Insights from the Whole Genome Sequence of Escherichia coli RS218 in Identifying Potential Virulence Traits Common to E. coli Causing Neonatal Meningitis and Other Extra-intestinal Diseases

Main Article Content

Subhashinie Kariyawasam Dona Saumya S. Wijetunge Robab Katani Vivek Kapur

Abstract

Escherichia coli RS218 is the prototypic strain of neonatal meningitis causing E. coli (NMEC) that has been used in many studies relevant to NMEC pathogenesis.  In the present study, the whole genome of E. coli RS218 was sequenced and compared with the genomes of eight other extraintestinal pathogenic E. coli (ExPEC) as well as with the laboratory strain of E. coli K-12. Analysis of E. coli RS218 genome revealed that it consists of a circular chromosome of 5.087 Mb in size and a 114-Kbp plasmid with an average G+C content of 50.6%. The chromosome contains 4,658 coding sequences, 88 transfer RNAs, 22 ribosomal RNAs, one clustered regularly interspaced short palindromic repeats array, and five noncoding RNAs. Escherichia coli RS218 genome demonstrated 98% nucleotide similarity to cystitis causing E. coli strain UTI89. Comparative genomic analysis identified a total of 51 genomic islands (GIs) in E. coli RS218 which were not present in the E. coli K-12 genome. Of these GIs, 16 were common to all NMEC strains studied whereas two GIs were common to all ExPEC.  The GIs common to all NMEC encode for several sugar uptake pathways, arginine/ornithine metabolism, iron uptake systems, and putative adhesins and invasins, which may contribute to NMEC pathogenesis. This study also identified NMEC-specific traits that might play a role in initial colonization of mucosal epithelia and penetration of the intestinal and blood brain barriers by NMEC.  Overall, these data will facilitate a better understanding of the genetic bases of virulence and adaptation mechanisms of ExPEC.

Article Details

How to Cite
KARIYAWASAM, Subhashinie et al. Insights from the Whole Genome Sequence of Escherichia coli RS218 in Identifying Potential Virulence Traits Common to E. coli Causing Neonatal Meningitis and Other Extra-intestinal Diseases. Medical Research Archives, [S.l.], v. 4, n. 6, oct. 2016. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/655>. Date accessed: 19 apr. 2024.
Keywords
Comparative genomics, Escherichia coli, ExPEC, Neonatal meningitis, Whole genome sequencing, Virulence traits
Section
Research Articles

References

Allsopp, L. P., Beloin, C., Moriel, D. G., Totsika, M., Ghigo, J.-M., & Schembri, M. A. (2012). Functional Heterogeneity of the UpaH Autotransporter Protein from Uropathogenic Escherichia coli. J bacteriol, 194(21), 5769-5782. doi:10.1128/jb.01264-12

Amor, K. (2000). Distribution of core oligosaccharide types in lipopolysaccharides from Escherichia coli. Infect Immun, 68(3), 1116-1124.

Antao, E.-M., Wieler, L., & Ewers, C. (2009). Adhesive threads of extraintestinal pathogenic Escherichia coli. Gut Pathogens, 1(1), 22.

Aziz, R. K., Bartels, D., Best, A. A., DeJongh, M., Disz, T., Edwards, R. A., . . . Zagnitko, O. (2008). The RAST Server: Rapid Annotations using Subsystems Technology. BMC Genomics, 9(1), 1-15. doi:10.1186/1471-2164-9-75

Bach, S. (2000). The high-pathogenicity island is present in different members of the family. FEMS microbiol lett, 183(2), 289-294. doi:10.1111/j.1574-6968.2000.tb08973.x

Bachmann, B. (2006). Escherichia coli and Salmonella: Cellular and Molecular Biology: ASM Press.

