1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Invasion of Host Cells and Tissues by Uropathogenic Bacteria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • HTML
    175.44 Kb
  • PDF
    6.27 MB
  • XML
    154.95 Kb
  • Authors: Adam J. Lewis1, Amanda C. Richards2, Matthew A. Mulvey3
  • Editors: Matthew A. Mulvey4, Ann E. Stapleton5, David J. Klumpp6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112; 2: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112; 3: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112; 4: University of Utah, Salt Lake City, UT; 5: University of Washington, Seattle, WA; 6: Northwestern University, Chicago, IL
    • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
  • Received 21 September 2016 Accepted 21 November 2016 Published 16 December 2016
  • Matthew A. Mulvey, [email protected]
image of Invasion of Host Cells and Tissues by Uropathogenic Bacteria
    Preview this microbiology spectrum article:
    Preview Magnify
    Zoom in
    Zoomout

    Invasion of Host Cells and Tissues by Uropathogenic Bacteria, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/4/6/UTI-0026-2016-1.gif /docserver/preview/fulltext/microbiolspec/4/6/UTI-0026-2016-2.gif

  • Abstract:

    Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments. Translocation through host cells can facilitate bacterial dissemination within the urinary tract, while the establishment of stable intracellular bacterial populations may create reservoirs for relapsing and chronic urinary tract infections. Here we review the mechanisms and consequences of host cell invasion by uropathogenic bacteria, with consideration of the defenses that are brought to bear against facultative intracellular pathogens within the urinary tract. The relevance of host cell invasion to the pathogenesis of urinary tract infections in human patients is also assessed, along with some of the emerging treatment options that build upon our growing understanding of the infectious life cycle of uropathogenic and other uropathogens.

  • Citation: Lewis A, Richards A, Mulvey M. 2016. Invasion of Host Cells and Tissues by Uropathogenic Bacteria. Microbiol Spectrum 4(6):UTI-0026-2016. doi:10.1128/microbiolspec.UTI-0026-2016.

