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During their life cycle, enteropathogenic Yersiniae are exposed to different environments inside and outside host organisms. Therefore, they have to adapt their gene expression depending on the condition in order to persist.

The overall goal of this study was to investigate the influence of environmental conditions on the transcriptional landscape of enteropathogenic Yersinia species. To address this question, RNA-seq should be applied. This approach allows the investigation of global changes in gene expression in response to environmental signals as well as the role of non-coding RNAs (ncRNAs) for Yersinia virulence.

For Y. pseudotuberculosis this approach has been used in a previous study (Nuss et al., 2015). This has gained a deep insight into the gene expression profile and has lead to the discovery of new ncRNAs. Here, tissue-dual RNA-sequencing of Y. pseudotuberculosis in mouse Peyer’s Patches was applied to investigate changes between in vitro and in vivo conditions. One aim of this study was the analysis of a target set of genes and ncRNAs that were found to be upregulated in vivo. These targets should be investigated further to identify their role during the infection process. For this purpose, deletion mutants should be created and analyzed.

Another aim of this study was to compare the transcription profile of two Y. enterocolitica serotypes in response to temperature and nutrient availability. Most cases of Yersiniosis in the EU and the USA are caused the bioserotype 4/O:3 (YeO:3) (Bottone, 1999; Bucher et al., 2008; Rosner et al., 2010). However, the bioserotype 1B/O:8 (YeO:8), highly mouse virulent and commonly used in laboratory experiments, is responsible for only 1% of the Yersiniosis cases in Germany (Rosner et al., 2010). Previous studies have shown that both, YeO:3 and YeO:8 are able to colonize mice. But while the YeO:3 infected mice stay clinically healthy, the ones infected with YeO:8 show severe pathological changes (Schaake et al., 2014). On the other hand, YeO:3 was shown to be able to colonize pigs, in contrast to YeO:8 (Schaake et al., 2014). This work aims to investigate the differences of both serotypes on the transcriptional level to gain insights into the mechanisms underlying the different colonization phenotypes. To address this, RNA-seq of Y. enterocolitica at different in vitro conditions should be established. The results should be used to analyze changes in the transcriptional profile on a global level. Gene expression and the presence of ncRNAs should be investigated and a global map of transcriptional start sites for Y. enterocolitica should be created.

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31 2.9 References

Achtman, M., Zurth, K., Morelli, G., Torrea, G., Guiyoule, A., and Carniel, E. (1999). Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc. Natl.

Acad. Sci. U.S.A. 96, 14043–14048.

Ackers, M.L., Schoenfeld, S., Markman, J., Smith, M.G., Nicholson, M.A., DeWitt, W., Cameron, D.N., Griffin, P.M., and Slutsker, L. (2000). An outbreak of Yersinia enterocolitica O:8 infections associated with pasteurized milk. J. Infect. Dis. 181, 1834–1837.

Adamkiewicz, T.V., Berkovitch, M., Krishnan, C., Polsinelli, C., Kermack, D., and Olivieri, N.F.

(1998). Infection due to Yersinia enterocolitica in a series of patients with beta-thalassemia: incidence and predisposing factors. Clin. Infect. Dis. 27, 1362–1366.

Albrecht, M., Sharma, C.M., Dittrich, M.T., Müller, T., Reinhardt, R., Vogel, J., and Rudel, T.

(2011). The transcriptional landscape of Chlamydia pneumoniae. Genome Biol. 12, R98.

von Altrock, A., Louis, A.L., Rösler, U., Alter, T., Beyerbach, M., Kreienbrocks, L., and Waldmann, K.-H. (2006). [The bacteriological and serological prevalence of Campylobacter spp. and Yersinia enterocolitica in fattening pig herds in Lower Saxony]. Berl. Munch. Tierarztl. Wochenschr.

119, 391–399.

Arnold, W.K., Savage, C.R., Brissette, C.A., Seshu, J., Livny, J., and Stevenson, B. (2016). RNA-Seq of Borrelia burgdorferi in Multiple Phases of Growth Reveals Insights into the Dynamics of Gene Expression, Transcriptome Architecture, and Noncoding RNAs. PLoS ONE 11, e0164165.