Badger, J. L., Wass, C. A., & Kim, K. S. (2000). Identification of Escherichia coli K1 genes contributing to human brain microvascular endothelial cell invasion by differential fluorescence induction. Mol Microbiol, 36(1), 174-182. doi:10.1046/j.1365-2958.2000.01840.x

Badger, J. L., Wass, C. A., Weissman, S. J., & Kim, K. S. (2000). Application of Signature-Tagged Mutagenesis for Identification of Escherichia coli K1 Genes That Contribute to Invasion of Human Brain Microvascular Endothelial Cells. Infect Immun, 68(9), 5056-5061. doi:10.1128/iai.68.9.5056-5061.2000

Benz, I., & Schmidt, M. A. (1992). Isolation and serologic characterization of AIDA-I, the adhesin mediating the diffuse adherence phenotype of the diarrhea-associated Escherichia coli strain 2787 (O126:H27). Infect Immun, 60(1), 13-18.

Benz, I., & Schmidt, M. A. (2001). Glycosylation with heptose residues mediated by the aah gene product is essential for adherence of the AIDA-I adhesin. Mol Microbiol, 40(6), 1403-1413. doi:10.1046/j.1365-2958.2001.02487.x

Bloch, C. A., Huang, S.-H., Rode, C. K., & Kim, K. S. (1996). Mapping of noninvasion TnphoA mutations on the Escherichia coli O18: K1: H7 chromosome. FEMS microbiol lett, 144(2-3), 171-176.

Bodelón, G., Palomino, C., & Fernández, L. Á. (2013). Immunoglobulin domains in Escherichia coli and other enterobacteria: from pathogenesis to applications in antibody technologies. FEMS Microbiol Rev, 37(2), 204-250. doi:10.1111/j.1574-6976.2012.00347.x

Brzuszkiewicz, E., Brüggemann, H., Liesegang, H., Emmerth, M., Ölschläger, T., Nagy, G., . . . Dobrindt, U. (2006). How to become a uropathogen: Comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc Natl Acad Sci, 103(34), 12879-12884. doi:10.1073/pnas.0603038103

Carniel, E. (1996). Characterization of a large chromosomal "high-pathogenicity island" in biotype 1B Yersinia enterocolitica. J bacteriol, 178(23), 6743-6751.

Casiano-Colón, A., & Marquis, R. E. (1988). Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance. Appl Environ Microbiol, 54(6), 1318-1324.

Chen, D., Wu, R., Bryan, T. L., & Dunaway-Mariano, D. (2009). In Vitro Kinetic Analysis of Substrate Specificity in Enterobactin Biosynthetic Lower Pathway Enzymes Provides Insight into the Biochemical Function of the Hot Dog-Fold Thioesterase EntH. Biochemistry, 48(3), 511-513. doi:10.1021/bi802207t

Croxen, M. A., & Finlay, B. B. (2010). Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Micro, 8(1), 26-38. doi:http://www.nature.com/nrmicro/journal/v8/n1/suppinfo/nrmicro2265_S1.html

Datta, D. (2003). Interaction of E. coli outer-membrane protein A with sugars on the receptors of the brain microvascular endothelial cells. Proteins, 50(2), 213-221. doi:10.1002/prot.10257

Delepelaire, P. (2004). Type I secretion in gram-negative bacteria. Biochim Biophys Acta, 1694(1–3), 149-161. doi:http://dx.doi.org/10.1016/j.bbamcr.2004.05.001

Dobrindt, U., Hentschel, U., Kaper, J. B., & Hacker, J. (2002). Genome Plasticity in Pathogenic and Nonpathogenic Enterobacteria. In J. Hacker & J. Kaper (Eds.), Pathogenicity Islands and the Evolution of Pathogenic Microbes (Vol. 264/1, pp. 157-175): Springer Berlin Heidelberg.