References

1. Bower JM, Eto DS, Mulvey MA. 2005. Covert operations of uropathogenic Escherichia coli within the urinary tract. Traffic 6:18–31. [PubMed]
2. Silva MT. 2012. Classical labeling of bacterial pathogens according to their lifestyle in the host: inconsistencies and alternatives. Front Microbiol 3:71. [PubMed]
3. Barber AE, Norton JP, Spivak AM, Mulvey MA. 2013. Urinary tract infections: current and emerging management strategies. Clin Infect Dis 57:719–724. [PubMed]
4. Dielubanza EJ, Schaeffer AJ. 2011. Urinary tract infections in women. Med Clin North Am 95:27–41. [PubMed]
5. Foxman B. 2014. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am 28:1–13. [PubMed]
6. Fukushi Y, Orikasa S, Kagayama M. 1979. An electron microscopic study of the interaction between vesical epitherlium and E. coli. Invest Urol 17:61–68. [PubMed]
7. McTaggart LA, Rigby RC, Elliott TS. 1990. The pathogenesis of urinary tract infections associated with Escherichia coli, Staphylococcus saprophyticus and S. epidermidis. J Med Microbiol 32:135–141. [PubMed]
8. Wakefield JS, Hicks RM. 1974. Erythrophagocytosis by the epithelial cells of the bladder. J Cell Sci 15:555–573. [PubMed]
9. Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ. 1998. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282:1494–1497. [PubMed]
10. Russell PW, Orndorff PE. 1992. Lesions in two Escherichia coli type 1 pilus genes alter pilus number and length without affecting receptor binding. J Bacteriol 174:5923–5935.
11. Jones CH, Pinkner JS, Roth R, Heuser J, Nicholes AV, Abraham SN, Hultgren SJ. 1995. FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci USA 92:2081–2085. [PubMed]
12. Zhou G, Mo WJ, Sebbel P, Min G, Neubert TA, Glockshuber R, Wu XR, Sun TT, Kong XP. 2001. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J Cell Sci 114:4095–4103. [PubMed]
13. Wu XR, Kong XP, Pellicer A, Kreibich G, Sun TT. 2009. Uroplakins in urothelial biology, function, and disease. Kidney Int 75:1153–1165. [PubMed]
14. Apodaca G. 2004. The uroepithelium: not just a passive barrier. Traffic 5:117–128. [PubMed]
15. Hu P, Meyers S, Liang FX, Deng FM, Kachar B, Zeidel ML, Sun TT. 2002. Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability. Am J Physiol Renal Physiol 283:F1200–F1207. [PubMed]
16. Acharya P, Beckel J, Ruiz WG, Wang E, Rojas R, Birder L, Apodaca G. 2004. Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium. Am J Physiol Renal Physiol 287:F305–F318. [PubMed]
17. Mulvey MA, Schilling JD, Hultgren SJ. 2001. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun 69:4572–4579. [PubMed]
18. Mulvey MA, Schilling JD, Martinez JJ, Hultgren SJ. 2000. Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. Proc Natl Acad Sci USA 97:8829–8835. [PubMed]
19. Kerrn MB, Struve C, Blom J, Frimodt-Moller N, Krogfelt KA. 2005. Intracellular persistence of Escherichia coli in urinary bladders from mecillinam-treated mice. J Antimicrob Chemother 55:383–386. [PubMed]
20. Schilling JD, Lorenz RG, Hultgren SJ. 2002. Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli. Infect Immun 70:7042–7049. [PubMed]
21. Schwartz DJ, Chen SL, Hultgren SJ, Seed PC. 2011. Population dynamics and niche distribution of uropathogenic Escherichia coli during acute and chronic urinary tract infection. Infect Immun 79:4250–4259. [PubMed]
22. Hvidberg H, Struve C, Krogfelt KA, Christensen N, Rasmussen SN, Frimodt-Moller N. 2000. Development of a long-term ascending urinary tract infection mouse model for antibiotic treatment studies. Antimicrob Agents Chemother 44:156–163. [PubMed]
23. Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, Hultgren SJ. 2004. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci USA 101:1333–1338. [PubMed]
24. Blango MG, Mulvey MA. 2010. Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics. Antimicrob Agents Chemother 54:1855–1863. [PubMed]
25. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. 2000. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J 19:2803–2812. [PubMed]
26. Eto DS, Sundsbak JL, Mulvey MA. 2006. Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli. Cell Microbiol 8:704–717. [PubMed]
27. Mysorekar IU, Hultgren SJ. 2006. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci USA 103:14170–14175. [PubMed]
28. Anderson GG, Palermo JJ, Schilling JD, Roth R, Heuser J, Hultgren SJ. 2003. Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301:105–107. [PubMed]
29. Blango MG, Ott EM, Erman A, Veranic P, Mulvey MA. 2014. Forced resurgence and targeting of intracellular uropathogenic Escherichia coli reservoirs. PLoS One 9:e93327. doi:10.1371/journal.pone.0093327.
30. Hunstad DA, Justice SS. 2010. Intracellular lifestyles and immune evasion strategies of uropathogenic Escherichia coli. Annu Rev Microbiol 64:203–221. [PubMed]
31. Justice SS, Hunstad DA, Seed PC, Hultgren SJ. 2006. Filamentation by Escherichia coli subverts innate defenses during urinary tract infection. Proc Natl Acad Sci USA 103:19884–19889. [PubMed]
32. Li B, Smith P, Horvath DJ Jr, Romesberg FE, Justice SS. 2010. SOS regulatory elements are essential for UPEC pathogenesis. Microbes Infect 12:662–668. [PubMed]
33. Hannan TJ, Mysorekar IU, Hung CS, Isaacson-Schmid ML, Hultgren SJ. 2010. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS Pathog 6:e1001042. doi:10.1371/journal.ppat.1001042. [PubMed]
34. Garofalo CK, Hooton TM, Martin SM, Stamm WE, Palermo JJ, Gordon JI, Hultgren SJ. 2007. Escherichia coli from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation. Infect Immun 75:52–60. [PubMed]
35. Barber AE, Norton JP, Wiles TJ, Mulvey MA. 2016. Strengths and limitations of model systems for the study of urinary tract infections and related pathologies. Microbiol Mol Biol Rev 80:351–367. [PubMed]
36. Barber AE, Mulvey MA. 2014. Reply to Kaye and Sobel. Clin Infect Dis 58:444–445. [PubMed]
37. Kaye D, Sobel JD. 2014. Persistence of intracellular bacteria in the urinary bladder. Clin Infect Dis 58:444. [PubMed]
38. Elliott TS, Reed L, Slack RC, Bishop MC. 1985. Bacteriology and ultrastructure of the bladder in patients with urinary tract infections. J Infect 11:191–199. [PubMed]
39. Lakeman MM, Roovers JP. 2016. Urinary tract infections in women with urogynaecological symptoms. Curr Opin Infect Dis 29:92–97. [PubMed]
40. Khasriya R, Sathiananthamoorthy S, Ismail S, Kelsey M, Wilson M, Rohn JL, Malone-Lee J. 2013. Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol 51:2054–2062. [PubMed]
41. Scott VC, Haake DA, Churchill BM, Justice SS, Kim JH. 2015. Intracellular bacterial communities: a potential etiology for chronic lower urinary tract symptoms. Urology 86:425–431. [PubMed]