Autenrieth, I.B., Kempf, V., Sprinz, T., Preger, S., and Schnell, A. (1996). Defense mechanisms in Peyer’s patches and mesenteric lymph nodes against Yersinia enterocolitica involve integrins and cytokines. Infect. Immun. 64, 1357–1368.

Avican, K., Fahlgren, A., Huss, M., Heroven, A.K., Beckstette, M., Dersch, P., and Fällman, M.

(2015). Reprogramming of Yersinia from virulent to persistent mode revealed by complex in vivo RNA-seq analysis. PLoS Pathog. 11, e1004600.

Balbontín, R., Villagra, N., Pardos de la Gándara, M., Mora, G., Figueroa-Bossi, N., and Bossi, L.

(2016). Expression of IroN, the salmochelin siderophore receptor, requires mRNA activation by RyhB small RNA homologues. Mol. Microbiol. 100, 139–155.

Bancerz-Kisiel, A., and Szweda, W. (2015). Yersiniosis - a zoonotic foodborne disease of relevance to public health. Ann Agric Environ Med 22, 397–402.

Batzilla, J., Antonenka, U., Höper, D., Heesemann, J., and Rakin, A. (2011). Yersinia enterocolitica palearctica serobiotype O:3/4--a successful group of emerging zoonotic pathogens. BMC Genomics 12, 348.

Bengoechea, J.A., Díaz, R., and Moriyón, I. (1996). Outer membrane differences between pathogenic and environmental Yersinia enterocolitica biogroups probed with hydrophobic permeants and polycationic peptides. Infect. Immun. 64, 4891–4899.

2 Introduction

32

Bengoechea, J.A., Najdenski, H., and Skurnik, M. (2004). Lipopolysaccharide O antigen status of Yersinia enterocolitica O:8 is essential for virulence and absence of O antigen affects the expression of other Yersinia virulence factors. Mol. Microbiol. 52, 451–469.

Białas, N., Kasperkiewicz, K., Radziejewska-Lebrecht, J., and Skurnik, M. (2012). Bacterial cell surface structures in Yersinia enterocolitica. Arch. Immunol. Ther. Exp. (Warsz.) 60, 199–209.

Biedzka-Sarek, M., Venho, R., and Skurnik, M. (2005). Role of YadA, Ail, and Lipopolysaccharide in Serum Resistance of Yersinia enterocolitica Serotype O:3. Infect. Immun. 73, 2232–2244.

Biedzka-Sarek, M., Salmenlinna, S., Gruber, M., Lupas, A.N., Meri, S., and Skurnik, M. (2008).

Functional mapping of YadA- and Ail-mediated binding of human factor H to Yersinia enterocolitica serotype O:3. Infect. Immun. 76, 5016–5027.

Bliska, J.B., and Falkow, S. (1992). Bacterial resistance to complement killing mediated by the Ail protein of Yersinia enterocolitica. Proc. Natl. Acad. Sci. U.S.A. 89, 3561–3565.

Bliska, J.B., Copass, M.C., and Falkow, S. (1993).The Yersinia pseudotuberculosis adhesin YadA mediates intimate bacterial attachment to and entry into HEp-2 cells. Infect. Immun.61,3914–3921.

Boardman, B.K., and Satchell, K.J.F. (2004). Vibrio cholerae strains with mutations in an atypical type I secretion system accumulate RTX toxin intracellularly. J. Bacteriol. 186, 8137–8143.

Bobrov, A.G., Kirillina, O., Fetherston, J.D., Miller, M.C., Burlison, J.A., and Perry, R.D. (2014).

The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice. Mol. Microbiol. 93, 759–775.

Bottone, E.J. (1997). Yersinia enterocolitica: the charisma continues. Clin. Microbiol.Rev.10,257–276.

Bottone, E.J. (1999). Yersinia enterocolitica: overview and epidemiologic correlates. Microbes Infect.

1, 323–333.

Bradley, R.M., Gander, R.M., Patel, S.K., and Kaplan, H.S. (1997). Inhibitory effect of 0 degree C storage on the proliferation of Yersinia enterocolitica in donated blood. Transfusion 37, 691–695.

