sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic

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Recent years have seen an increasing emphasis placed on the role of small RNAs (sRNAs) in the regulation of bacterial gene expression and stress adaptation. The advent of high-throughput sequencing methods has now made it possible to directly monitor the appearance of potentially virulence-associated sRNAs that may contribute to rapid adaptation of the pathogen to a changing environment during infection. Uropathogenic Escherichia coli (UPEC) are presumably exposed to a deluge of stimuli from epithelial cell contact, urine and host immune factors and we asked if any regulatory sRNAs would play a role in the transition of UPEC from the extracellular niche to the intracellular one. This study employs co-immunoprecipitation using the RNA chaperone Hfq to identify novel virulence-associated sRNAs in intracellular UPEC, followed by high-throughput RNA-seq. We report the identification of a novel sRNA that we designate PapR (P-fimbriae regulator) and elaborate on this discovery by demonstrating a role for PapR in regulation of P-fimbriae—a UPEC surface virulence factor. The results presented in this study offer new insights into the molecular mechanisms of UPEC pathogenesis and a role for sRNA mediated regulation of virulence factors.

Vyšlo v časopise: sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005109
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005109

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Zdroje

1. Brzuszkiewicz E, Bruggemann H, Liesegang H, Emmerth M, Olschlager T, Nagy G, et al. How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc Natl Acad Sci U S A. 2006;103(34):12879–84. doi: 10.1073/pnas.0603038103 16912116; PubMed Central PMCID: PMC1568941.

2. Anderson GG, Dodson KW, Hooton TM, Hultgren SJ. Intracellular bacterial communities of uropathogenic Escherichia coli in urinary tract pathogenesis. Trends in microbiology. 2004;12(9):424–30. doi: 10.1016/j.tim.2004.07.005 15337164.

3. Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, et al. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci U S A. 2004;101(5):1333–8. doi: 10.1073/pnas.0308125100 14739341; PubMed Central PMCID: PMC337053.

4. Justice SS, Hunstad DA, Seed PC, Hultgren SJ. Filamentation by Escherichia coli subverts innate defenses during urinary tract infection. Proc Natl Acad Sci U S A. 2006;103(52):19884–9. doi: 10.1073/pnas.0606329104 17172451; PubMed Central PMCID: PMC1750882.

5. Anderson GG, Palermo JJ, Schilling JD, Roth R, Heuser J, Hultgren SJ. Intracellular bacterial biofilm-like pods in urinary tract infections. Science. 2003;301(5629):105–7. doi: 10.1126/science.1084550 12843396.

6. Andersen TE, Khandige S, Madelung M, Brewer J, Kolmos HJ, Moller-Jensen J. Escherichia coli uropathogenesis in vitro: invasion, cellular escape, and secondary infection analyzed in a human bladder cell infection model. Infect Immun. 2012;80(5):1858–67. doi: 10.1128/IAI.06075-11 22354025; PubMed Central PMCID: PMC3347433.

7. Johnson DE, Lockatell CV, Russell RG, Hebel JR, Island MD, Stapleton A, et al. Comparison of Escherichia coli strains recovered from human cystitis and pyelonephritis infections in transurethrally challenged mice. Infect Immun. 1998;66(7):3059–65. 9632566; PubMed Central PMCID: PMC108313.

8. Justice SS, Hunstad DA. UPEC hemolysin: more than just for making holes. Cell host & microbe. 2012;11(1):4–5. doi: 10.1016/j.chom.2012.01.001 22264508; PubMed Central PMCID: PMC3267088.

9. Rippere-Lampe KE, Lang M, Ceri H, Olson M, Lockman HA, O'Brien AD. Cytotoxic necrotizing factor type 1-positive Escherichia coli causes increased inflammation and tissue damage to the prostate in a rat prostatitis model. Infect Immun. 2001;69(10):6515–9. doi: 10.1128/IAI.69.10.6515-c6519.2001 11553597; PubMed Central PMCID: PMC98788.

10. Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, et al. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. Proc Natl Acad Sci U S A. 2006;103(15):5977–82. doi: 10.1073/pnas.0600938103 16585510; PubMed Central PMCID: PMC1424661.

11. Melican K, Sandoval RM, Kader A, Josefsson L, Tanner GA, Molitoris BA, et al. Uropathogenic Escherichia coli P and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction. PLoS pathogens. 2011;7(2):e1001298. doi: 10.1371/journal.ppat.1001298 21383970; PubMed Central PMCID: PMC3044688.

12. Hagberg L, Hull R, Hull S, Falkow S, Freter R, Svanborg Eden C. Contribution of adhesion to bacterial persistence in the mouse urinary tract. Infect Immun. 1983;40(1):265–72. 6131870; PubMed Central PMCID: PMC264844.

13. Lane MC, Mobley HL. Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney international. 2007;72(1):19–25. doi: 10.1038/sj.ki.5002230 17396114.

14. Korhonen TK, Virkola R, Holthofer H. Localization of binding sites for purified Escherichia coli P fimbriae in the human kidney. Infect Immun. 1986;54(2):328–32. 2876959; PubMed Central PMCID: PMC260164.

15. Blyn LB, Braaten BA, White-Ziegler CA, Rolfson DH, Low DA. Phase-variation of pyelonephritis-associated pili in Escherichia coli: evidence for transcriptional regulation. The EMBO journal. 1989;8(2):613–20. 2656260; PubMed Central PMCID: PMC400848.

16. Braaten BA, Nou X, Kaltenbach LS, Low DA. Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coli. Cell. 1994;76(3):577–88. 7906204.

17. Forsman K, Goransson M, Uhlin BE. Autoregulation and multiple DNA interactions by a transcriptional regulatory protein in E. coli pili biogenesis. The EMBO journal. 1989;8(4):1271–7. 2568258; PubMed Central PMCID: PMC400944.

18. Mraheil MA, Billion A, Mohamed W, Mukherjee K, Kuenne C, Pischimarov J, et al. The intracellular sRNA transcriptome of Listeria monocytogenes during growth in macrophages. Nucleic Acids Res. 2011;39(10):4235–48. doi: 10.1093/nar/gkr033 21278422; PubMed Central PMCID: PMC3105390.

19. Ortega AD, Gonzalo-Asensio J, Garcia-del Portillo F. Dynamics of Salmonella small RNA expression in non-growing bacteria located inside eukaryotic cells. RNA Biol. 2012;9(4):469–88. doi: 10.4161/rna.19317 22336761.

20. Pichon C, du Merle L, Caliot ME, Trieu-Cuot P, Le Bouguenec C. An in silico model for identification of small RNAs in whole bacterial genomes: characterization of antisense RNAs in pathogenic Escherichia coli and Streptococcus agalactiae strains. Nucleic Acids Res. 2012;40(7):2846–61. doi: 10.1093/nar/gkr1141 22139924; PubMed Central PMCID: PMC3326304.

21. Liu Z, Trevino J, Ramirez-Pena E, Sumby P. The small regulatory RNA FasX controls pilus expression and adherence in the human bacterial pathogen group A Streptococcus. Mol Microbiol. 2012;86(1):140–54. doi: 10.1111/j.1365-2958.2012.08178.x 22882718; PubMed Central PMCID: PMC3456998.

22. Rentschler AE, Lovrich SD, Fitton R, Enos-Berlage J, Schwan WR. OmpR regulation of the uropathogenic Escherichia coli fimB gene in an acidic/high osmolality environment. Microbiology. 2013;159(Pt 2):316–27. doi: 10.1099/mic.0.059386-0 23175504.

23. Simonsen KT, Nielsen G, Bjerrum JV, Kruse T, Kallipolitis BH, Moller-Jensen J. A role for the RNA chaperone Hfq in controlling adherent-invasive Escherichia coli colonization and virulence. PLoS One. 2011;6(1):e16387. doi: 10.1371/journal.pone.0016387 21298102; PubMed Central PMCID: PMC3027648.