42. Cheng Y, Chen Z, Gawthorne JA, Mukerjee C, Varettas K, Mansfield KJ, Schembri MA, Moore KH. 2016. Detection of intracellular bacteria in exfoliated urothelial cells from women with urge incontinence. Pathog Dis 74. [PubMed]
43. Kelley SP, Courtneidge HR, Birch RE, Contreras-Sanz A, Kelly MC, Durodie J, Peppiatt-Wildman CM, Farmer CK, Delaney MP, Malone-Lee J, Harber MA, Wildman SS. 2014. Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients? Springerplus 3:200. doi:10.1186/2193-1801-3-200.
44. Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ. 2007. Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med 4:e329. doi:10.1371/journal.pmed.0040329. [PubMed]
45. Robino L, Scavone P, Araujo L, Algorta G, Zunino P, Pirez MC, Vignoli R. 2014. Intracellular bacteria in the pathogenesis of Escherichia coli urinary tract infection in children. Clin Infect Dis 59:e158–e164. [PubMed]
46. Robino L, Scavone P, Araujo L, Algorta G, Zunino P, Vignoli R. 2013. Detection of intracellular bacterial communities in a child with Escherichia coli recurrent urinary tract infections. Pathog Dis 68:78–81. [PubMed]
47. Ikaheimo R, Siitonen A, Heiskanen T, Karkkainen U, Kuosmanen P, Lipponen P, Makela PH. 1996. Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin Infect Dis 22:91–99. [PubMed]
48. Russo TA, Stapleton A, Wenderoth S, Hooton TM, Stamm WE. 1995. Chromosomal restriction fragment length polymorphism analysis of Escherichia coli strains causing recurrent urinary tract infections in young women. J Infect Dis 172:440–445. [PubMed]
49. Brauner A, Jacobson SH, Kuhn I. 1992. Urinary Escherichia coli causing recurrent infections: a prospective follow-up of biochemical phenotypes. Clin Nephrol 38:318–323. [PubMed]
50. Jacobson SH, Kuhn I, Brauner A. 1992. Biochemical fingerprinting of urinary Escherichia coli causing recurrent infections in women with pyelonephritic renal scarring. Scand J Urol Nephrol 26:373–377. [PubMed]
51. Wang H, Liang FX, Kong XP. 2008. Characteristics of the phagocytic cup induced by uropathogenic Escherichia coli. J Histochem Cytochem 56:597–604. [PubMed]
52. Alonso A, Garcia-del Portillo F. 2004. Hijacking of eukaryotic functions by intracellular bacterial pathogens. Int Microbiol 7:181–191. [PubMed]
53. Wu X-R, Sun T-T, Medina JJ. 1996. In vitro binding of type 1-fimbriated Escherichia coli to uroplakins Ia and Ib: relation to urinary tract infections. Proc Natl Acad Sci USA 93:9630–9635. [PubMed]
54. Wankel B, Ouyang J, Guo X, Hadjiolova K, Miller J, Liao Y, Tham DK, Romih R, Andrade LR, Gumper I, Simon JP, Sachdeva R, Tolmachova T, Seabra MC, Fukuda M, Schaeren-Wiemers N, Hong WJ, Sabatini DD, Wu XR, Kong X, Kreibich G, Rindler MJ, Sun TT. 2016. Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells. Mol Biol Cell 27:1621–1634. [PubMed]
55. Khandelwal P, Ruiz WG, Apodaca G. 2010. Compensatory endocytosis in bladder umbrella cells occurs through an integrin-regulated and RhoA- and dynamin-dependent pathway. EMBO J 29:1961–1975. [PubMed]
56. Hicks RM. 1975. The mammalian bladder: an accommodating organ. Biol Rev Camb Philos Soc 50:1123. [PubMed]
57. Min G, Stolz M, Zhou G, Liang F, Sebbel P, Stoffler D, Glockshuber R, Sun TT, Aebi U, Kong XP. 2002. Localization of uroplakin Ia, the urothelial receptor for bacterial adhesin FimH, on the six inner domains of the 16 nm urothelial plaque particle. J Mol Biol 317:697–706. [PubMed]
58. Wang H, Min G, Glockshuber R, Sun T-T, Kong X-P. 2009. Uropathogenic E. coli adhesin-induced host cell receptor conformation changes: implications in transmembrane signaling transduction. J Mol Biol 392:352–361. [PubMed]
59. Mathai JC, Zhou EH, Yu W, Kim JH, Zhou G, Liao Y, Sun TT, Fredberg JJ, Zeidel ML. 2014. Hypercompliant apical membranes of bladder umbrella cells. Biophys J 107:1273–1279. [PubMed]
60. Thumbikat P, Berry RE, Zhou G, Billips BK, Yaggie RE, Zaichuk T, Sun T-T, Schaeffer AJ, Klumpp DJ. 2009. Bacteria-induced uroplakin signaling mediates bladder response to infection. PLoS Pathog 5:e1000415. doi:10.1371/journal.ppat.1000415.
61. Baorto DM, Gao Z, Malaviya R, Dustin ML, van der Merwe A, Lublin DM, Abraham SN. 1997. Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature 389:636–639. [PubMed]
62. Leusch HG, Drzeniek Z, Markos-Pusztai Z, Wagener C. 1991. Binding of Escherichia coli and Salmonella strains to members of the carcinoembryonic antigen family: differential binding inhibition by aromatic alpha-glycosides of mannose. Infect Immun 59:2051–2057. [PubMed]
63. Sauter SL, Rutherfurd SM, Wagener C, Shiveley JE, Hefta SA. 1991. Binding of nonspecific crossreacting antigen, a granulocyte membrane glycoprotein, to Escherichia coli expressing type 1 fimbriae. Infection and Immunity 59:2485–2493. [PubMed]
64. Gbarah A, Gahmberg CG, Ofek I, Jacobi U, Sharon N. 1991. Identification of the leukocyte adhesion molecules CD11 and CD18 as receptors for type 1-fimbriated (mannose-specific) Escherichia coli. Infect Immun 59:4524–4530. [PubMed]
65. Pouttu R, Puustinen T, Virkola R, Hacker J, Klemm P, Korhonen TK. 1999. Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the adhesiveness of meningitis-associated Escherichia coli to collagens. Mol Microbiol 31:1747–1757. [PubMed]
66. Kukkonen M, Raunio T, Virkola R, Lahteenmaki K, Makela PH, Klemm P, Clegg S, Korhonen TK. 1993. Basement membrane carbohydrate as a target for bacterial adhesion: binding of type I fimbriae of Salmonella enterica and Escherichia coli to laminin. Mol Microbiol 7:229–237. [PubMed]
67. Sokurenko EV, Courtney HS, Abraham SN, Klemm P, Hasty DL. 1992. Functional heterogeneity of type 1 fimbriae of Escherichia coli. InfectImmun 60:4709–4719. [PubMed]
68. Mossman KL, Mian MF, Lauzon NM, Gyles CL, Lichty B, Mackenzie R, Gill N, Ashkar AA. 2008. Cutting edge: FimH adhesin of type 1 fimbriae is a novel TLR4 ligand. J Immunol 181:6702–6706. [PubMed]
69. Hase K, Kawano K, Nochi T, Pontes GS, Fukuda S, Ebisawa M, Kadokura K, Tobe T, Fujimura Y, Kawano S, Yabashi A, Waguri S, Nakato G, Kimura S, Murakami T, Iimura M, Hamura K, Fukuoka S, Lowe AW, Itoh K, Kiyono H, Ohno H. 2009. Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. Nature 462:226–230. [PubMed]
70. Yu S, Lowe AW. 2009. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 fimbriae. BMC Gastroenterol 9:58. doi:10.1186/1471-230X-9-58. [PubMed]
71. Eto DS, Jones TA, Sundsbak JL, Mulvey MA. 2007. Integrin-mediated host cell invasion by type 1–piliated uropathogenic Escherichia coli. PLoS Pathog 3:e100. doi:10.1371/journal.ppat.0030100.
72. Ielasi FS, Alioscha-Perez M, Donohue D, Claes S, Sahli H, Schols D, Willaert RG. 2016. Lectin-glycan interaction network-based identification of host receptors of microbial pathogenic adhesins. MBio 7:e00584-16. doi:10.1128/mBio.00584-16. [PubMed]