Brinkkötter, A., Klöss, H., Alpert, C., and Lengeler, J.W. (2000). Pathways for the utilization of N-acetyl-galactosamine and galactosamine in Escherichia coli. Mol. Microbiol. 37, 125–135.

Brubaker, R.R. (1991). Factors promoting acute and chronic diseases caused by yersiniae. Clin.

Microbiol. Rev. 4, 309–324.

Bucher, M., Meyer, C., Grötzbach, B., Wacheck, S., Stolle, A., and Fredriksson-Ahomaa, M.

(2008). Epidemiological data on pathogenic Yersinia enterocolitica in Southern Germany during 2000-2006. Foodborne Pathog. Dis. 5, 273–280.

Butcher, J., and Stintzi, A. (2013). The transcriptional landscape of Campylobacter jejuni under iron replete and iron limited growth conditions. PLoS ONE 8, e79475.

Butler, T. (2013). Plague gives surprises in the first decade of the 21st century in the United States and worldwide. Am. J. Trop. Med. Hyg. 89, 788–793.

2 Introduction

33

Calderón, I.L., Morales, E.H., Collao, B., Calderón, P.F., Chahuán, C.A., Acuña, L.G., Gil, F., and Saavedra, C.P. (2014). Role of Salmonella Typhimurium small RNAs RyhB-1 and RyhB-2 in the oxidative stress response. Res. Microbiol. 165, 30–40.

Carniel, E. (2001). The Yersinia high-pathogenicity island: an iron-uptake island. Microbes Infect. 3, 561–569.

Chain, P.S.G., Carniel, E., Larimer, F.W., Lamerdin, J., Stoutland, P.O., Regala, W.M., Georgescu, A.M., Vergez, L.M., Land, M.L., Motin, V.L., et al. (2004). Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis. Proc. Natl.

Acad. Sci. U.S.A. 101, 13826–13831.

Chakraborty, A., Komatsu, K., Roberts, M., Collins, J., Beggs, J., Turabelidze, G., Safranek, T., Maillard, J.-M., Bell, L.J., Young, D., et al. (2015). The descriptive epidemiology of yersiniosis: a multistate study, 2005-2011. Public Health Rep 130, 269–277.

Chester, B., Stotzky, G., Bottone, E.J., Malowany, M.S., and Allerhand, J. (1977). Yersinia enterocolitica: biochemical, serological, and gas-liquid chromatographic characterization of rhamnose-, raffinose-, melibiose-, and citrate-utilizing strains. J. Clin. Microbiol. 6, 461–468.

Cornelis, G.R. (1998). The Yersinia deadly kiss. J. Bacteriol. 180, 5495–5504.

Cornelis, G.R. (2002). Yersinia type III secretion: send in the effectors. J. Cell Biol. 158, 401–408.

Cornelis, G.R., Boland, A., Boyd, A.P., Geuijen, C., Iriarte, M., Neyt, C., Sory, M.P., and Stainier, I. (1998).The virulence plasmid of Yersinia, an antihost genome.Microbiol.Mol.Biol.Rev.62,1315–1352.

Cunneen, M.M., Pacinelli, E., Song, W.C., and Reeves, P.R. (2011). Genetic analysis of the O-antigen gene clusters of Yersinia pseudotuberculosis O:6 and O:7. Glycobiology 21, 1140–1146.

Dadzie, I., Xu, S., Ni, B., Zhang, X., Zhang, H., Sheng, X., Xu, H., and Huang, X. (2013).

Identification and characterization of a cis-encoded antisense RNA associated with the replication process of Salmonella enterica serovar Typhi. PLoS ONE 8, e61308.

Deacon, A.G., Hay, A., and Duncan, J. (2003). Septicemia due to Yersinia pseudotuberculosis--a case report. Clin. Microbiol. Infect. 9, 1118–1119.

Dersch, P., Khan, M.A., Mühlen, S., and Görke, B. (2017). Roles of Regulatory RNAs for Antibiotic Resistance in Bacteria and Their Potential Value as Novel Drug Targets. Front Microbiol 8, 803.

Dewoody, R.S., Merritt, P.M., and Marketon, M.M. (2013). Regulation of the Yersinia type III secretion system: traffic control. Front Cell Infect Microbiol 3, 4.