24. Bellows LE, Koestler BJ, Karaba SM, Waters CM, Lathem WW. Hfq-dependent, co-ordinate control of cyclic diguanylate synthesis and catabolism in the plague pathogen Yersinia pestis. Mol Microbiol. 2012;86(3):661–74. doi: 10.1111/mmi.12011 22924957; PubMed Central PMCID: PMC3480973.

25. Wilms I, Moller P, Stock AM, Gurski R, Lai EM, Narberhaus F. Hfq influences multiple transport systems and virulence in the plant pathogen Agrobacterium tumefaciens. J Bacteriol. 2012;194(19):5209–17. doi: 10.1128/JB.00510-12 22821981; PubMed Central PMCID: PMC3457239.

26. Zeng Q, McNally RR, Sundin GW. Global small RNA chaperone Hfq and regulatory small RNAs are important virulence regulators in Erwinia amylovora. J Bacteriol. 2013;195(8):1706–17. doi: 10.1128/JB.02056-12 23378513; PubMed Central PMCID: PMCPMC3624556.

27. De Lay N, Gottesman S. A complex network of small non-coding RNAs regulate motility in Escherichia coli. Mol Microbiol. 2012;86(3):524–38. doi: 10.1111/j.1365-2958.2012.08209.x 22925049.

28. Roscetto E, Angrisano T, Costa V, Casalino M, Forstner KU, Sharma CM, et al. Functional characterization of the RNA chaperone Hfq in the opportunistic human pathogen Stenotrophomonas maltophilia. J Bacteriol. 2012;194(21):5864–74. doi: 10.1128/JB.00746-12 22923593; PubMed Central PMCID: PMC3486118.

29. Gong H, Vu GP, Bai Y, Chan E, Wu R, Yang E, et al. A Salmonella small non-coding RNA facilitates bacterial invasion and intracellular replication by modulating the expression of virulence factors. PLoS pathogens. 2011;7(9):e1002120. doi: 10.1371/journal.ppat.1002120 21949647; PubMed Central PMCID: PMC3174252.

30. Postic G, Dubail I, Frapy E, Dupuis M, Dieppedale J, Charbit A, et al. Identification of a novel small RNA modulating Francisella tularensis pathogenicity. PLoS One. 2012;7(7):e41999. doi: 10.1371/journal.pone.0041999 22848684; PubMed Central PMCID: PMC3405028.

31. Yan Y, Su S, Meng X, Ji X, Qu Y, Liu Z, et al. Determination of sRNA Expressions by RNA-seq in Yersinia pestis Grown In Vitro and during Infection. PLoS One. 2013;8(9):e74495. doi: 10.1371/journal.pone.0074495 24040259.

32. Uzzau S, Figueroa-Bossi N, Rubino S, Bossi L. Epitope tagging of chromosomal genes in Salmonella. Proc Natl Acad Sci U S A. 2001;98(26):15264–9. doi: 10.1073/pnas.261348198 11742086; PubMed Central PMCID: PMC65018.

33. Mulvey MA, Schilling JD, Hultgren SJ. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun. 2001;69(7):4572–9. doi: 10.1128/IAI.69.7.4572-4579.2001 11402001; PubMed Central PMCID: PMC98534.

34. Berry RE, Klumpp DJ, Schaeffer AJ. Urothelial cultures support intracellular bacterial community formation by uropathogenic Escherichia coli. Infect Immun. 2009;77(7):2762–72. doi: 10.1128/IAI.00323-09 19451249; PubMed Central PMCID: PMC2708588.

35. Kulesus RR, Diaz-Perez K, Slechta ES, Eto DS, Mulvey MA. Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli. Infect Immun. 2008;76(7):3019–26. doi: 10.1128/IAI.00022-08 18458066; PubMed Central PMCID: PMC2446724.