73. Arnaout MA, Mahalingam B, Xiong JP. 2005. Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol 21:381–410. [PubMed]
74. Southgate J, Kennedy W, Hutton KA, Trejdosiewicz LK. 1995. Expression and in vitro regulation of integrins by normal human urothelial cells. Cell Adhes Commun 3:231–242. [PubMed]
75. Kanasaki K, Yu W, von Bodungen M, Larigakis JD, Kanasaki M, Ayala de la Pena F, Kalluri R, Hill WG. 2013. Loss of beta1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype. FASEB J 27:1950–1961. [PubMed]
76. Scibelli A, Roperto S, Manna L, Pavone LM, Tafuri S, Della Morte R, Staiano N. 2007. Engagement of integrins as a cellular route of invasion by bacterial pathogens. Vet J 173:482–491. [PubMed]
77. Hauck CR, Borisova M, Muenzner P. 2012. Exploitation of integrin function by pathogenic microbes. Curr Opin Cell Biol 24:637–644. [PubMed]
78. Elices MJ, Urry LA, Hemler ME. 1991. Receptor functions for the integrin VLA-3: fibronectin, collagen, and laminin binding are differentially influenced by Arg-Gly-Asp peptide and by divalent cations. J Cell Biol 112:169–181. [PubMed]
79. Xie B, Zhou G, Chan SY, Shapiro E, Kong XP, Wu XR, Sun TT, Costello CE. 2006. Distinct glycan structures of uroplakins Ia and Ib: structural basis for the selective binding of FimH adhesin to uroplakin Ia. J Biol Chem 281:14644–14653. [PubMed]
80. Litynska A, Przybylo M, Ksiazek D, Laidler P. 2000. Differences of alpha3beta1 integrin glycans from different human bladder cell lines. Acta Biochim Pol 47:427–434. [PubMed]
81. Litynska A, Pochec E, Hoja-Lukowicz D, Kremser E, Laidler P, Amoresano A, Monti C. 2002. The structure of the oligosaccharides of alpha3beta1 integrin from human ureter epithelium (HCV29) cell line. Acta Biochim Pol 49:491–500. [PubMed]
82. Eto DS, Gordon HB, Dhakal BK, Jones TA, Mulvey MA. 2008. Clathrin, AP-2, and the NPXY-binding subset of alternate endocytic adaptors facilitate FimH-mediated bacterial invasion of host cells. Cell Microbiol 10:2553–2567. [PubMed]
83. Martinez JJ, Hultgren SJ. 2002. Requirement of Rho-family GTPases in the invasion of type 1-piliated uropathogenic Escherichia coli. Cell Microbiol 4:19–28.
84. Shen XF, Teng Y, Sha KH, Wang XY, Yang XL, Guo XJ, Ren LB, Wang XY, Li J, Huang N. 2016. Dietary flavonoid luteolin attenuates uropathogenic Escherichia coli invasion of the urinary bladder. Biofactors [Epub ahead of print.] doi:10.1002/biof.1314.
85. Lewis AJ, Dhakal BK, Liu T, Mulvey MA. 2016. Histone deacetylase 6 regulates bladder architecture and host susceptibility to uropathogenic Escherichia coli. Pathogens 5:E20. doi:10.3390/pathogens5010020. [PubMed]
86. Dhakal BK, Mulvey MA. 2009. Uropathogenic Escherichia coli invades host cells via an HDAC6-modulated microtubule-dependent pathway. J Biol Chem 284:446–454. [PubMed]
87. Braun V, Niedergang F. 2006. Linking exocytosis and endocytosis during phagocytosis. Biol Cell 98:195–201. [PubMed]
88. Swanson JA. 2008. Shaping cups into phagosomes and macropinosomes. Nat Rev Mol Cell Biol 9:639–649. [PubMed]
89. Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. 2007. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med 13:625–630. [PubMed]
90. Song J, Bishop BL, Li G, Grady R, Stapleton A, Abraham SN. 2009. TLR4-mediated expulsion of bacteria from infected bladder epithelial cells. Proc Natl Acad Sci USA 106:14966–14971. [PubMed]
91. Guo X, Tu L, Gumper I, Plesken H, Novak EK, Chintala S, Swank RT, Pastores G, Torres P, Izumi T, Sun TT, Sabatini DD, Kreibich G. 2009. Involvement of vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes. Traffic 10:1350–1361. [PubMed]
92. Wang Z, Humphrey C, Frilot N, Wang G, Nie Z, Moniri NH, Daaka Y. 2011. Dynamin2- and endothelial nitric oxide synthase-regulated invasion of bladder epithelial cells by uropathogenic Escherichia coli. J Cell Biol 192:101–110. [PubMed]
93. Wang G, Moniri NH, Ozawa K, Stamler JS, Daaka Y. 2006. Nitric oxide regulates endocytosis by S-nitrosylation of dynamin. Proc Natl Acad Sci USA 103:1295–1300. [PubMed]
94. Lundberg JO, Ehren I, Jansson O, Adolfsson J, Lundberg JM, Weitzberg E, Alving K, Wiklund NP. 1996. Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis. Urology 48:700–702. [PubMed]
95. Svensson L, Marklund BI, Poljakovic M, Persson K. 2006. Uropathogenic Escherichia coli and tolerance to nitric oxide: the role of flavohemoglobin. J Urol 175:749–753.
96. Poljakovic M, Svensson ML, Svanborg C, Johansson K, Larsson B, Persson K. 2001. Escherichia coli-induced inducible nitric oxide synthase and cyclooxygenase expression in the mouse bladder and kidney. Kidney Int 59:893–904. [PubMed]
97. Bower JM, Gordon-Raagas HB, Mulvey MA. 2009. Conditioning of uropathogenic Escherichia coli for enhanced colonization of host. Infect Immun 77:2104–2112. [PubMed]
98. Bower JM, Mulvey MA. 2006. Polyamine-mediated resistance of uropathogenic Escherichia coli to nitrosative stress. J Bacteriol 188:928–933. [PubMed]
99. Li K, Feito MJ, Sacks SH, Sheerin NS. 2006. CD46 (membrane cofactor protein) acts as a human epithelial cell receptor for internalization of opsonized uropathogenic Escherichia coli. J Immunol 177:2543–2551. [PubMed]
100. Li K, Zhou W, Hong Y, Sacks SH, Sheerin NS. 2009. Synergy between type 1 fimbriae expression and C3 opsonisation increases internalisation of E. coli by human tubular epithelial cells. BMC Microbiol 9:64. doi:10.1186/1471-2180-9-64.
101. He XL, Wang Q, Peng L, Qu YR, Puthiyakunnon S, Liu XL, Hui CY, Boddu S, Cao H, Huang SH. 2015. Role of uropathogenic Escherichia coli outer membrane protein T in pathogenesis of urinary tract infection. Pathog Dis 73:ftv006. doi:10.1093/femspd/ftv006. [PubMed]
102. Kakkanat A, Totsika M, Schaale K, Duell BL, Lo AW, Phan MD, Moriel DG, Beatson SA, Sweet MJ, Ulett GC, Schembri MA. 2015. The role of H4 flagella in Escherichia coli ST131 virulence. Sci Rep 5:16149. doi:10.1038/srep16149.
103. Saldana Z, De la Cruz MA, Carrillo-Casas EM, Duran L, Zhang Y, Hernandez-Castro R, Puente JL, Daaka Y, Giron JA. 2014. Production of the Escherichia coli common pilus by uropathogenic E. coli is associated with adherence to HeLa and HTB-4 cells and invasion of mouse bladder urothelium. PLoS One 9:e101200. doi:10.1371/journal.pone.0101200.
104. Visvikis O, Boyer L, Torrino S, Doye A, Lemonnier M, Lores P, Rolando M, Flatau G, Mettouchi A, Bouvard D, Veiga E, Gacon G, Cossart P, Lemichez E. 2011. Escherichia coli producing CNF1 toxin hijacks Tollip to trigger Rac1-dependent cell invasion. Traffic 12:579–590. [PubMed]