Dötsch, A., Eckweiler, D., Schniederjans, M., Zimmermann, A., Jensen, V., Scharfe, M., Geffers, R., and Häussler, S. (2012). The Pseudomonas aeruginosa transcriptome in planktonic cultures and static biofilms using RNA sequencing. PLoS ONE 7, e31092.

Duan, R., Liang, J., Shi, G., Cui, Z., Hai, R., Wang, P., Xiao, Y., Li, K., Qiu, H., Gu, W., et al.

(2014). Homology analysis of pathogenic Yersinia species Yersinia enterocolitica, Yersinia

2 Introduction

34

pseudotuberculosis, and Yersinia pestis based on multilocus sequence typing. J. Clin. Microbiol. 52, 20–29.

Durand, E.A., Maldonado-Arocho, F.J., Castillo, C., Walsh, R.L., and Mecsas, J. (2010). The presence of professional phagocytes dictates the number of host cells targeted for Yop translocation during infection. Cell. Microbiol. 12, 1064–1082.

European Food Safety Authority (EFSA) (2015). The European Union summary report on trends and sources of zoonoses , trends and sources of zoonoses , zoonotic agents and food-borne outbreaks in 2015.

Eitel, J., and Dersch, P. (2002). The YadA protein of Yersinia pseudotuberculosis mediates high-efficiency uptake into human cells under environmental conditions in which invasin is repressed.

Infect. Immun. 70, 4880–4891.

Erridge, C., Bennett-Guerrero, E., and Poxton, I.R. (2002). Structure and function of lipopolysaccharides. Microbes Infect. 4, 837–851.

Falcão, J.P., Falcão, D.P., Pitondo-Silva, A., Malaspina, A.C., and Brocchi, M. (2006). Molecular typing and virulence markers of Yersinia enterocolitica strains from human, animal and food origins isolated between 1968 and 2000 in Brazil. J. Med. Microbiol. 55, 1539–1548.

Foley, J.A., and Mathews, J.A. (1984). Reactive arthritis due to Yersinia enterocolitica. Clin.

Rheumatol. 3, 385–387.

Fonseca, D.M. da, Hand, T.W., Han, S.-J., Gerner, M.Y., Glatman Zaretsky, A., Byrd, A.L., Harrison, O.J., Ortiz, A.M., Quinones, M., Trinchieri, G., et al. (2015). Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity. Cell 163, 354–366.

Forman, S., Paulley, J.T., Fetherston, J.D., Cheng, Y.-Q., and Perry, R.D. (2010). Yersinia ironomics: comparison of iron transporters among Yersinia pestis biotypes and its nearest neighbor, Yersinia pseudotuberculosis. Biometals 23, 275–294.

Foultier, B., Troisfontaines, P., Müller, S., Opperdoes, F.R., and Cornelis, G.R. (2002).

Characterization of the ysa pathogenicity locus in the chromosome of Yersinia enterocolitica and phylogeny analysis of type III secretion systems. J. Mol. Evol. 55, 37–51.

Foultier, B., Troisfontaines, P., Vertommen, D., Marenne, M.-N., Rider, M., Parsot, C., and Cornelis, G.R. (2003). Identification of substrates and chaperone from the Yersinia enterocolitica 1B Ysa type III secretion system. Infect. Immun. 71, 242–253.

Fredriksson-Ahomaa, M., Stolle, A., Siitonen, A., and Korkeala, H. (2006). Sporadic human Yersinia enterocolitica infections caused by bioserotype 4/O  : 3 originate mainly from pigs. J. Med.

Microbiol. 55, 747–749.

Fröhlich, K.S., Papenfort, K., Berger, A.A., and Vogel, J. (2012). A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD. Nucleic Acids Res. 40, 3623–3640.

2 Introduction

35

Fukushima, H., Gomyoda, M., Shiozawa, K., Kaneko, S., and Tsubokura, M. (1988). Yersinia pseudotuberculosis infection contracted through water contaminated by a wild animal. J. Clin.

Microbiol. 26, 584–585.

Georg, J., and Hess, W.R. (2011). cis-antisense RNA, another level of gene regulation in bacteria.

