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Pseudomonas aeruginosa pili and flagella mediate distinct binding and signaling events at the apical and basolateral surface of airway epithelium.
Open accessAbstract
Pseudomonas aeruginosa, an important opportunistic pathogen of man, exploits numerous factors for initial attachment to the host, an event required to establish bacterial infection. In this paper, we rigorously explore the role of two major bacterial adhesins, type IV pili (Tfp) and flagella, in bacterial adherence to distinct host receptors at the apical (AP) and basolateral (BL) surfaces of polarized lung epithelial cells and induction of subsequent host signaling and pathogenic events. Using an isogenic mutant of P. aeruginosa that lacks flagella or utilizing beads coated with purified Tfp, we establish that Tfp are necessary and sufficient for maximal binding to host N-glycans at the AP surface of polarized epithelium. In contrast, experiments utilizing a P. aeruginosa isogenic mutant that lacks Tfp or using beads coated with purified flagella demonstrate that flagella are necessary and sufficient for maximal binding to heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs) at the BL surface of polarized epithelium. Using two different cell-free systems, we demonstrate that Tfp-coated beads show highest binding affinity to complex N-glycan chains coated onto plastic plates and preferentially aggregate with beads coated with N-glycans, but not with single sugars or HS. In contrast, flagella-coated beads bind to or aggregate preferentially with HS or HSPGs, but demonstrate little binding to N-glycans. We further show that Tfp-mediated binding to host N-glycans results in activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and bacterial entry at the AP surface. At the BL surface, flagella-mediated binding to HS activates the epidermal growth factor receptor (EGFR), adaptor protein Shc, and PI3K/Akt, and induces bacterial entry. Remarkably, flagella-coated beads alone can activate EGFR and Shc. Together, this work provides new insights into the intricate interactions between P. aeruginosa and lung epithelium that may be potentially useful in the development of novel treatments for P. aeruginosa infections.
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“For example the exposure of apical receptors like integrins permit the adhesion of bacteria such as S. aureus and P. aeruginosa (Sanford et al., 1978; Davison and Sanford, 1981; Bucior et al., 2012; Smith and McCullers, 2014).”
From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Bucior et al., 2012
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Citations
Cites
Principles and Practice of Infectious Diseases.
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-9-818_5 · Cited by 12,045
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
Castagnola, E., Viscoli, C., & Mikulska, M. (2015) · Elsevier eBooks · doi:10.1016/c2012-1-00075-6 · Cited by 2,587
Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients
Smith, E. E., Buckley, D. G., Wu, Z., Saenphimmachak, C., Hoffman, L. R., D’Argenio, D. A., Miller, S. I., Ramsey, B. W., Speert, D. P., Moskowitz, S. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602138103 · Cited by 1,319
Type IV Pili and Twitching Motility
Mattick, J. S. (2002) · Annual Review of Microbiology · doi:10.1146/annurev.micro.56.012302.160938 · Cited by 1,257
Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
Kofoed, E. M., & Vance, R. E. (2011) · Nature · doi:10.1038/nature10394 · Cited by 894
Lightfield, K. L., Persson, J., Brubaker, S. W., Witte, C. E., von Moltke, J., Dunipace, E. A., Henry, T., Sun, Y., Cado, D., Dietrich, W. F., et al. (2008) · Nature Immunology · doi:10.1038/ni.1646 · Cited by 502
Role of Flagella in Pathogenesis ofPseudomonas aeruginosaPulmonary Infection
Feldman, M. F., Bryan, R. A., Rajan, S., Scheffler, L., Brunnert, S. R., Tang, H. B., & Prince, A. S. (1998) · Infection and Immunity · doi:10.1128/iai.66.1.43-51.1998 · Cited by 489
Dasgupta, N., Wolfgang, M. C., Goodman, A. L., Arora, S. K., Jyot, J., Lory, S. J., & Ramphal, R. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03740.x · Cited by 451
Vallet-Gély, I., Olson, J. W., Lory, S. J., Lazdunski, A. M., & Filloux, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111551898 · Cited by 355
Saiman, L. M., & Prince, A. S. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116779 · Cited by 347
Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria
Feuillet, V., Medjane, S., Mondor, I., Demaria, O., Pagni, P. P., Galán, J. E., Flavell, R. A., & Alexopoulou, L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605200103 · Cited by 337
Role of Pseudomonas aeruginosa type III effectors in disease
Engel, J. N., & Balachandran, P. (2009) · Current Opinion in Microbiology · doi:10.1016/j.mib.2008.12.007 · Cited by 330
Chemani, C., Imberty, A., de Bentzmann, S., Pierre, M., Wimmerová, M., Guery, B. P., & Faure, K. (2009) · Infection and Immunity · doi:10.1128/iai.01204-08 · Cited by 329
Toll-Like Receptors in Normal and Cystic Fibrosis Airway Epithelial Cells
Muir, A. B., Soong, G., Sokol, S., Reddy, B. D., Gómez, M. I., van Heeckeren, A. M., & Prince, A. S. (2003) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0329oc · Cited by 258
Koff, J. L., Shao, M. X. G., Ueki, I. F., & Nadel, J. A. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00025.2008 · Cited by 232
Liu, P. V. (1966) · The Journal of Infectious Diseases · doi:10.1093/infdis/116.4.481 · Cited by 226
Type IV pili of pathogenic Neisseriae elicit cortical plaque formation in epithelial cells
Merz, A. J., Enns, C. A., & So, M. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01459.x · Cited by 210
Keates, S. E., Sougioultzis, S., Keates, A. C., Zhao, D., Peek, R. M., Shaw, L. M., & Kelly, C. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107630200 · Cited by 194
Interaction of Pseudomonas aeruginosa with A549 pneumocyte cells
Chi, E. Y., Mehl, T., Nunn, D., & Lory, S. J. (1991) · Infection and Immunity · doi:10.1128/iai.59.3.822-828.1991 · Cited by 179
Epithelial cell polarity affects susceptibility to Pseudomonas aeruginosa invasion and cytotoxicity
Fleiszig, S. M. J., Evans, D. J., Do, N., Vallas, V., Shin, S., & Mostov, K. E. (1997) · Infection and Immunity · doi:10.1128/iai.65.7.2861-2867.1997 · Cited by 168
Bertrand, J. J., West, J. T., & Engel, J. N. (2009) · Journal of Bacteriology · doi:10.1128/jb.01390-09 · Cited by 148
A genomic island in Pseudomonas aeruginosa carries the determinants of flagellin glycosylation
Arora, S. K., Bangera, M. G., Lory, S. J., & Ramphal, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161249198 · Cited by 148
Bucior, I., Simon Scheuring, A., Engel, A. H., & Burger, M. M. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200309005 · Cited by 146
Pier, G. B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.8822 · Cited by 145
Comolli, J. C., Waite, L. L., Mostov, K. E., & Engel, J. N. (1999) · Infection and Immunity · doi:10.1128/iai.67.7.3207-3214.1999 · Cited by 134
Kierbel, A., Gassama‐Diagne, A., Mostov, K. E., & Engel, J. N. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-08-0717 · Cited by 131
Gotoh, N., Tojo, A., Muroya, K., Hashimoto, Y., Hattori, S., Nakamura, S., Takenawa, T., Yazaki, Y., & Shibuya, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.1.167 · Cited by 123
Identification of Pseudomonas aeruginosa genes required for epithelial cell injury
Kang, P. J., Hauser, A. R., Apodaca, G., Fleiszig, S. M. J., Wiener-Kronish, J. P., Mostov, K. E., & Engel, J. N. (1997) · Molecular Microbiology · doi:10.1046/j.1365-2958.1997.4311793.x · Cited by 121
Nagy, T. A., Frey, M. R., Yan, F., Israel, D. A., Polk, D. B., & Peek, R. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/596660 · Cited by 120
Yan, F., Cao, H., Chaturvedi, R., Krishna, U. S., Hobbs, S. S., Dempsey, P. J., Peek, R. M., Cover, T. L., Washington, M. K., Wilson, K. T., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2008.12.059 · Cited by 111
Koff, J. L., Shao, M. X. G., Kim, S., Ueki, I. F., & Nadel, J. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8693 · Cited by 111
Evans, D. J., Frank, D. W., Finck‐Barbançon, V., Wu, C. C., & Fleiszig, S. M. J. (1998) · Infection and Immunity · doi:10.1128/iai.66.4.1453-1459.1998 · Cited by 103
Scharfman, A., Arora, S. K., Delmotte, P. F., Brussel, E. V., Mazurier, J., Ramphal, R., & Roussel, P. (2001) · Infection and Immunity · doi:10.1128/iai.69.9.5243-5248.2001 · Cited by 101
Almagro, P., Salvadó, M., García‐Vidal, C., Rodríguez‐Carballeira, M., Cuchí, E., de-Torres, J. P., & Heredia, J. L. (2011) · Respiration · doi:10.1159/000331224 · Cited by 94
Roger, P., Puchelle, É., Bajolet-Laudinat, O., Tournier, J.-M., Debordeaux, C., Plotkowski, M.-C., Cohen, J. H. M., Sheppard, D., & de Bentzmann, S. (1999) · European Respiratory Journal · doi:10.1034/j.1399-3003.1999.13f14.x · Cited by 92