105. Doye A, Mettouchi A, Bossis G, Clement R, Buisson-Touati C, Flatau G, Gagnoux L, Piechaczyk M, Boquet P, Lemichez E. 2002. CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion. Cell 111:553–564. [PubMed]
106. Feldmann F, Sorsa LJ, Hildinger K, Schubert S. 2007. The salmochelin siderophore receptor IroN contributes to invasion of urothelial cells by extraintestinal pathogenic Escherichia coli in vitro. Infect Immun 75:3183–3187. [PubMed]
107. Rana T, Hasan RJ, Nowicki S, Venkatarajan MS, Singh R, Urvil PT, Popov V, Braun WA, Popik W, Goodwin JS, Nowicki BJ. 2014. Complement protective epitopes and CD55-microtubule complexes facilitate the invasion and intracellular persistence of uropathogenic Escherichia coli. J Infect Dis 209:1066–1076. [PubMed]
108. Goluszko P, Popov V, Selvarangan R, Nowicki S, Pham T, Nowicki BJ. 1997. Dr fimbriae operon of uropathogenic Escherichia coli mediate microtubule-dependent invasion to the HeLa epithelial cell line. J Infect Dis 176:158–167. [PubMed]
109. Das M, Hart-Van Tassell A, Urvil PT, Lea S, Pettigrew D, Anderson KL, Samet A, Kur J, Matthews S, Nowicki S, Popov V, Goluszko P, Nowicki BJ. 2005. Hydrophilic domain II of Escherichia coli Dr fimbriae facilitates cell invasion. Infect Immun 73:6119–6126. [PubMed]
110. Servin AL. 2014. Pathogenesis of human diffusely adhering Escherichia coli expressing Afa/Dr adhesins (Afa/Dr DAEC): current insights and future challenges. Clin Microbiol Rev 27:823–869. [PubMed]
111. Wang C, Mendonsa GR, Symington JW, Zhang Q, Cadwell K, Virgin HW, Mysorekar IU. 2012. Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo. Proc Natl Acad Sci USA 109:11008–11013. [PubMed]
112. Miao Y, Li G, Zhang X, Xu H, Abraham SN. 2015. A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. Cell 161:1306–1319. [PubMed]
113. Dikshit N, Bist P, Fenlon SN, Pulloor NK, Chua CE, Scidmore MA, Carlyon JA, Tang BL, Chen SL, Sukumaran B. 2015. Intracellular uropathogenic E. coli exploits host Rab35 for iron acquisition and survival within urinary bladder cells. PLoS Pathog 11:e1005083. doi:10.1371/journal.ppat.1005083.
114. Berry RE, Klumpp DJ, Schaeffer AJ. 2009. Urothelial cultures support intracellular bacterial community formation by uropathogenic Escherichia coli. Infect Immun 77:2762–2772. [PubMed]
115. Romih R, Veranic P, Jezernik K. 1999. Actin filaments during terminal differentiation of urothelial cells in the rat urinary bladder. Histochem Cell Biol 112:375–380. [PubMed]
116. Fleming BA, Mulvey MA. 2016. Toxin-antitoxin systems as regulators of bacterial fitness and virulence, p 437–445. In de Bruijn FJ (ed), Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria. John Wiley & Sons, Hoboken, NJ.
117. Norton JP, Mulvey MA. 2012. Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli. PLoS Pathog 8:e1002954. doi:10.1371/journal.ppat.1002954.
118. Fiedoruk K, Daniluk T, Swiecicka I, Sciepuk M, Leszczynska K. 2015. Type II toxin-antitoxin systems are unevenly distributed among Escherichia coli phylogroups. Microbiology 161:158–167. [PubMed]
119. Chole RA, Faddis BT. 2002. Evidence for microbial biofilms in cholesteatomas. Arch Otolaryngol Head Neck Surg 128:1129–1133. [PubMed]
120. Justice SS, Lauer SR, Hultgren SJ, Hunstad DA. 2006. Maturation of intracellular Escherichia coli communities requires SurA. Infect Immun 74:4793–4800. [PubMed]
121. Anderson GG, Goller CC, Justice S, Hultgren SJ, Seed PC. 2010. Polysaccharide capsule and sialic acid-mediated regulation promote biofilm-like intracellular bacterial communities during cystitis. Infect Immun 78:963–975. [PubMed]
122. Wright KJ, Seed PC, Hultgren SJ. 2007. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol 9:2230–2241. [PubMed]
123. Goller CC, Seed PC. 2010. Revisiting the Escherichia coli polysaccharide capsule as a virulence factor during urinary tract infection: contribution to intracellular biofilm development. Virulence 1:333–337. [PubMed]
124. Nicholson TF, Watts KM, Hunstad DA. 2009. OmpA of uropathogenic Escherichia coli promotes postinvasion pathogenesis of cystitis. Infect Immun 77:5245–5251. [PubMed]
125. Justice SS, Li B, Downey JS, Dabdoub SM, Brockson ME, Probst GD, Ray WC, Goodman SD. 2012. Aberrant community architecture and attenuated persistence of uropathogenic Escherichia coli in the absence of individual IHF subunits. PloS One 7:e48349. [PubMed]
126. Hadjifrangiskou M, Kostakioti M, Chen SL, Henderson JP, Greene SE, Hultgren SJ. 2011. A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Mol Microbiol 80:1516–1529. [PubMed]
127. Kulesus RR, Diaz-Perez K, Slechta ES, Eto DS, Mulvey MA. 2008. Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli. Infect Immun 76:3019–3026. [PubMed]
128. Shaffer CL, Zhang EW, Dudley AG, Dixon BR, Guckes KR, Breland EJ, Floyd KA, Casella DP, Algood HM, Clayton DB, Hadjifrangiskou M. 2016. Purine biosynthesis metabolically constrains intracellular survival of uropathogenic E. coli. Infect Immun. [Epub ahead of print.] doi:10.1128/IAI.00471-16.
129. Conover MS, Hadjifrangiskou M, Palermo JJ, Hibbing ME, Dodson KW, Hultgren SJ. 2016. Metabolic requirements of Escherichia coli in intracellular bacterial communities during urinary tract infection pathogenesis. MBio 7:e00104-16. doi:10.1128/mBio.00104-16.
130. Reigstad CS, Hultgren SJ, Gordon JI. 2007. Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled. J Biol Chem 282:21259–21267. [PubMed]
131. Kurimura Y, Nishitani C, Ariki S, Saito A, Hasegawa Y, Takahashi M, Hashimoto J, Takahashi S, Tsukamoto T, Kuroki Y. 2012. Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract. J Biol Chem 287:39578–39588. [PubMed]
132. Zasloff M. 2007. Antimicrobial peptides, innate immunity, and the normally sterile urinary tract. J Am Soc Nephrol 18:2810–2816. [PubMed]
133. Corthesy B. 2010. Role of secretory immunoglobulin A and secretory component in the protection of mucosal surfaces. Future Microbiol 5:817–829. [PubMed]
134. Spencer JD, Schwaderer AL, Wang H, Bartz J, Kline J, Eichler T, DeSouza KR, Sims-Lucas S, Baker P, Hains DS. 2013. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney Int 83:615–625. [PubMed]
135. Bates JM, Raffi HM, Prasadan K, Mascarenhas R, Laszik Z, Maeda N, Hultgren SJ, Kumar S. 2004. Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication. Kidney Int 65:791–797. [PubMed]
136. Mo L, Zhu XH, Huang HY, Shapiro E, Hasty DL, Wu XR. 2004. Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli. Am J Physiol Renal Physiol 286:F795–F802. [PubMed]
137. Wood MW, Breitschwerdt EB, Nordone SK, Linder KE, Gookin JL. 2012. Uropathogenic E. coli promote a paracellular urothelial barrier defect characterized by altered tight junction integrity, epithelial cell sloughing and cytokine release. J Comp Pathol 147:11–19. [PubMed]