Fabich, A. J., Jones, S. A., Chowdhury, F. Z., Cernosek, A., Anderson, A., Smalley, D., . . . Conway, T. (2008). Comparison of Carbon Nutrition for Pathogenic and Commensal Escherichia coli Strains in the Mouse Intestine. Infect Immun, 76(3), 1143-1152. doi:10.1128/iai.01386-07

Feist, A. M. (2008). The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat biotechnol, 26(6), 659-667. doi:10.1038/nbt1401

Feldmann, F., Sorsa, L. J., 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(6), 3183-3187. doi:10.1128/iai.00656-06

Fleischmann, R. D., Adams, M. D., White, O., Clayton, R. A., Kirkness, E. F., Kerlavage, A. R., . . . Venter, J. C. (1995). Whole-Genome Random Sequencing and Assembly of Haemophilus Influenzae Rd. Science, 269(5223), 496-512. doi:10.2307/2887657

Flint, H. J. (2008). Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat Rev Microbiol, 6(2), 121-131. doi:10.1038/nrmicro1817

Gao, Q., Wang, X., Xu, H., Xu, Y., Ling, J., Zhang, D., Liu, X. (2012). Roles of iron acquisition systems in virulence of extraintestinal pathogenic Escherichia coli: salmochelin and aerobactin contribute more to virulence than heme in a chicken infection model. BMC Microbiol, 12(1), 143.

Garénaux, A., Caza, M., & Dozois, C. M. (2011). The Ins and Outs of siderophore mediated iron uptake by extra-intestinal pathogenic Escherichia coli. Vet Microbiol, 153(1–2), 89-98. doi:http://dx.doi.org/10.1016/j.vetmic.2011.05.023

Gawarzewski, I., Smits, S. H., Schmitt, L., & Jose, J. (2013). Structural comparison of the transport units of type V secretion systems. Biol Chem, 394(11), 1385-1398.

Gérard, F., Pradel, N., & Wu, L.-F. (2005). Bactericidal Activity of Colicin V Is Mediated by an Inner Membrane Protein, SdaC, of Escherichia coli. J bacteriol, 187(6), 1945-1950. doi:10.1128/jb.187.6.1945-1950.2005

Große, C., Scherer, J., Koch, D., Otto, M., Taudte, N., & Grass, G. (2006). A new ferrous iron-uptake transporter, EfeU (YcdN), from Escherichia coli. Mol Microbiol, 62(1), 120-131. doi:10.1111/j.1365-2958.2006.05326.x

Hacker, J. (1992). Role of fimbrial adhesins in the pathogenesis of Escherichia coli infections. Can J Microbiol, 38(7), 720-727.

Hammer, N. D., Schmidt, J. C., & Chapman, M. R. (2007). The curli nucleator protein, CsgB, contains an amyloidogenic domain that directs CsgA polymerization. Proc Nat Acad Sci, 104(30), 12494-12499. doi:10.1073/pnas.0703310104

Handelsman, J. (2004). Metagenomics: application of genomics to uncultured microorganisms. Microbiol Mol Biol Rev, 68(4), 669-685. doi:10.1128/mmbr.68.4.669-685.2004

Hasman, H., Chakraborty, T., & Klemm, P. (1999). Antigen-43-Mediated Autoaggregation of Escherichia coli Is Blocked by Fimbriation. J Bacteriology, 181(16), 4834-4841.

Hill, V. T. (2004). TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat. Infect Immun, 72(1), 478-488.

Hoffman, J. A. (2000). Escherichia coli K1 aslA contributes to invasion of brain microvascular endothelial cells in vitro and in vivo. Infect Immun, 68(9), 5062-5067.

Honma, Y., Fernández, R. E., & Maurelli, A. T. (2004). A DNA adenine methylase mutant of Shigella flexneri shows no significant attenuation of virulence. Microbiol, 150(4), 1073-1078. doi:10.1099/mic.0.26781-0

Hunt, S., Green, J., & Artymiuk, P. (2010). Hemolysin E (HlyE, ClyA, SheA) and Related Toxins. In G. Anderluh & J. Lakey (Eds.), Proteins Membrane Binding and Pore Formation (Vol. 677, pp. 116-126): Springer New York.

