jejuni survives within epithelial cells by avoiding delivery to lysosomes. PLoS Pathog 4, e14.[CrossRef]
    [Google Scholar]
  85. Weiser, J. N., Pan, N., McGowan, K. L., Musher, D., Martin, A. & Richards, J. ( 1998; ). Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 187, 631–640.[CrossRef]
    [Google Scholar]
  86. West-Barnette, S., Rockel, A. & Swords, W. E. ( 2006; ). Biofilm growth increases phosphorylcholine content and decreases potency of nontypeable Haemophilus influenzae endotoxins. Infect Immun 74, 1828–1836.[CrossRef]
    [Google Scholar]
  87. Wright, K. J., Seed, P. C. & Hultgren, S. J. ( 2007; ). Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol 9, 2230–2241.[CrossRef]
    [Google Scholar]
  88. Yoshida, S. & Sasakawa, C. ( 2003; ). Exploiting host microtubule dynamics: a new aspect of bacterial invasion. Trends Microbiol 11, 139–143.[CrossRef]
    [Google Scholar]
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