138. Klumpp DJ, Rycyk MT, Chen MC, Thumbikat P, Sengupta S, Schaeffer AJ. 2006. Uropathogenic Escherichia coli induces extrinsic and intrinsic cascades to initiate urothelial apoptosis. Infect Immun 74:5106–5113. [PubMed]
139. Veranic P, Jezernik K. 2001. Succession of events in desquamation of superficial urothelial cells as a response to stress induced by prolonged constant illumination. Tissue Cell 33:280–285. [PubMed]
140. Jezernik K, Sterle M, Batista U. 1997. The distinct steps of cell detachment during development of mouse uroepithelial cells in the bladder. Cell Biol Int 21:1–6. [PubMed]
141. Aronson M, Medalia O, Amichay D, Nativ O. 1988. Endotoxin-induced shedding of viable uroepithelial cells is an antimicrobial defense mechanism. Infect Immun 56:1615–1617. [PubMed]
142. Wiles TJ, Dhakal BK, Eto DS, Mulvey MA. 2008. Inactivation of host Akt/protein kinase B signaling by bacterial pore-forming toxins. Mol Biol Cell 19:1427–1438. [PubMed]
143. Smith YC, Grande KK, Rasmussen SB, O’Brien AD. 2006. Novel three-dimensional organoid model for evaluation of the interaction of uropathogenic Escherichia coli with terminally differentiated human urothelial cells. Infect Immun 74:750–757. [PubMed]
144. Smith YC, Rasmussen SB, Grande KK, Conran RM, O’Brien AD. 2008. Hemolysin of uropathogenic Escherichia coli evokes extensive shedding of the uroepithelium and hemorrhage in bladder tissue within the first 24 hours after intraurethral inoculation of mice. Infect Immun 76:2978–2990. [PubMed]
145. Dhakal BK, Mulvey MA. 2012. The UPEC pore-forming toxin alpha-hemolysin triggers proteolysis of host proteins to disrupt cell adhesion, inflammatory, and survival pathways. Cell Host Microbe 11:58–69. [PubMed]
146. Mills M, Meysick KC, O’Brien AD. 2000. Cytotoxic necrotizing factor type 1 of uropathogenic Escherichia coli kills cultured human uroepithelial 5637 cells by an apoptotic mechanism. Infect Immun 68:5869–5880. [PubMed]
147. Mysorekar IU, Isaacson-Schmid M, Walker JN, Mills JC, Hultgren SJ. 2009. Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection. Cell Host Microbe 5:463–475. [PubMed]
148. Mysorekar IU, Mulvey MA, Hultgren SJ, Gordon JI. 2002. Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli. J Biol Chem 277:7412–7419. [PubMed]
149. Veranic P, Erman A, Kerec-Kos M, Bogataj M, Mrhar A, Jezernik K. 2009. Rapid differentiation of superficial urothelial cells after chitosan-induced desquamation. Histochem Cell Biol 131:129–139. [PubMed]
150. Shin K, Lee J, Guo N, Kim J, Lim A, Qu L, Mysorekar IU, Beachy PA. 2011. Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472:110–114. [PubMed]
151. Lin AE, Beasley FC, Olson J, Keller N, Shalwitz RA, Hannan TJ, Hultgren SJ, Nizet V. 2015. Role of hypoxia inducible factor-1α (HIF-1α) in innate defense against uropathogenic Escherichia coli infection. PLoS Pathog 11:e1004818. doi:10.1371/journal.ppat.1004818.
152. Chromek M, Slamova Z, Bergman P, Kovacs L, Podracka L, Ehren I, Hokfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A. 2006. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12:636–641. [PubMed]
153. Danka ES, Hunstad DA. 2015. Cathelicidin augments epithelial receptivity and pathogenesis in experimental Escherichia coli cystitis. J Infect Dis 211:1164–1173. [PubMed]
154. Miao Y, Wu J, Abraham SN. 2016. Ubiquitination of innate immune regulator TRAF3 orchestrates expulsion of intracellular bacteria by exocyst complex. Immunity 45:94–105. [PubMed]
155. Khandige S, Asferg CA, Rasmussen KJ, Larsen MJ, Overgaard M, Andersen TE, Moller-Jensen J. 2016. DamX controls reversible cell morphology switching in uropathogenic Escherichia coli. MBio 7:e00642-16. doi:10.1128/mBio.00642-16. [PubMed]
156. Horvath DJ Jr, Li B, Casper T, Partida-Sanchez S, Hunstad DA, Hultgren SJ, Justice SS. 2011. Morphological plasticity promotes resistance to phagocyte killing of uropathogenic Escherichia coli. Microbes Infect 13:426–437. [PubMed]
157. Nazareth H, Genagon SA, Russo TA. 2007. Extraintestinal pathogenic Escherichia coli survives within neutrophils. Infect Immun 75:2776–2785. [PubMed]
158. Bokil NJ, Totsika M, Carey AJ, Stacey KJ, Hancock V, Saunders BM, Ravasi T, Ulett GC, Schembri MA, Sweet MJ. 2011. Intramacrophage survival of uropathogenic Escherichia coli: differences between diverse clinical isolates and between mouse and human macrophages. Immunobiology 216:1164–1171. [PubMed]
159. Shepherd M, Achard ME, Idris A, Totsika M, Phan MD, Peters KM, Sarkar S, Ribeiro CA, Holyoake LV, Ladakis D, Ulett GC, Sweet MJ, Poole RK, McEwan AG, Schembri MA. 2016. The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection. Sci Rep 6:35285. [PubMed]
160. Mavromatis CH, Bokil NJ, Totsika M, Kakkanat A, Schaale K, Cannistraci CV, Ryu T, Beatson SA, Ulett GC, Schembri MA, Sweet MJ, Ravasi T. 2015. The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions. Cell Microbiol 17:730–746. [PubMed]
161. Qualman SJ, Gupta PK, Mendelsohn G. 1984. Intracellular Escherichia coli in urinary malakoplakia: a reservoir of infection and its therapeutic implications. Am J Clin Pathol 81:35–42. [PubMed]
162. Maderazo EG, Berlin BB, Morhardt C. 1979. Treatment of malakoplakia with trimethoprim-sulfamethoxazole. Urology 13:70–73.
163. Stanton MJ, Maxted W. 1981. Malacoplakia: a study of the literature and current concepts of pathogenesis, diagnosis and treatment. J Urol 125:139–146. [PubMed]
164. Mora-Bau G, Platt AM, van Rooijen N, Randolph GJ, Albert ML, Ingersoll MA. 2015. Macrophages subvert adaptive immunity to urinary tract infection. PLoS Pathog 11:e1005044. doi:10.1371/journal.ppat.1005044.
165. Palmer LM, Reilly TJ, Utsalo SJ, Donnenberg MS. 1997. Internalization of Escherichia coli by human renal epithelial cells is associated with tyrosine phosphorylation of specific host cell proteins. Infect Immun 65:2570–2575. [PubMed]
166. Warren JW, Mobley HL, Trifillis AL. 1988. Internalization of Escherichia coli into human renal tubular epithelial cells. J Infect Dis 158:221–223. [PubMed]
167. Donnenberg MS, Newman B, Utsalo SJ, Trifillis AL, Hebel JR, Warren JW. 1994. Internalization of Escherichia coli into human kidney epithelial cells: comparison of fecal and pyelonephritis-associated strains. J Infect Dis 169:831–838. [PubMed]
168. Chassin C, Vimont S, Cluzeaud F, Bens M, Goujon JM, Fernandez B, Hertig A, Rondeau E, Arlet G, Hornef MW, Vandewalle A. 2008. TLR4 facilitates translocation of bacteria across renal collecting duct cells. J Am Soc Nephrol 19:2364–2374. [PubMed]
169. Chassin C, Tourneur E, Bens M, Vandewalle A. 2011. A role for collecting duct epithelial cells in renal antibacterial defences. Cell Microbiol 13:1107–1113. [PubMed]