Microbiol. Mol. Biol. Rev. 75, 286–300.

Giangrossi, M., Prosseda, G., Tran, C.N., Brandi, A., Colonna, B., and Falconi, M. (2010). A novel antisense RNA regulates at transcriptional level the virulence gene icsA of Shigella flexneri. Nucleic Acids Res. 38, 3362–3375.

Gómez-Lozano, M., Marvig, R.L., Molin, S., and Long, K.S. (2012). Genome-wide identification of novel small RNAs in Pseudomonas aeruginosa. Environ. Microbiol. 14, 2006–2016.

Gong, H., Vu, G.-P., Bai, Y., Chan, E., Wu, R., Yang, E., Liu, F., and Lu, S. (2011). A Salmonella small non-coding RNA facilitates bacterial invasion and intracellular replication by modulating the expression of virulence factors. PLoS Pathog. 7, e1002120.

Gottesman, S., McCullen, C.A., Guillier, M., Vanderpool, C.K., Majdalani, N., Benhammou, J., Thompson, K.M., FitzGerald, P.C., Sowa, N.A., and FitzGerald, D.J. (2006). Small RNA regulators and the bacterial response to stress. Cold Spring Harb. Symp. Quant. Biol. 71, 1–11.

Grützkau, A., Hanski, C., Hahn, H., and Riecken, E.O. (1990). Involvement of M cells in the bacterial invasion of Peyer’s patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. Gut 31, 1011–1015.

Håkansson, S., Bergman, T., Vanooteghem, J.C., Cornelis, G., and Wolf-Watz, H. (1993). YopB and YopD constitute a novel class of Yersinia Yop proteins. Infect. Immun. 61, 71–80.

Haller, J.C., Carlson, S., Pederson, K.J., and Pierson, D.E. (2000). A chromosomally encoded type III secretion pathway in Yersinia enterocolitica is important in virulence. Mol. Microbiol. 36, 1436–1446.

Hamburger, Z.A., Brown, M.S., Isberg, R.R., and Bjorkman, P.J. (1999). Crystal structure of invasin: a bacterial integrin-binding protein. Science 286, 291–295.

Hammer, B.K., and Bassler, B.L. (2007). Regulatory small RNAs circumvent the conventional quorum sensing pathway in pandemic Vibrio cholerae. Proc Natl. Acad. Sci. U.S.A. 104,11145–11149.

Hansen-Wester, I., and Hensel, M. (2001). Salmonella pathogenicity islands encoding type III secretion systems. Microbes Infect. 3, 549–559.

Hartung, M., and Gerigk, K. (1991). Yersinia in effluents from the food-processing industry. Rev. - Off. Int. Epizoot. 10, 799–811.

Heesemann, J., Hantke, K., Vocke, T., Saken, E., Rakin, A., Stojiljkovic, I., and Berner, R. (1993).

Virulence of Yersinia enterocolitica is closely associated with siderophore production, expression of an iron-repressible outer membrane polypeptide of 65,000 Da and pesticin sensitivity. Mol. Microbiol. 8, 397–408.

2 Introduction

36

Heesemann, J., Sing, A., and Trülzsch, K. (2006). Yersinia’s stratagem: targeting innate and adaptive immune defense. Curr. Opin. Microbiol. 9, 55–61.

Heim, F., Fehlhaber, K., and Scheibner, G. (1984). [The behavior of Yersinia enterocolitica at different temperatures and at various concentrations of curing salt].Arch ExpVeterinarmed38,729–734.

Heine, W., Beckstette M., Heroven A.K., Thiemann S., Heise U., Nuss A.M., Pisano F., Strowig T., Dersch P. (2018). Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency. PloS Pathog. 14, e1006858.

Heise, T., and Dersch, P. (2006). Identification of a domain in Yersinia virulence factor YadA that is crucial for extracellular matrix-specific cell adhesion and uptake. Proc. Natl. Acad. Sci. U.S.A. 103, 3375–3380.

al-Hendy, A., Toivanen, P., and Skurnik, M. (1992). Lipopolysaccharide O side chain of Yersinia enterocolitica O:3 is an essential virulence factor in an orally infected murine model. Infect. Immun. 60, 870–875.