Seo, B., Choy, E. W., Maudsley, S. R., Miller, W. E., Wilson, B. A., & Luttrell, L. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.3.2239 · Cited by 87
Li, H., Schmid‐Bindert, G., Wang, D., Zhao, Y. F., Yang, X., Su, B., & Zhou, C. (2011) · Advances in Medical Sciences · doi:10.2478/v10039-011-0043-x · Cited by 85
The Role of Flagellin versus Motility in Acute Lung Disease Caused byPseudomonas aeruginosa
Balloy, V., Verma, A., Kuravi, S., Si‐Tahar, M., Chignard, M., & Ramphal, R. (2007) · The Journal of Infectious Diseases · doi:10.1086/518610 · Cited by 84
Esen, M., Grassmé, H., Riethmüller, J., Riehle, A., Fassbender, K. C., & Gulbins, E. (2001) · Infection and Immunity · doi:10.1128/iai.69.1.281-287.2001 · Cited by 81
Hybiske, K., Ichikawa, J. K., Huang, V., Lory, S., & Machen, T. E. (2003) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00342.x · Cited by 79
Bucior, I., Mostov, K. E., & Engel, J. N. (2009) · Infection and Immunity · doi:10.1128/iai.01215-09 · Cited by 79
Pielage, J. F., Powell, K. R., Kalman, D., & Engel, J. N. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000031 · Cited by 76
Franzetti, F., Grassini, A., Piazza, M., Degl’Innocenti, M., Bandera, A., Gazzola, L., Marchetti, G. C., & Gori, A. (2006) · Infection · doi:10.1007/s15010-006-5007-x · Cited by 65
Rush, J. S., Panneerselvam, K., Waechter, C. J., & Freeze, H. H. (2000) · Glycobiology · doi:10.1093/glycob/10.8.829 · Cited by 63
Molecular Pathogenesis of Acute Pseudomonas Aeruginosa Infections
Engel, J. N. (2003) · Perspectives on critical care infectious diseases · doi:10.1007/978-1-4615-0433-7_13 · Cited by 60
Wong, W. Y., McInnes, C., Sykes, B. D., PARANCHYCH, W., Irvin, R. T., & Hodges, R. S. (1995) · Biochemistry · doi:10.1021/bi00040a006 · Cited by 56
Mikami, F., He, G., Jono, H., Andalibi, A., Kai, H., & Li, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503941200 · Cited by 56
Lack of Adherence of Clinical Isolates of Pseudomonas aeruginosa to Asialo-GM 1 on Epithelial Cells
Schroeder, T. H., Zaidi, T., & Pier, G. B. (2001) · Infection and Immunity · doi:10.1128/iai.69.2.719-729.2001 · Cited by 56
Tseng, J., Jiun, L., Widdicombe, J. H., & Machen, T. E. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00166.2005 · Cited by 55
Toll-like receptor 5 forms asymmetric dimers in the absence of flagellin
Zhou, K., Kanai, R., Lee, P., Wang, H., & Modis, Y. (2011) · Journal of Structural Biology · doi:10.1016/j.jsb.2011.12.002 · Cited by 54
Zhang, J., Li, H., Wang, J., Dong, Z., Mian, S. I., & Yu, F. X. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-1323 · Cited by 54
Tramper‐Stranders, G. A., van der Ent, C. K., Molin, S., Yang, L., Hansen, S. K., Rau, M. H., Ciofu, O., Johansen, H. K., & Wolfs, T. F. W. (2011) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2011.03627.x · Cited by 47
Epithelial Cell Polarity Alters Rho-GTPase Responses toPseudomonas aeruginosa
Kazmierczak, B. I., Mostov, K. E., & Engel, J. N. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-08-0559 · Cited by 45
Lepanto, P., Bryant, D. M., Rossello, J., Datta, A., Mostov, K. E., & Kierbel, A. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01611.x · Cited by 42
Gao, N., Kumar, A., Jyot, J., & Yu, F.-S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009351 · Cited by 40
Neisseria gonorrhoeae-induced transactivation of EGFR enhances gonococcal invasion
Swanson, K. V., Griffiss, J. M., Edwards, V. L., Stein, D. C., & Song, W. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01603.x · Cited by 38
Bacterial Penetration of the Mucosal Barrier by Targeting Lipid Rafts
Abraham, S. N., Duncan, M. J., Li, G., & Zaas, D. (2005) · Journal of Investigative Medicine · doi:10.2310/6650.2005.53609 · Cited by 29
Evans, D. J., Kuo, T. C., Kwong, M. S. F., Van, R., & Fleiszig, S. M. J. (2002) · Microbial Pathogenesis · doi:10.1006/mpat.2002.0521 · Cited by 28
Gerçeker, A. A., Zaidi, T., Marks, P. W., Golan, D. E., & Pier, G. B. (2000) · Infection and Immunity · doi:10.1128/iai.68.2.861-870.2000 · Cited by 24
Emam, A., Yu, A., Park, H.-J., Mahfoud, R., Kus, J. V., Burrows, L. L., & Lingwood, C. A. (2006) · Microbiology · doi:10.1099/mic.0.28863-0 · Cited by 23
Bacterial pneumonia in the AIDS patients
Salami, A., Oluboyo, P., Akambi, A., & Fawibe, A. E. (2007) · West African Journal of Medicine · doi:10.4314/wajm.v25i1.28236 · Cited by 18
Song, J. S., Hyun, S. W., Lillihoj, E., & Kim, B. T. (2001) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2001.16.3.167 · Cited by 14
Superinfections in Pseudomonas aeruginosa ventilator-associated pneumonia.