170. Szemiako K, Krawczyk B, Samet A, Sledzinska A, Nowicki B, Nowicki S, Kur J. 2013. A subset of two adherence systems, acute pro-inflammatory pap genes and invasion coding dra, fim, or sfa, increases the risk of Escherichia coli translocation to the bloodstream. Eur J Clin Microbiol Infect Dis 32:1579–1582. [PubMed]
171. Springall T, Sheerin NS, Abe K, Holers VM, Wan H, Sacks SH. 2001. Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli. Nat Med 7:801–806. [PubMed]
172. Choudhry N, Li K, Zhang T, Wu KY, Song Y, Farrar CA, Wang N, Liu CF, Peng Q, Wu W, Sacks SH, Zhou W. 2016. The complement factor 5a receptor 1 has a pathogenic role in chronic inflammation and renal fibrosis in a murine model of chronic pyelonephritis. Kidney Int 90:540–554. [PubMed]
173. Pichon C, Hechard C, du Merle L, Chaudray C, Bonne I, Guadagnini S, Vandewalle A, Le Bouguenec C. 2009. Uropathogenic Escherichia coli AL511 requires flagellum to enter renal collecting duct cells. Cell Microbiol 11:616–628. [PubMed]
174. Bens M, Vimont S, Ben Mkaddem S, Chassin C, Goujon JM, Balloy V, Chignard M, Werts C, Vandewalle A. 2014. Flagellin/TLR5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic Escherichia coli. Cell Microbiol 16:1503–1517. [PubMed]
175. Szabados F, Kleine B, Anders A, Kaase M, Sakinc T, Schmitz I, Gatermann S. 2008. Staphylococcus saprophyticus ATCC 15305 is internalized into human urinary bladder carcinoma cell line 5637. FEMS Microbiol Lett 285:163–169. [PubMed]
176. Leclercq SY, Sullivan MJ, Ipe DS, Smith JP, Cripps AW, Ulett GC. 2016. Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and beta-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence. Sci Rep 6:29000. doi:10.1038/srep29000.
177. Horsley H, Malone-Lee J, Holland D, Tuz M, Hibbert A, Kelsey M, Kupelian A, Rohn JL. 2013. Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection. PLoS One 8:e83637. doi:10.1371/journal.pone.0083637.
178. Chippendale GR, Warren JW, Trifillis AL, Mobley HL. 1994. Internalization of Proteus mirabilis by human renal epithelial cells. Infect Immun 62:3115–3121. [PubMed]
179. Schaffer JN, Norsworthy AN, Sun TT, Pearson MM. 2016. Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation. Proc Natl Acad Sci USA 113:4494–4499. [PubMed]
180. Alamuri P, Lower M, Hiss JA, Himpsl SD, Schneider G, Mobley HL. 2010. Adhesion, invasion, and agglutination mediated by two trimeric autotransporters in the human uropathogen Proteus mirabilis. Infect Immun 78:4882–4894. [PubMed]
181. Liu MC, Kuo KT, Chien HF, Tsai YL, Liaw SJ. 2015. New aspects of RpoE in uropathogenic Proteus mirabilis. Infect Immun 83:966–977. [PubMed]
182. Kurihara S, Sakai Y, Suzuki H, Muth A, Phanstiel Ot, Rather PN. 2013. Putrescine importer PlaP contributes to swarming motility and urothelial cell invasion in Proteus mirabilis. J Biol Chem 288:15668–15676. [PubMed]
183. Allison C, Coleman N, Jones PL, Hughes C. 1992. Ability of Proteus mirabilis to invade human urothelial cells is coupled to motility and swarming differentiation. Infect Immun 60:4740–4746. [PubMed]
184. Oelschlaeger TA, Tall BD. 1997. Invasion of cultured human epithelial cells by Klebsiella pneumoniae isolated from the urinary tract. Infect Immun 65:2950–2958. [PubMed]
185. Rosen DA, Pinkner JS, Walker JN, Elam JS, Jones JM, Hultgren SJ. 2008. Molecular variations in Klebsiella pneumoniae and Escherichia coli FimH affect function and pathogenesis in the urinary tract. Infect Immun 76:3346–3356. [PubMed]
186. Fumagalli O, Tall BD, Schipper C, Oelschlaeger TA. 1997. N-glycosylated proteins are involved in efficient internalization of Klebsiella pneumoniae by cultured human epithelial cells. Infect Immun 65:4445–4451. [PubMed]
187. Rosen DA, Pinkner JS, Jones JM, Walker JN, Clegg S, Hultgren SJ. 2008. Utilization of an intracellular bacterial community pathway in Klebsiella pneumoniae urinary tract infection and the effects of FimK on type 1 pilus expression. Infect Immun 76:3337–3345. [PubMed]
188. Croxall G, Weston V, Joseph S, Manning G, Cheetham P, McNally A. 2011. Increased human pathogenic potential of Escherichia coli from polymicrobial urinary tract infections in comparison to isolates from monomicrobial culture samples. J Med Microbiol 60:102–109. [PubMed]
189. Mydock-McGrane L, Cusumano Z, Han Z, Binkley J, Kostakioti M, Hannan T, Pinkner JS, Klein RD, Kalas V, Crowley J, Rath NP, Hultgren SJ, Janetka JW. 2016. Anti-virulence C-mannosides as antibiotic-sparing, oral therapeutics for urinary tract infections. J Med Chem 59:9390–9408. [PubMed]
190. Greene SE, Pinkner JS, Chorell E, Dodson KW, Shaffer CL, Conover MS, Livny J, Hadjifrangiskou M, Almqvist F, Hultgren SJ. 2014. Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli. MBio 5:e02038. doi:10.1128/mBio.02038-14.
191. Chahales P, Hoffman PS, Thanassi DG. 2016. Nitazoxanide inhibits pilus biogenesis by interfering with folding of the usher protein in the outer membrane. Antimicrob Agents Chemother 60:2028–2038. [PubMed]
192. Maki KC, Kaspar KL, Khoo C, Derrig LH, Schild AL, Gupta K. 2016. Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection. Am J Clin Nutr 103:1434–1442. [PubMed]
193. Rafsanjany N, Senker J, Brandt S, Dobrindt U, Hensel A. 2015. In vivo consumption of cranberry exerts ex vivo antiadhesive activity against fimh-dominated uropathogenic Escherichia coli: a combined in vivo, ex vivo, and in vitro study of an extract from vaccinium macrocarpon. J Agric Food Chem 63:8804–8818. [PubMed]
194. Hotchkiss AT Jr, Nunez A, Strahan GD, Chau HK, White AK, Marais JP, Hom K, Vakkalanka MS, Di R, Yam KL, Khoo C. 2015. Cranberry xyloglucan structure and inhibition of Escherichia coli adhesion to epithelial cells. J Agric Food Chem 63:5622–5633. [PubMed]
195. Vollmerhausen TL, Ramos NL, Dzung DT, Brauner A. 2013. Decoctions from Citrus reticulata blanco seeds protect the uroepithelium against Escherichia coli invasion. J Ethnopharmacol 150:770–774. [PubMed]
196. Erman A, Kerec Kos M, Zakelj S, Resnik N, Romih R, Veranic P. 2013. Correlative study of functional and structural regeneration of urothelium after chitosan-induced injury. Histochem Cell Biol 140:521–531. [PubMed]
197. Wagers PO, Tiemann KM, Shelton KL, Kofron WG, Panzner MJ, Wooley KL, Youngs WJ, Hunstad DA. 2015. Imidazolium salts as small-molecule urinary bladder exfoliants in a murine model. Antimicrob Agents Chemother 59:5494–5502. [PubMed]
198. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. 2015. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43:D447–452. [PubMed]
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.UTI-0026-2016
2016-12-16
2020-01-21