Herbst, K., Bujara, M., Heroven, A.K., Opitz, W., Weichert, M., Zimmermann, A., and Dersch, P.

(2009). Intrinsic thermal sensing controls proteolysis of Yersinia virulence regulator RovA. PLoS Pathog. 5, e1000435.

Heroven, A.K., Nagel, G., Tran, H.J., Parr, S., and Dersch, P. (2004). RovA is autoregulated and antagonizes H-NS-mediated silencing of invasin and rovA expression in Yersinia pseudotuberculosis.

Mol. Microbiol. 53, 871–888.

Hoiczyk, E., Roggenkamp, A., Reichenbecher, M., Lupas, A., and Heesemann, J. (2000).

Structure and sequence analysis of Yersinia YadA and Moraxella UspAs reveal a novel class of adhesins. EMBO J. 19, 5989–5999.

Hu, Z., Patel, I.R., and Mukherjee, A. (2013). Genetic analysis of the roles of agaA, agaI, and agaS genes in the N-acetyl-D-galactosamine and D-galactosamine catabolic pathways in Escherichia coli strains O157:H7 and C. BMC Microbiol. 13, 94.

Hurst, M.R.H., Becher, S.A., Young, S.D., Nelson, T.L., and Glare, T.R. (2011). Yersinia entomophaga sp. nov., isolated from the New Zealand grass grub Costelytra zealandica. Int. J. Syst.

Evol. Microbiol. 61, 844–849.

Irnov, I., Sharma, C.M., Vogel, J., and Winkler, W.C. (2010). Identification of regulatory RNAs in Bacillus subtilis. Nucleic Acids Res. 38, 6637–6651.

Isberg, R.R., Voorhis, D.L., and Falkow, S. (1987). Identification of invasin: a protein that allows enteric bacteria to penetrate cultured mammalian cells. Cell 50, 769–778.

Jalava, K., Hakkinen, M., Valkonen, M., Nakari, U.-M., Palo, T., Hallanvuo, S., Ollgren, J., Siitonen, A., and Nuorti, J.P. (2006). An outbreak of gastrointestinal illness and erythema nodosum from grated carrots contaminated with Yersinia pseudotuberculosis. J. Infect. Dis. 194, 1209–1216.

Jones, K.E., Patel, N.G., Levy, M.A., Storeygard, A., Balk, D., Gittleman, J.L., and Daszak, P.

(2008). Global trends in emerging infectious diseases. Nature 451, 990–993.

2 Introduction

37

Joutsen, S., Laukkanen-Ninios, R., Henttonen, H., Niemimaa, J., Voutilainen, L., Kallio, E.R., Helle, H., Korkeala, H., and Fredriksson-Ahomaa, M. (2017). Yersinia spp. in Wild Rodents and Shrews in Finland. Vector Borne Zoonotic Dis. 17, 303–311.

Kawano, M., Aravind, L., and Storz, G. (2007). An antisense RNA controls synthesis of an SOS-induced toxin evolved from an antitoxin. Mol. Microbiol. 64, 738–754.

Kenyon, J.J., Duda, K.A., De Felice, A., Cunneen, M.M., Molinaro, A., Laitinen, J., Skurnik, M., Holst, O., Reeves, P.R., and De Castro, C. (2016). Serotype O:8 isolates in the Yersinia pseudotuberculosis complex have different O-antigen gene clusters and produce various forms of rough LPS. Innate Immun 22, 205–217.

Keto-Timonen, R., Hietala, N., Palonen, E., Hakakorpi, A., Lindström, M., and Korkeala, H.

(2016). Cold Shock Proteins: A Minireview with Special Emphasis on Csp-family of Enteropathogenic Yersinia. Front Microbiol 7, 1151.

Kim, T., Bak, G., Lee, J., and Kim, K.-S. (2015). Systematic analysis of the role of bacterial Hfq-interacting sRNAs in the response to antibiotics. J. Antimicrob. Chemother. 70, 1659–1668.

Kim, T.-J., Young, B.M., and Young, G.M. (2008). Effect of flagellar mutations on Yersinia enterocolitica biofilm formation. Appl. Environ. Microbiol. 74, 5466–5474.