36. Johansen J, Rasmussen AA, Overgaard M, Valentin-Hansen P. Conserved small non-coding RNAs that belong to the sigmaE regulon: role in down-regulation of outer membrane proteins. Journal of molecular biology. 2006;364(1):1–8. doi: 10.1016/j.jmb.2006.09.004 17007876.

37. Papenfort K, Pfeiffer V, Mika F, Lucchini S, Hinton JC, Vogel J. SigmaE-dependent small RNAs of Salmonella respond to membrane stress by accelerating global omp mRNA decay. Mol Microbiol. 2006;62(6):1674–88. 17427289; PubMed Central PMCID: PMC1804206.

38. Udekwu KI, Wagner EG. Sigma E controls biogenesis of the antisense RNA MicA. Nucleic Acids Res. 2007;35(4):1279–88. doi: 10.1093/nar/gkl1154 17267407; PubMed Central PMCID: PMC1851643.

39. Livny J, Teonadi H, Livny M, Waldor MK. High-throughput, kingdom-wide prediction and annotation of bacterial non-coding RNAs. PLoS One. 2008;3(9):e3197. doi: 10.1371/journal.pone.0003197 18787707; PubMed Central PMCID: PMC2527527.

40. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Research. 2003;31(13):3406–15. doi: 10.1093/nar/gkg595 12824337

41. Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, et al. Comparative genomics boosts target prediction for bacterial small RNAs. Proc Natl Acad Sci U S A. 2013;110(37):E3487–96. doi: 10.1073/pnas.1303248110 23980183; PubMed Central PMCID: PMC3773804.

42. Klemm P, Roos V, Ulett GC, Svanborg C, Schembri MA. Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: the taming of a pathogen. Infect Immun. 2006;74(1):781–5. doi: 10.1128/IAI.74.1.781-785.2006 16369040; PubMed Central PMCID: PMCPMC1346676.

43. Lloyd AL, Henderson TA, Vigil PD, Mobley HL. Genomic islands of uropathogenic Escherichia coli contribute to virulence. J Bacteriol. 2009;191(11):3469–81. doi: 10.1128/JB.01717-08 19329634; PubMed Central PMCID: PMC2681901.

44. Nilsson P, Uhlin BE. Differential decay of a polycistronic Escherichia coli transcript is initiated by RNaseE-dependent endonucleolytic processing. Mol Microbiol. 1991;5(7):1791–9. 1943710.

45. Altuvia S, Zhang A, Argaman L, Tiwari A, Storz G. The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding. The EMBO journal. 1998;17(20):6069–75. doi: 10.1093/emboj/17.20.6069 9774350; PubMed Central PMCID: PMC1170933.

46. Vendittelli F, Alain J, Nouaille Y, Brosset A, Tabaste JL. A case of lipomeningocele reported with fluoxetine (and alprazolam, vitamins B1 and B6, heptaminol) prescribed during pregnancy. European journal of obstetrics, gynecology, and reproductive biology. 1995;58(1):85–6. 7758651.

47. Nou X, Braaten B, Kaltenbach L, Low DA. Differential binding of Lrp to two sets of pap DNA binding sites mediated by Pap I regulates Pap phase variation in Escherichia coli. The EMBO journal. 1995;14(23):5785–97. 8846772; PubMed Central PMCID: PMC394697.

48. Kawamura T, Vartanian AS, Zhou H, Dahlquist FW. The design involved in PapI and Lrp regulation of the pap operon. Journal of molecular biology. 2011;409(3):311–32. doi: 10.1016/j.jmb.2011.01.058 21338611.

49. Storz G, Vogel J, Wassarman KM. Regulation by small RNAs in bacteria: expanding frontiers. Molecular cell. 2011;43(6):880–91. doi: 10.1016/j.molcel.2011.08.022 21925377; PubMed Central PMCID: PMC3176440.

50. Pfeiffer V, Papenfort K, Lucchini S, Hinton JC, Vogel J. Coding sequence targeting by MicC RNA reveals bacterial mRNA silencing downstream of translational initiation. Nature structural & molecular biology. 2009;16(8):840–6. doi: 10.1038/nsmb.1631 19620966.