Abstract:

Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments. Translocation through host cells can facilitate bacterial dissemination within the urinary tract, while the establishment of stable intracellular bacterial populations may create reservoirs for relapsing and chronic urinary tract infections. Here we review the mechanisms and consequences of host cell invasion by uropathogenic bacteria, with consideration of the defenses that are brought to bear against facultative intracellular pathogens within the urinary tract. The relevance of host cell invasion to the pathogenesis of urinary tract infections in human patients is also assessed, along with some of the emerging treatment options that build upon our growing understanding of the infectious life cycle of uropathogenic and other uropathogens.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/microbiolspec/4/6/UTI-0026-2016.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.UTI-0026-2016&mimeType=html&fmt=ahah

Figures

Invasion of Host Cells and Tissues by Uropathogenic Bacteria
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-1,webId=/content/author/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-1,properties={foaf_givenname=Adam J., foaf_name=Adam J. Lewis, foaf_surname=Lewis, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-2,webId=/content/author/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-2,properties={foaf_givenname=Amanda C., foaf_name=Amanda C. Richards, foaf_surname=Richards, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-aff2]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-3,webId=/content/author/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-3,properties={foaf_givenname=Matthew A., foaf_name=Matthew A. Mulvey, foaf_surname=Mulvey, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.UTI-0026-2016-aff3]]}]]
Citation: Lewis A, Richards A, Mulvey M. 2016. Invasion of host cells and tissues by uropathogenic bacteria. microbiolspec 4(6): doi:10.1128/microbiolspec.UTI-0026-2016
/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig1
FIGURE 1

Type 1 pili mediate UPEC entry into bladder epithelial cells. High-resolution deep-etch electron microscopy image showing UPEC (yellow) bound to a mouse bladder umbrella cell (blue) via multiple type 1 pili. Close-up view of a type 1 pilus, showing the 3-nm-wide FimH-containing tip fibrillum structure (arrowhead). Close-up view of the 16-nm-wide hexagonal uroplakin complexes that are embedded within the umbrella cell asymmetric unit membrane (AUM). High-resolution freeze-fracture/deep-etch electron microscopy images showing the AUM enveloping bound UPEC. Scale bars = 0.5 μm. Images are reprinted from ( 18 ) and ( 9 ) with permission of the publishers.

microbiolspec/4/6/UTI-0026-2016-fig1_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig1.gif
Image of FIGURE 1

Click to view

FIGURE 1

Type 1 pili mediate UPEC entry into bladder epithelial cells. High-resolution deep-etch electron microscopy image showing UPEC (yellow) bound to a mouse bladder umbrella cell (blue) via multiple type 1 pili. Close-up view of a type 1 pilus, showing the 3-nm-wide FimH-containing tip fibrillum structure (arrowhead). Close-up view of the 16-nm-wide hexagonal uroplakin complexes that are embedded within the umbrella cell asymmetric unit membrane (AUM). High-resolution freeze-fracture/deep-etch electron microscopy images showing the AUM enveloping bound UPEC. Scale bars = 0.5 μm. Images are reprinted from ( 18 ) and ( 9 ) with permission of the publishers.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig2
FIGURE 2

Localization of UPEC within the bladder urothelium. Confocal images of tissue sections from infected mouse bladders show IBCs (green) within umbrella cells (UC). F-actin (red) is sparse within these host cells but dense within the underlying immature cells (IC). A single bacterium, localized within a LAMP-1-positive compartment (blue) and surrounded by F-actin, is visible within one of the immature cells (box). Images show magnified views of the area that is boxed in (B). Figures are reprinted from ( 26 ) with permission of the publisher.

microbiolspec/4/6/UTI-0026-2016-fig2_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig2.gif
Image of FIGURE 2

Click to view

FIGURE 2

Localization of UPEC within the bladder urothelium. Confocal images of tissue sections from infected mouse bladders show IBCs (green) within umbrella cells (UC). F-actin (red) is sparse within these host cells but dense within the underlying immature cells (IC). A single bacterium, localized within a LAMP-1-positive compartment (blue) and surrounded by F-actin, is visible within one of the immature cells (box). Images show magnified views of the area that is boxed in (B). Figures are reprinted from ( 26 ) with permission of the publisher.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig3
FIGURE 3

The efflux and filamentation of UPEC coincident with the exfoliation of IBC-containing umbrella cells. Scanning electron microscopy images show filamentous forms of UPEC, as well as their normal-sized counterparts, emerging from within IBCs. Image from a hematoxylin- and eosin-stained bladder section highlights the ability of filamentous UPEC forms to extend long distances through umbrella cells. Confocal image shows an IBC (blue) in close association with cytokeratin intermediate filaments (green) within an umbrella cell that is undergoing exfoliation. LAMP-1-positive compartments are red. Scale bars = 5 μm (A–C); 10 μm (D, E). Images are from mouse bladders recovered 6 hours after transurethral inoculation with UPEC. The figures are modified from ( 26 ) or reprinted from ( 17 ) with permission of the publishers.

microbiolspec/4/6/UTI-0026-2016-fig3_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig3.gif
Image of FIGURE 3

Click to view

FIGURE 3

The efflux and filamentation of UPEC coincident with the exfoliation of IBC-containing umbrella cells. Scanning electron microscopy images show filamentous forms of UPEC, as well as their normal-sized counterparts, emerging from within IBCs. Image from a hematoxylin- and eosin-stained bladder section highlights the ability of filamentous UPEC forms to extend long distances through umbrella cells. Confocal image shows an IBC (blue) in close association with cytokeratin intermediate filaments (green) within an umbrella cell that is undergoing exfoliation. LAMP-1-positive compartments are red. Scale bars = 5 μm (A–C); 10 μm (D, E). Images are from mouse bladders recovered 6 hours after transurethral inoculation with UPEC. The figures are modified from ( 26 ) or reprinted from ( 17 ) with permission of the publishers.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig4
FIGURE 4

UPEC invasion of bladder epithelial cells. Model depicts host and bacterial factors that have been identified as regulators of bladder cell invasion by UPEC. Potential therapeutics are also indicated. The host factors that can modulate the FimH-dependent entry of UPEC into bladder cells are interconnected. The image in (B) was created using the STRING database (version 10.0) of known and predicted protein-protein interactions ( 198 ). Line thickness indicates the strength of the supporting data.

microbiolspec/4/6/UTI-0026-2016-fig4_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig4.gif
Image of FIGURE 4

Click to view

FIGURE 4

UPEC invasion of bladder epithelial cells. Model depicts host and bacterial factors that have been identified as regulators of bladder cell invasion by UPEC. Potential therapeutics are also indicated. The host factors that can modulate the FimH-dependent entry of UPEC into bladder cells are interconnected. The image in (B) was created using the STRING database (version 10.0) of known and predicted protein-protein interactions ( 198 ). Line thickness indicates the strength of the supporting data.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/microbiolspec/10.1128/microbiolspec.UTI-0026-2016.fig5
FIGURE 5

The fates of UPEC following entry into bladder epithelial cells. See text for details.

microbiolspec/4/6/UTI-0026-2016-fig5_thmb.gif
microbiolspec/4/6/UTI-0026-2016-fig5.gif
Image of FIGURE 5

Click to view

FIGURE 5

The fates of UPEC following entry into bladder epithelial cells. See text for details.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.UTI-0026-2016
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error