Jakes, K. S., & Cramer, W. A. (2012). Border Crossings: Colicins and Transporters. Ann Rev Genet, 46(1), 209-231. doi:doi:10.1146/annurev-genet-110711-155427

Jarvis, K. G. (1996). Secretion of extracellular proteins by enterohemorrhagic Escherichia coli via a putative type III secretion system. Infect Immun, 64(11), 4826-4829.
J
ohnson, J. R., Kuskowski, M. A., Gajewski, A., Soto, S., Horcajada, J. P., de Anta, M. T. J., & Vila, J. (2005). Extended Virulence Genotypes and Phylogenetic Background of Escherichia coli Isolates from Patients with Cystitis, Pyelonephritis, or Prostatitis. J Infect Dis, 191(1), 46-50. doi:10.1086/426450

Johnson, T. J., Wannemuehler, Y., Kariyawasam, S., Johnson, J. R., Logue, C. M., & Nolan, L. K. (2012). Prevalence of Avian-Pathogenic Escherichia coli Strain O1 Genomic Islands among Extraintestinal and Commensal E. coli Isolates. J bacteriol, 194(11), 2846-2853. doi:10.1128/jb.06375-11

Kehres, D. G., Janakiraman, A., Slauch, J. M., & Maguire, M. E. (2002). SitABCD Is the Alkaline Mn2+ Transporter of Salmonella enterica Serovar Typhimurium. J bacteriol, 184(12), 3159-3166. doi:10.1128/jb.184.12.3159-3166.2002

Khan, N. A., Wang, Y., Kim, K. J., Chung, J. W., Wass, C. A., & Kim, K. S. (2002). Cytotoxic Necrotizing Factor-1 Contributes to Escherichia coli K1 Invasion of the Central Nervous System. J BioloChem, 277(18), 15607-15612. doi:10.1074/jbc.M112224200

Kim, K. S. (2003). Neurological diseases: Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci, 4(5), 376-385. doi:10.1038/nrn1103

King, M. R., Vimr, R. P., Steenbergen, S. M., Spanjaard, L., Plunkett, G., Blattner, F. R., & Vimr, E. R. (2007). Escherichia coli K1-Specific Bacteriophage CUS-3 Distribution and Function in Phase-Variable Capsular Polysialic Acid O Acetylation. J bacteriol, 189(17), 6447-6456. doi:10.1128/jb.00657-07

Kirjavainen, V., Jarva, H., Biedzka-Sarek, M., Blom, A. M., Skurnik, M., & Meri, S. (2008). Yersinia enterocolitica Serum Resistance Proteins YadA and Ail Bind the Complement Regulator C4b-Binding Protein. PLoS Pathog, 4(8), e1000140. doi:10.1371/journal.ppat.1000140

Klemm, P., Hjerrild, L., Gjermansen, M., & Schembri, M. A. (2004). Structure-function analysis of the self-recognizing Antigen 43 autotransporter protein from Escherichia coli. Mol Microbiol, 51(1), 283-296. doi:10.1046/j.1365-2958.2003.03833.x

Klemm, P., & Schembri, M. A. (2000). Bacterial adhesins: function and structure. Intl J Med Microbiol, 290(1), 27-35. doi:http://dx.doi.org/10.1016/S1438-4221(00)80102-2

Kostakioti, M., Newman, C. L., Thanassi, D. G., & Stathopoulos, C. (2005). Mechanisms of Protein Export across the Bacterial Outer Membrane. J bacteriol, 187(13), 4306-4314. doi:10.1128/jb.187.13.4306-4314.2005

Köster, W. (1991). Iron(III) hydroxamate transport across the cytoplasmic membrane of Escherichia coli. Biol Met, 4(1), 23-32. doi:10.1007/bf01135553

Kulkarni, R., Dhakal, B. K., Slechta, E. S., Kurtz, Z., Mulvey, M. A., & Thanassi, D. G. (2009). Roles of Putative Type II Secretion and Type IV Pilus Systems in the Virulence of Uropathogenic Escherichia coli. PLoS ONE, 4(3), e4752. doi:10.1371/journal.pone.0004752

Laarmann, S., & Schmidt, M. A. (2003). The Escherichia coli AIDA autotransporter adhesin recognizes an integral membrane glycoprotein as receptor. Microbiol, 149(7), 1871-1882. doi:10.1099/mic.0.26264-0