51. Urban JH, Vogel J. Translational control and target recognition by Escherichia coli small RNAs in vivo. Nucleic Acids Res. 2007;35(3):1018–37. doi: 10.1093/nar/gkl1040 17264113; PubMed Central PMCID: PMC1807950.

52. Hebrard M, Kroger C, Srikumar S, Colgan A, Handler K, Hinton JC. sRNAs and the virulence of Salmonella enterica serovar Typhimurium. RNA Biol. 2012;9(4):437–45. doi: 10.4161/rna.20480 22546935; PubMed Central PMCID: PMC3384567.

53. Ortega AD, Quereda JJ, Pucciarelli MG, Garcia-del Portillo F. Non-coding RNA regulation in pathogenic bacteria located inside eukaryotic cells. Frontiers in cellular and infection microbiology. 2014;4:162. doi: 10.3389/fcimb.2014.00162 25429360; PubMed Central PMCID: PMC4228915.

54. Vogel J, Luisi BF. Hfq and its constellation of RNA. Nature reviews Microbiology. 2011;9(8):578–89. doi: 10.1038/nrmicro2615 21760622.

55. Waters LS, Storz G. Regulatory RNAs in bacteria. Cell. 2009;136(4):615–28. doi: 10.1016/j.cell.2009.01.043 19239884; PubMed Central PMCID: PMC3132550.

56. Soper T, Mandin P, Majdalani N, Gottesman S, Woodson SA. Positive regulation by small RNAs and the role of Hfq. Proc Natl Acad Sci U S A. 2010;107(21):9602–7. doi: 10.1073/pnas.1004435107 20457943; PubMed Central PMCID: PMC2906882.

57. Schwartz DJ, Chen SL, Hultgren SJ, Seed PC. Population dynamics and niche distribution of uropathogenic Escherichia coli during acute and chronic urinary tract infection. Infect Immun. 2011;79(10):4250–9. doi: 10.1128/IAI.05339-11 21807904; PubMed Central PMCID: PMC3187256.

58. Nicholson TF, Watts KM, Hunstad DA. OmpA of uropathogenic Escherichia coli promotes postinvasion pathogenesis of cystitis. Infect Immun. 2009;77(12):5245–51. doi: 10.1128/IAI.00670-09 19797074; PubMed Central PMCID: PMC2786482.

59. McCullen CA, Benhammou JN, Majdalani N, Gottesman S. Mechanism of positive regulation by DsrA and RprA small noncoding RNAs: pairing increases translation and protects rpoS mRNA from degradation. J Bacteriol. 2010;192(21):5559–71. doi: 10.1128/JB.00464-10 20802038; PubMed Central PMCID: PMC2953674.

60. Hryckowian AJ, Welch RA. RpoS contributes to phagocyte oxidase-mediated stress resistance during urinary tract infection by Escherichia coli CFT073. MBio. 2013;4(1):e00023–13. doi: 10.1128/mBio.00023-13 23404396; PubMed Central PMCID: PMCPMC3573659.

61. Jin Y, Watt RM, Danchin A, Huang JD. Small noncoding RNA GcvB is a novel regulator of acid resistance in Escherichia coli. BMC genomics. 2009;10:165. doi: 10.1186/1471-2164-10-165 19379489; PubMed Central PMCID: PMC2676305.

62. Urbanowski ML, Stauffer LT, Stauffer GV. The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli. Mol Microbiol. 2000;37(4):856–68. 10972807.

63. Jorgensen MG, Nielsen JS, Boysen A, Franch T, Moller-Jensen J, Valentin-Hansen P. Small regulatory RNAs control the multi-cellular adhesive lifestyle of Escherichia coli. Mol Microbiol. 2012;84(1):36–50. doi: 10.1111/j.1365-2958.2012.07976.x 22250746.