Kim, T.-J., Young, B.M., and Young, G.M. (2008). Effect of flagellar mutations on Yersinia enterocolitica biofilm formation. Appl. Environ. Microbiol. 74, 5466–5474.

Kolodziejek, A.M., Schnider, D.R., Rohde, H.N., Wojtowicz, A.J., Bohach, G.A., Minnich, S.A., and Hovde, C.J. (2010). Outer membrane protein X (Ail) contributes to Yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length. Infect. Immun.

78, 5233–5243.

Koo, J.T., Alleyne, T.M., Schiano, C.A., Jafari, N., and Lathem, W.W. (2011). Global discovery of small RNAs in Yersinia pseudotuberculosis identifies Yersinia-specific small, noncoding RNAs required for virulence. Proc. Natl. Acad. Sci. U.S.A. 108, E709-717.

Koornhof, H.J., Smego, R.A., and Nicol, M. (1999). Yersiniosis. II: The pathogenesis of Yersinia infections. Eur. J. Clin. Microbiol. Infect. Dis. 18, 87–112.

Kraehenbuhl, J.P., and Neutra, M.R. (2000). Epithelial M cells: differentiation and function. Annu.

Rev. Cell Dev. Biol. 16, 301–332.

Laitenen, O., Tuuhea, J., and Ahvonen, P. (1972). Polyarthritis associated with Yersinia enterocolitica infection. Clinical features and laboratory findings in nine cases with severe joint symptoms. Ann. Rheum. Dis. 31, 34–39.

Laitinen, O., Leirisalo, M., and Skylv, G. (1977). Relation between HLA-B27 and clinical features in patients with yersinia arthritis. Arthritis Rheum. 20, 1121–1124.

Le Guern, A.-S., Martin, L., Savin, C., and Carniel, E. (2016). Yersiniosis in France: overview and potential sources of infection. Int. J. Infect. Dis. 46, 1–7.

2 Introduction

38

Leon-Velarde, C.G., Happonen, L., Pajunen, M., Leskinen, K., Kropinski, A.M., Mattinen, L., Rajtor, M., Zur, J., Smith, D., Chen, S., et al. (2016). Yersinia enterocolitica-Specific Infection by Bacteriophages TG1 and ϕR1-RT Is Dependent on Temperature-Regulated Expression of the Phage Host Receptor OmpF. Appl. Environ. Microbiol. 82, 5340–5353.

Liu, M., Alice, A.F., Naka, H., and Crosa, J.H. (2007). The HlyU protein is a positive regulator of rtxA1, a gene responsible for cytotoxicity and virulence in the human pathogen Vibrio vulnificus. Infect.

Immun. 75, 3282–3289.

Liu, M.Y., Gui, G., Wei, B., Preston, J.F., Oakford, L., Yüksel, U., Giedroc, D.P., and Romeo, T.

(1997). The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in Escherichia coli. J. Biol. Chem. 272, 17502–17510.

MacDonald, E., Einöder-Moreno, M., Borgen, K., Thorstensen Brandal, L., Diab, L., Fossli, Ø., Guzman Herrador, B., Hassan, A.A., Johannessen, G.S., Johansen, E.J., et al. (2016). National outbreak of Yersinia enterocolitica infections in military and civilian populations associated with consumption of mixed salad, Norway, 2014. Euro Surveill. 21.

Macnab, R.M. (1999). The bacterial flagellum: reversible rotary propellor and type III export apparatus. J. Bacteriol. 181, 7149–7153.

Magistrali, C.F., Cucco, L., Manuali, E., Sebastiani, C., Farneti, S., Ercoli, L., and Pezzotti, G.

(2014). Atypical Yersinia pseudotuberculosis serotype O:3 isolated from hunted wild boars in Italy.

Vet. Microbiol. 171, 227–231.

Mäki-Ikola, O., Heesemann, J., Toivanen, A., and Granfors, K. (1997). High frequency of Yersinia antibodies in healthy populations in Finland and Germany. Rheumatol. Int. 16, 227–229.

Mandlik, A., Livny, J., Robins, W.P., Ritchie, J.M., Mekalanos, J.J., and Waldor, M.K. (2011).