Lehti, T. A., Bauchart, P., Heikkinen, J., Hacker, J., Korhonen, T. K., Dobrindt, U., & Westerlund-Wikström, B. (2010). Mat fimbriae promote biofilm formation by meningitis-associated Escherichia coli. Microbiol, 156(8), 2408-2417. doi:10.1099/mic.0.039610-0

Leo, J. C., & Goldman, A. (2009). The immunoglobulin-binding Eib proteins from Escherichia coli are receptors for IgG Fc. Mol Immunol, 46(8–9), 1860-1866. doi:http://dx.doi.org/10.1016/j.molimm.2009.02.024

Logue, C. M., Doetkott, C., Mangiamele, P., Wannemuehler, Y. M., Johnson, T. J., Tivendale, K. A., . . . Nolan, L. K. (2012). Genotypic and Phenotypic Traits That Distinguish Neonatal Meningitis-Associated Escherichia coli from Fecal E. coli Isolates of Healthy Human Hosts. Appl Environ Microbiol, 78(16), 5824-5830. doi:10.1128/aem.07869-11

Low, D. A. (2001). Roles of DNA adenine methylation in regulating bacterial gene expression and virulence. Infect Immun, 69(12), 7197-7204. doi:10.1128/iai.69.12.7197-7204.2001

Lu, S., Zhang, X., Zhu, Y., Kim, K. S., Yang, J., & Jin, Q. (2011). Complete Genome Sequence of the Neonatal-Meningitis-Associated Escherichia coli Strain CE10. J bacteriol, 193(24), 7005. doi:10.1128/jb.06284-11

Mangiamele, P., Nicholson, B., Wannemuehler, Y., Seemann, T., Logue, C. M., Li, G., . . . Nolan, L. K. (2013). Complete Genome Sequence of the Avian Pathogenic Escherichia coli Strain APEC O78. Genome Announc, 1(2). doi:10.1128/genomeA.00026-13

Maruvada, R., & Kim, K. S. (2012). IbeA and OmpA of Escherichia coli K1 Exploit Rac1 Activation for Invasion of Human Brain Microvascular Endothelial Cells. Infect Immun, 80(6), 2035-2041. doi:10.1128/iai.06320-11

Miethke, M. (2007). Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev, 71(3), 413-451. doi:10.1128/mmbr.00012-07

Moriel, D. G., Bertoldi, I., Spagnuolo, A., Marchi, S., Rosini, R., Nesta, B., . . . Serino, L. (2010). Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proc Nat Acad Sci, 107(20), 9072-9077. doi:10.1073/pnas.0915077107

Morozova, O., & Marra, M. A. (2008). Applications of next-generation sequencing technologies in functional genomics. Genomics, 92(5), 255-264. doi:10.1016/j.ygeno.2008.07.001

Müller, S. I. (2009). Salmochelin, the long-overlooked catecholate siderophore of Salmonella. Biometals, 22(4), 691-695. doi:10.1007/s10534-009-9217-4

Nègre, V. L., Bonacorsi, S., Schubert, S., Bidet, P., Nassif, X., & Bingen, E. (2004). The Siderophore Receptor IroN, but Not the High-Pathogenicity Island or the Hemin Receptor ChuA, Contributes to the Bacteremic Step of Escherichia coli Neonatal Meningitis. Infect Immun, 72(2), 1216-1220. doi:10.1128/iai.72.2.1216-1220.2004

Nivaskumar, M., & Francetic, O. Type II secretion system: A magic beanstalk or a protein escalator. Biochim Biophys Acta.(0). doi:http://dx.doi.org/10.1016/j.bbamcr.2013.12.020

Njoroge, J. W., Nguyen, Y., Curtis, M. M., Moreira, C. G., & Sperandio, V. (2012). Virulence Meets Metabolism: Cra and KdpE Gene Regulation in Enterohemorrhagic Escherichia coli. mBio, 3(5). doi:10.1128/mBio.00280-12