64. Coornaert A, Chiaruttini C, Springer M, Guillier M. Post-transcriptional control of the Escherichia coli PhoQ-PhoP two-component system by multiple sRNAs involves a novel pairing region of GcvB. PLoS Genet. 2013;9(1):e1003156. doi: 10.1371/journal.pgen.1003156 23300478; PubMed Central PMCID: PMCPMC3536696.

65. Modi SR, Camacho DM, Kohanski MA, Walker GC, Collins JJ. Functional characterization of bacterial sRNAs using a network biology approach. Proc Natl Acad Sci U S A. 2011;108(37):15522–7. doi: 10.1073/pnas.1104318108 21876160; PubMed Central PMCID: PMC3174649.

66. Graham MR, Virtaneva K, Porcella SF, Gardner DJ, Long RD, Welty DM, et al. Analysis of the transcriptome of group A Streptococcus in mouse soft tissue infection. The American journal of pathology. 2006;169(3):927–42. doi: 10.2353/ajpath.2006.060112 16936267; PubMed Central PMCID: PMC1698835.

67. Ventre I, Goodman AL, Vallet-Gely I, Vasseur P, Soscia C, Molin S, et al. Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes. Proc Natl Acad Sci U S A. 2006;103(1):171–6. doi: 10.1073/pnas.0507407103 16373506; PubMed Central PMCID: PMC1324988.

68. Chao Y, Papenfort K, Reinhardt R, Sharma CM, Vogel J. An atlas of Hfq-bound transcripts reveals 3' UTRs as a genomic reservoir of regulatory small RNAs. The EMBO journal. 2012;31(20):4005–19. doi: 10.1038/emboj.2012.229 22922465; PubMed Central PMCID: PMC3474919.

69. Wurpel DJ, Beatson SA, Totsika M, Petty NK, Schembri MA. Chaperone-usher fimbriae of Escherichia coli. PLoS One. 2013;8(1):e52835. doi: 10.1371/journal.pone.0052835 23382825; PubMed Central PMCID: PMC3559732.

70. Snyder JA, Haugen BJ, Buckles EL, Lockatell CV, Johnson DE, Donnenberg MS, et al. Transcriptome of uropathogenic Escherichia coli during urinary tract infection. Infect Immun. 2004;72(11):6373–81. doi: 10.1128/IAI.72.11.6373-6381.2004 15501767; PubMed Central PMCID: PMC523057.

71. Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, et al. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science. 1998;282(5393):1494–7. 9822381.

72. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. The EMBO journal. 2000;19(12):2803–12. doi: 10.1093/emboj/19.12.2803 10856226; PubMed Central PMCID: PMC203355.

73. Holden NJ, Totsika M, Mahler E, Roe AJ, Catherwood K, Lindner K, et al. Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli. Microbiology. 2006;152(Pt 4):1143–53. doi: 10.1099/mic.0.28677-0 16549677.

74. Andersson M, Uhlin BE, Fallman E. The biomechanical properties of E. coli pili for urinary tract attachment reflect the host environment. Biophys J. 2007;93(9):3008–14. doi: 10.1529/biophysj.107.110643 17675342; PubMed Central PMCID: PMC2025661.

75. Buckles EL, Luterbach CL, Wang X, Lockatell CV, Johnson DE, Mobley HL, et al. Signature-tagged mutagenesis and co-infection studies demonstrate the importance of P fimbriae in a murine model of urinary tract infection. Pathogens and disease. 2015;73(4). doi: 10.1093/femspd/ftv014 25673667.

76. Lund B, Lindberg F, Marklund BI, Normark S. The PapG protein is the alpha-D-galactopyranosyl-(1——4)-beta-D-galactopyranose-binding adhesin of uropathogenic Escherichia coli. Proc Natl Acad Sci U S A. 1987;84(16):5898–902. 2886993; PubMed Central PMCID: PMC298970.

77. Hedlund M, Svensson M, Nilsson A, Duan RD, Svanborg C. Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli. The Journal of experimental medicine. 1996;183(3):1037–44. 8642245; PubMed Central PMCID: PMC2192311.