RNA-Seq-based monitoring of infection-linked changes in Vibrio cholerae gene expression. Cell Host Microbe 10, 165–174.

Marcus, S.L., Brumell, J.H., Pfeifer, C.G., and Finlay, B.B. (2000). Salmonella pathogenicity islands: big virulence in small packages. Microbes Infect. 2, 145–156.

Massé, E., Escorcia, F.E., and Gottesman, S. (2003). Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev. 17, 2374–2383.

Matsumoto, H., and Young, G.M. (2006). Proteomic and functional analysis of the suite of Ysp proteins exported by the Ysa type III secretion system of Yersinia enterocolitica Biovar 1B. Mol.

Microbiol. 59, 689–706.

Matsumoto, H., and Young, G.M. (2009). Translocated effectors of Yersinia. Curr. Opin. Microbiol.

12, 94–100.

Matsuura, M., Takahashi, H., Watanabe, H., Saito, S., and Kawahara, K. (2010).

Immunomodulatory effects of Yersinia pestis lipopolysaccharides on human macrophages. Clin.

Vaccine Immunol. 17, 49–55.

2 Introduction

39

McNally, A., Thomson, N.R., Reuter, S., and Wren, B.W. (2016). “Add, stir and reduce”: Yersinia spp. as model bacteria for pathogen evolution. Nat. Rev. Microbiol. 14, 177–190.

Mikula, K.M., Kolodziejczyk, R., and Goldman, A. (2012). Yersinia infection tools-characterization of structure and function of adhesins. Front Cell Infect Microbiol 2, 169.

Miller, E.F., and Maier, R.J. (2014). Ammonium metabolism enzymes aid Helicobacter pylori acid resistance. J. Bacteriol. 196, 3074–3081.

Miller, V.L., and Falkow, S. (1988). Evidence for two genetic loci in Yersinia enterocolitica that can promote invasion of epithelial cells. Infect. Immun. 56, 1242–1248.

Miller, V.L., Beer, K.B., Heusipp, G., Young, B.M., and Wachtel, M.R. (2001). Identification of regions of Ail required for the invasion and serum resistance phenotypes.Mol.Microbiol.41,1053–1062.

Moreau, K., Lacas-Gervais, S., Fujita, N., Sebbane, F., Yoshimori, T., Simonet, M., and Lafont, F.

(2010). Autophagosomes can support Yersinia pseudotuberculosis replication in macrophages. Cell.

Microbiol. 12, 1108–1123.

Mueller, C.A., Broz, P., Müller, S.A., Ringler, P., Erne-Brand, F., Sorg, I., Kuhn, M., Engel, A., and Cornelis, G.R. (2005). The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles. Science 310, 674–676.

Murros-Kontiainen, A., Fredriksson-Ahomaa, M., Korkeala, H., Johansson, P., Rahkila, R., and Björkroth, J. (2011a). Yersinia nurmii sp. nov. Int. J. Syst. Evol. Microbiol. 61, 2368–2372.

Murros-Kontiainen, A., Johansson, P., Niskanen, T., Fredriksson-Ahomaa, M., Korkeala, H., and Björkroth, J. (2011b). Yersinia pekkanenii sp. nov. Int. J. Syst. Evol. Microbiol. 61, 2363–2367.

Muszyński, A., Rabsztyn, K., Knapska, K., Duda, K.A., Duda-Grychtoł, K., Kasperkiewicz, K., Radziejewska-Lebrecht, J., Holst, O., and Skurnik, M. (2013). Enterobacterial common antigen and O-specific polysaccharide coexist in the lipopolysaccharide of Yersinia enterocolitica serotype O:3.

Microbiology (Reading, Engl.) 159, 1782–1793.

Nagel, G., Lahrz, A., and Dersch, P. (2001). Environmental control of invasin expression in Yersinia pseudotuberculosis is mediated by regulation of RovA, a transcriptional activator of the SlyA/Hor family. Mol. Microbiol. 41, 1249–1269.

Nagel, G., Lahrz, A., and Dersch, P. (2001). Environmental control of invasin expression in Yersinia pseudotuberculosis is mediated by regulation of RovA, a transcriptional activator of the SlyA/Hor family. Mol. Microbiol. 41, 1249–1269.