Giantsou, E., & Manolas, K. I. (2011) · PubMed · Cited by 8
Pseudomonas aeruginosa Internalization by Non-Phagocytic Cells
Engel, J. N. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6097-7_12 · Cited by 7
Keates, S. E., Keates, A. C., Sougioultzis, S., Peek, R. M., & Kelly, C. P. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)80213-5 · Cited by 1
HIV/AIDS Case Histories: Diagnostic Problems
Godwin, T. A. (1998) · AIDS Patient Care and STDs · doi:10.1089/apc.1998.12.573 · Cited by 1
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The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update
Reynolds, D., & Kollef, M. H. (2021) · Drugs · doi:10.1007/s40265-021-01635-6 · Cited by 804
“aeruginosa infection, the main adhesins are the single flagellum, which is necessary for motility, adhesion to cells and formation of a biofilm, and the type IV pili, which are appendages composed of pilin polymers, which allow the bacteria to move over surfaces in addition to serving relevant roles in biofilm formati…”
BackgroundPseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors
Jurado‐Martín, I., Sainz-Mejías, M., & McClean, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063128 · Cited by 774
“Aside from motility, FliC protein is responsible for binding to (i) the membrane glycolipid asialo-GM1 on the apical surface of the lung epithelial cells [79], (ii) heparan sulphate proteoglycans localised on the basolateral surface [84], and (iii) SP-A surfactant [85], whereas FliD mediates adhesion to human”
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Haiko, J., & Westerlund-Wikström, B. (2013) · Biology · doi:10.3390/biology2041242 · Cited by 589
“Flagellum Adhesion Calu-3 basolateral surface HSPGs (b) [39]”
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“For example the exposure of apical receptors like integrins permit the adhesion of bacteria such as S. aureus and P. aeruginosa (Sanford et al., 1978; Davison and Sanford, 1981; Bucior et al., 2012; Smith and McCullers, 2014).”
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“On the other hand, an analogous type IV pilin protein, Tfp, of Pseudomonas aeruginosa has been shown to bind lung epithelial cells, leading to pathogenic effects in the host (452).”
Background
Metadata
- Authors
- Bucior, I., Pielage, J. F., & Engel, J. N.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Bucior, Iwona
- Pielage, Julia F.
- Engel, Joanne N.
- ORCID
- Engel, Joanne N.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-04-05
- Volume
- 8
- Issue
- 4
- Pages
- e1002616
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC3320588
- OpenAlex
- W2073200952
- Cited by
- 221
- References
- 66
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 13 · 2023: 21 · 2022: 15 · 2021: 13 · 2020: 17 · 2019: 17 · 2018: 15 · 2017: 20 · 2016: 14 · 2015: 10 · 2014: 24 · 2013: 14 · 2012: 2
- FWCI
- 6.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (P01AI053194, R01AI065902)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Keywords
- Pseudomonas aeruginosa, type IV pili, bacterial flagellum, bacterial adhesion, lung epithelium, N-glycans, heparan sulfate proteoglycans, phosphatidylinositol 3-kinase/Akt signaling, epidermal growth factor receptor, Shc adaptor protein, bacterial invasion, host-pathogen interaction, airway infection
- MeSH terms
- Bacterial Adhesion, Cell Line, Enzyme Activation, Flagella, Heparin, Humans, Lung, Mutation, Fimbriae, Bacterial, Pseudomonas aeruginosa, Pseudomonas Infections, Adhesins, Bacterial, Heparan Sulfate Proteoglycans, Phosphatidylinositol 3-Kinases, Respiratory Mucosa, Proto-Oncogene Proteins c-akt, ErbB Receptors
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