78. Frendeus B, Wachtler C, Hedlund M, Fischer H, Samuelsson P, Svensson M, et al. Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation. Mol Microbiol. 2001;40(1):37–51. 11298274.

79. Rice JC, Peng T, Spence JS, Wang HQ, Goldblum RM, Corthesy B, et al. Pyelonephritic Escherichia coli expressing P fimbriae decrease immune response of the mouse kidney. Journal of the American Society of Nephrology: JASN. 2005;16(12):3583–91. doi: 10.1681/ASN.2005030243 16236807.

80. Holden NJ, Gally DL. Switches, cross-talk and memory in Escherichia coli adherence. Journal of medical microbiology. 2004;53(Pt 7):585–93. 15184527.

81. Gunther NWt, Lockatell V, Johnson DE, Mobley HL. In vivo dynamics of type 1 fimbria regulation in uropathogenic Escherichia coli during experimental urinary tract infection. Infect Immun. 2001;69(5):2838–46. doi: 10.1128/IAI.69.5.2838-2846.2001 11292696; PubMed Central PMCID: PMC98232.

82. Graveline R, Mourez M, Hancock MA, Martin C, Boisclair S, Harel J. Lrp-DNA complex stability determines the level of ON cells in type P fimbriae phase variation. Mol Microbiol. 2011;81(5):1286–99. doi: 10.1111/j.1365-2958.2011.07761.x 21752106.

83. Willins DA, Ryan CW, Platko JV, Calvo JM. Characterization of Lrp, and Escherichia coli regulatory protein that mediates a global response to leucine. J Biol Chem. 1991;266(17):10768–74. 2040596.

84. Danger JL, Cao TN, Cao TH, Sarkar P, Trevino J, Pflughoeft KJ, et al. The small regulatory RNA FasX enhances group A Streptococcus virulence and inhibits pilus expression via serotype-specific targets. Mol Microbiol. 2015;96(2):249–62. doi: 10.1111/mmi.12935 25586884; PubMed Central PMCID: PMC4390479.

85. Karavolos MH, Winzer K, Williams P, Khan CM. Pathogen espionage: multiple bacterial adrenergic sensors eavesdrop on host communication systems. Mol Microbiol. 2013;87(3):455–65. doi: 10.1111/mmi.12110 23231070.

86. Datsenko KA, Wanner BL. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A. 2000;97(12):6640–5. doi: 10.1073/pnas.120163297 10829079; PubMed Central PMCID: PMC18686.

87. Boysen A, Moller-Jensen J, Kallipolitis B, Valentin-Hansen P, Overgaard M. Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli. J Biol Chem. 2010;285(14):10690–702. doi: 10.1074/jbc.M109.089755 20075074; PubMed Central PMCID: PMC2856277.

88. Overgaard M, Johansen J, Moller-Jensen J, Valentin-Hansen P. Switching off small RNA regulation with trap-mRNA. Mol Microbiol. 2009;73(5):790–800. doi: 10.1111/j.1365-2958.2009.06807.x 19682266.

89. Franch T, Gultyaev AP, Gerdes K. Programmed cell death by hok/sok of plasmid R1: processing at the hok mRNA 3'-end triggers structural rearrangements that allow translation and antisense RNA binding. Journal of molecular biology. 1997;273(1):38–51. doi: 10.1006/jmbi.1997.1294 9367744.

90. Krogfelt KA, Bergmans H, Klemm P. Direct evidence that the FimH protein is the mannose-specific adhesin of Escherichia coli type 1 fimbriae. Infect Immun. 1990;58(6):1995–8. 1971261; PubMed Central PMCID: PMC258756.

91. Smith C, Heyne S, Richter AS, Will S, Backofen R. Freiburg RNA Tools: a web server integrating INTARNA, EXPARNA and LOCARNA. Nucleic Acids Res. 2010;38(Web Server issue):W373–7. doi: 10.1093/nar/gkq316 20444875; PubMed Central PMCID: PMC2896085.