Norton, J. P., & Mulvey, M. A. (2012). Toxin-Antitoxin Systems Are Important for Niche-Specific Colonization and Stress Resistance of Uropathogenic Escherichia coli. PLoS Pathog, 8(10), e1002954. doi:10.1371/journal.ppat.1002954

Oh, J. Y., Kang, M. S., Yoon, H., Choi, H. W., An, B. K., Shin, E. G., . . . Kwon, Y. K. (2012). The embryo lethality of Escherichia coli isolates and its relationship to the presence of virulence-associated genes. Poult Sci, 91(2), 370-375.

Parreira, V. R., & Gyles, C. L. (2003). A Novel Pathogenicity Island Integrated Adjacent to the thrW tRNA Gene of Avian Pathogenic Escherichia coli Encodes a Vacuolating Autotransporter Toxin. Infect Immun, 71(9), 5087-5096. doi:10.1128/iai.71.9.5087-5096.2003

Paton, A. W., Srimanote, P., Woodrow, M. C., & Paton, J. C. (2001). Characterization of Saa, a Novel Autoagglutinating Adhesin Produced by Locus of Enterocyte Effacement-Negative Shiga-Toxigenic Escherichia coli Strains That Are Virulent for Humans. Infect Immun, 69(11), 6999-7009. doi:10.1128/iai.69.11.6999-7009.2001

Peigne, C., Bidet, P., Mahjoub-Messai, F., Plainvert, C., Barbe, V., Médigue, C., . . . Bonacorsi, S. (2009). The Plasmid of Escherichia coli Strain S88 (O45:K1:H7) That Causes Neonatal Meningitis Is Closely Related to Avian Pathogenic E. coli Plasmids and Is Associated with High-Level Bacteremia in a Neonatal Rat Meningitis Model. Infect Immun, 77(6), 2272-2284. doi:10.1128/iai.01333-08

Poolman, B., Driessen, A. J., & Konings, W. N. (1987). Regulation of arginine-ornithine exchange and the arginine deiminase pathway in Streptococcus lactis. J bacteriol, 169(12), 5597-5604.

Rasko, D. A. (2008). The pangenome structure of Escherichia coli: comparative genomic analysis of E. coli commensal and pathogenic isolates. J bacteriol, 190(20), 6881-6893. doi:10.1128/jb.00619-08

Ravi, M. (2007). Contribution of AIDA-I to the pathogenicity of a porcine diarrheagenic Escherichia coli and to intestinal colonization through biofilm formation in pigs. Vet Microbiol, 120(3-4), 308-319. doi:10.1016/j.vetmic.2006.10.035

Raymond, K. N., Dertz, E. A., & Kim, S. S. (2003). Enterobactin: An archetype for microbial iron transport. Proc Nat Acad Sci, 100(7), 3584-3588. doi:10.1073/pnas.0630018100

Robbins, J. B., McCracken, G. H., Gotschlich, E. C., Ørskov, F., Ørskov, I., & Hanson, L. A. (1974). Escherichia coli K1 Capsular Polysaccharide Associated with Neonatal Meningitis. N Engl J Med, 290(22), 1216-1220. doi:doi:10.1056/NEJM197405302902202

Runyen-Janecky, L., Dazenski, E., Hawkins, S., & Warner, L. (2006). Role and Regulation of the Shigella flexneri Sit and MntH Systems. Infect Immun, 74(8), 4666-4672. doi:10.1128/iai.00562-06

Sabri, M., Caza, M., Proulx, J., Lymberopoulos, M. H., Brée, A., Moulin-Schouleur, M., . . . Dozois, C. M. (2008). Contribution of the SitABCD, MntH, and FeoB Metal Transporters to the Virulence of Avian Pathogenic Escherichia coli O78 Strain χ7122. Infect Immun, 76(2), 601-611. doi:10.1128/iai.00789-07

Sabri, M., Léveillé, S., & Dozois, C. M. (2006). A SitABCD homologue from an avian pathogenic Escherichia coli strain mediates transport of iron and manganese and resistance to hydrogen peroxide. Microbiol, 152(3), 745-758. doi:10.1099/mic.0.28682-0

Saraoui, T., Parayre, S., Guernec, G., Loux, V., Montfort, J., Cam, A., . . . Falentin, H. (2013). A unique in vivo experimental approach reveals metabolic adaptation of the probiotic Propionibacterium freudenreichii to the colon environment. BMC Genomics, 14(1), 911.

Saukkonen, K. M., Nowicki, B., & Leinonen, M. (1988). Role of type 1 and S fimbriae in the pathogenesis of Escherichia coli O18:K1 bacteremia and meningitis in the infant rat. Infect Immun, 56(4), 892-897.

Schaible, U. E. (2004). Iron and microbial infection. Nat Rev Microbiol, 2(12), 946-953. doi:10.1038/nrmicro1046
Schubert, S. (2002). Yersinia high-pathogenicity island contributes to virulence in Escherichia coli causing extraintestinal infections. Infect Immun, 70(9), 5335-5337.

Siguier, P., Perochon, J., Lestrade, L., Mahillon, J., & Chandler, M. (2006). ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res, 34(suppl 1), D32-D36. doi:10.1093/nar/gkj014

Silver, R. P., Aaronson, W., Sutton, A., & Schneerson, R. (1980). Comparative analysis of plasmids and some metabolic characteristics of Escherichia coli K1 from diseased and healthy individuals. Infect Immun, 29(1), 200-206.

Skaar, E. P. (2010). The Battle for Iron between Bacterial Pathogens and Their Vertebrate Hosts. PLoS pathogens, 6(8), e1000949. doi:10.1371/journal.ppat.1000949

Spurbeck, R. R., Stapleton, A. E., Johnson, J. R., Walk, S. T., Hooton, T. M., & Mobley, H. L. T. (2011). Fimbrial Profiles Predict Virulence of Uropathogenic Escherichia coli Strains: Contribution of Ygi and Yad Fimbriae. Infect Immun, 79(12), 4753-4763. doi:10.1128/iai.05621-11

Stins, M. F., Prasadarao, N. V., Ibric, L., Wass, C. A., Luckett, P., & Kim, K. S. (1994). Binding characteristics of S fimbriated Escherichia coli to isolated brain microvascular endothelial cells. Am J Pathol, 145(5), 1228-1236.

Strozen, T. G., Li, G., & Howard, S. P. (2012). YghG (GspSβ) Is a Novel Pilot Protein Required for Localization of the GspSβ Type II Secretion System Secretin of Enterotoxigenic Escherichia coli. Infect Immun, 80(8), 2608-2622. doi:10.1128/iai.06394-11

Teng, C.-H., Cai, M., Shin, S., Xie, Y., Kim, K.-J., Khan, N. A., Kim, K. S. (2005). Escherichia coli K1 RS218 Interacts with Human Brain Microvascular Endothelial Cells via Type 1 Fimbria Bacteria in the Fimbriated State. Infect Immun, 73(5), 2923-2931. doi:10.1128/iai.73.5.2923-2931.2005

Teng, C.-H., Tseng, Y.-T., Maruvada, R., Pearce, D., Xie, Y., Paul-Satyaseela, M., & Kim, K. S. (2010). NlpI Contributes to Escherichia coli K1 Strain RS218 Interaction with Human Brain Microvascular Endothelial Cells. Infect Immun, 78(7), 3090-3096. doi:10.1128/iai.00034-10

Touchon, M. (2009). Organised Genome Dynamics in the Escherichia coli Species Results in Highly Diverse Adaptive Paths. PLoS genetics, 5(1), e1000344. doi:10.1371/journal.pgen.1000344

Wang, Y., Wen, Z. G., & Kim, K. S. (2004). Role of S fimbriae in Escherichia coli K1 binding to brain microvascular endothelial cells in vitro and penetration into the central nervous system in vivo. Microb Pathog, 37(6), 287-293. doi:http://dx.doi.org/10.1016/j.micpath.2004.09.002

Watts, R. E., Totsika, M., Challinor, V. L., Mabbett, A. N., Ulett, G. C., De Voss, J. J., & Schembri, M. A. (2012). Contribution of Siderophore Systems to Growth and Urinary Tract Colonization of Asymptomatic Bacteriuria Escherichia coli. Infect Immun, 80(1), 333-344. doi:10.1128/iai.05594-11

Welch, R. A., Burland, V., Plunkett, G., 3rd, Redford, P., Roesch, P., Rasko, D., . . . Blattner, F. R. (2002). Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci, 99(26), 17020-17024.

Whitfield, C., Heinrichs, D. E., Yethon, J. A., Amor, K. L., Monteiro, M. A., & Perry, M. B. (1999). Assembly of the R1-type core oligosaccharide of Escherichia coli lipopolysaccharide. J Endotox Res, 5(3), 151-156. doi:10.1177/09680519990050030901

Widenhorn, K. A., Somers, J. M., & Kay, W. W. (1989). Genetic regulation of the tricarboxylate transport operon (tctI) of Salmonella typhimurium. J bacteriol, 171(8), 4436-4441.

Wijetunge, D. S. S. (2014). Pathogenomics of neonatal meningitis causing Escherichia coli. (PhD), Pennsylvania State University. Retrieved from https://etda.libraries.psu.edu/paper/21085/

Wijetunge, D. S. S., Karunathilake, K. H. E. M., Chaudhari, A., Katani, R., Dudley, E. G., Kapur, V., . . . Kariyawasam, S. (2014). Complete nucleotide sequence of pRS218, a large virulence plasmid, that augments pathogenic potential of meningitis-associated Escherichia coli strain RS218. BMC Microbiology, 14, 203. doi:10.1186/s12866-014-0203-9

Wilson, C. G. M., Kajander, T., & Regan, L. (2005). The crystal structure of NlpI. FEBS J, 272(1), 166-179. doi:10.1111/j.1432-1033.2004.04397.x

Wyborn, N. R., Clark, A., Roberts, R. E., Jamieson, S. J., Tzokov, S., Bullough, P. A., . . . Green, J. (2004). Properties of haemolysin E (HlyE) from a pathogenic Escherichia coli avian isolate and studies of HlyE export. Microbiol, 150(5), 1495-1505. doi:10.1099/mic.0.26877-0

Xie, Y., Kolisnychenko, V., Paul-Satyaseela, M., Elliott, S., Parthasarathy, G., Yao, Y., . . . Kim, K. S. (2006). Identification and Characterization of Escherichia coli RS218–Derived Islands in the Pathogenesis of E. coli Meningitis. J Infect Dis, 194(3), 358-364. doi:10.1086/505429

Yamaguchi, Y., Park, J.-H., & Inouye, M. (2011). Toxin-Antitoxin Systems in Bacteria and Archaea. Ann Rev Genet, 45(1), 61-79. doi:doi:10.1146/annurev-genet-110410-132412

Yoshida, Y., Murakami, A., Iwai, K., & Tanaka, K. (2007). A Neural-specific F-box Protein Fbs1 Functions as a Chaperone Suppressing Glycoprotein Aggregation. J Biol Chem, 282(10), 7137-7144. doi:10.1074/jbc.M611168200

Zhou, Y., Liang, Y., Lynch, K. H., Dennis, J. J., & Wishart, D. S. (2011). PHAST: A Fast Phage Search Tool. Nucleic Acids Res, 39, W347-W352. doi:10.1093/nar/gkr485

Zhou, Y., Tao, J., Yu, H., Ni, J., Zeng, L., Teng, Q., . . . Yao, Y. (2012). Hcp Family Proteins Secreted via the Type VI Secretion System Coordinately Regulate Escherichia coli K1 Interaction with Human Brain Microvascular Endothelial Cells. Infect Immun, 80(3), 1243-1251. doi:10.1128/iai.05994-11