Horizontally Transferred Genetic Elements and Their Role in Pathogenesis of Bacterial Disease

This article reviews the roles that laterally transferred genes (LTG) play in the virulence of bacterial pathogens. The features of LTG that allow them to be recognized in bacterial genomes are described, and the mechanisms by which LTG are transferred between and within bacteria are reviewed. Genes on plasmids, integrative and conjugative elements, prophages, and pathogenicity islands are highlighted. Virulence genes that are frequently laterally transferred include genes for bacterial adherence to host cells, type 3 secretion systems, toxins, iron acquisition, and antimicrobial resistance. The specific roles of LTG in pathogenesis are illustrated by specific reference to Escherichia coli, Salmonella, pyogenic streptococci, and Clostridium perfringens.

[1]  Tetsuya Hayashi,et al.  Escherichia coli , 1983, CABI Compendium.

[2]  Andreas Tauch,et al.  The Pan-Genome of the Animal Pathogen Corynebacterium pseudotuberculosis Reveals Differences in Genome Plasticity between the Biovar ovis and equi Strains , 2013, PloS one.

[3]  Andreas Tauch,et al.  Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains , 2011, PloS one.

[4]  C. Médigue,et al.  A Genomic Island of the Pathogen Leptospira interrogans Serovar Lai Can Excise from Its Chromosome , 2006, Infection and Immunity.

[5]  J. Timoney The pathogenic equine streptococci. , 2004, Veterinary research.

[6]  D. Bolton Verocytotoxigenic (Shiga toxin-producing) Escherichia coli: virulence factors and pathogenicity in the farm to fork paradigm. , 2011, Foodborne pathogens and disease.

[7]  L. Beutin,et al.  Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift with regard to human pathogenicity of STEC strains. , 2012, Journal of food protection.

[8]  H. Brüggemann Genomics of clostridial pathogens: implication of extrachromosomal elements in pathogenicity. , 2005, Current opinion in microbiology.

[9]  W. Maas,et al.  Naturally occurring plasmid carrying genes for enterotoxin production and drug resistance. , 1977, Science.

[10]  A. M. Pappenheimer,et al.  PHAGE-HOST RELATIONSHIPS IN NONTOXIGENIC AND TOXIGENIC DIPHTHERIA BACILLI , 1954, Journal of bacteriology.

[11]  M. Wierup The Swedish experience of the 1986 year ban of antimicrobial growth promoters, with special reference to animal health, disease prevention, productivity, and usage of antimicrobials. , 2001, Microbial drug resistance.

[12]  M. Hattori,et al.  Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. , 2001, DNA research : an international journal for rapid publication of reports on genes and genomes.

[13]  M. Stanhope,et al.  Gene Repertoire Evolution of Streptococcus pyogenes Inferred from Phylogenomic Analysis with Streptococcus canis and Streptococcus dysgalactiae , 2012, PloS one.

[14]  J. Sweasy,et al.  The cell pole: the site of cross talk between the DNA uptake and genetic recombination machinery , 2012, Critical reviews in biochemistry and molecular biology.

[15]  A. Pantosti,et al.  Identification and molecular discrimination of toxigenic and nontoxigenic diphtheria Corynebacterium strains by combined real-time polymerase chain reaction assays. , 2012, Diagnostic microbiology and infectious disease.

[16]  M. Schmidt,et al.  LEEways: tales of EPEC, ATEC and EHEC , 2010, Cellular microbiology.

[17]  D. Holden,et al.  Functions of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system effectors. , 2012, Microbiology.

[18]  J. Volf,et al.  Virulence potential of five major pathogenicity islands (SPI-1 to SPI-5) of Salmonella enterica serovar Enteritidis for chickens , 2009, BMC Microbiology.

[19]  M. Prevost,et al.  A Natural System of Chromosome Transfer in Yersinia pseudotuberculosis , 2012, PLoS genetics.

[20]  H. Seth-Smith SPI-7: Salmonella's Vi-encoding Pathogenicity Island. , 2008, Journal of infection in developing countries.

[21]  Mark P Stevens,et al.  Identification of host‐specific colonization factors of Salmonella enterica serovar Typhimurium , 2004, Molecular microbiology.

[22]  W. F. Fricke,et al.  Horizontal Gene Transfer of a ColV Plasmid Has Resulted in a Dominant Avian Clonal Type of Salmonella enterica Serovar Kentucky , 2010, PloS one.

[23]  T. van der Poll,et al.  Host–Pathogen Interaction in Invasive Salmonellosis , 2012, PLoS pathogens.

[24]  Keith A. Jolley,et al.  Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens , 2009, PLoS pathogens.

[25]  R. Friendship,et al.  Effect of plasmid pTENT2 on severity of porcine post-weaning diarrhoea induced by an O149 enterotoxigenic Escherichia coli. , 2008, Veterinary microbiology.

[26]  D. Brisson,et al.  Genetics of Borrelia burgdorferi. , 2012, Annual review of genetics.

[27]  R. Curtiss,et al.  Hybridization studies with a DNA probe derived from the virulence region of the 60 Mdal plasmid of Salmonella typhimurium. , 1989, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[28]  Hinnebusch Bj The evolution of flea-borne transmission in Yersinia pestis. , 2005 .

[29]  L. Teel,et al.  Pathogenesis of Shiga-toxin producing escherichia coli. , 2012, Current topics in microbiology and immunology.

[30]  T. Cebula,et al.  Antimicrobial Resistance-Conferring Plasmids with Similarity to Virulence Plasmids from Avian Pathogenic Escherichia coli Strains in Salmonella enterica Serovar Kentucky Isolates from Poultry , 2009, Applied and Environmental Microbiology.

[31]  Sarah Chuzeville,et al.  Characterization of a New CAMP Factor Carried by an Integrative and Conjugative Element in Streptococcus agalactiae and Spreading in Streptococci , 2012, PloS one.

[32]  S. Ochi,et al.  Nucleotide sequence analysis of the enterotoxigenic Escherichia coli Ent plasmid , 2009, DNA research : an international journal for rapid publication of reports on genes and genomes.

[33]  J. Pearson,et al.  Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements , 2011, Molecular microbiology.

[34]  F. M. Yusoff,et al.  Properties of Enterococcus faecalis, a new probiotic bacterium isolated from the intestine of snakehead fish (Channa striatus Bloch) , 2014 .

[35]  A. Weiss,et al.  Different Classes of Antibiotics Differentially Influence Shiga Toxin Production , 2010, Antimicrobial Agents and Chemotherapy.

[36]  J. Frey,et al.  Bacillus anthracis: molecular taxonomy, population genetics, phylogeny and patho-evolution. , 2011, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[37]  Ram Samudrala,et al.  Accurate Prediction of Secreted Substrates and Identification of a Conserved Putative Secretion Signal for Type III Secretion Systems , 2009, PLoS pathogens.

[38]  Mobile Genetic Elements , 1983 .

[39]  B. J. Hinnebusch,et al.  The evolution of flea-borne transmission in Yersinia pestis. , 2005, Current issues in molecular biology.

[40]  A. Maurelli,et al.  Antivirulence Genes: Insights into Pathogen Evolution through Gene Loss , 2012, Infection and Immunity.

[41]  F. Ramos-Morales,et al.  Analysis of the Expression, Secretion and Translocation of the Salmonella enterica Type III Secretion System Effector SteA , 2011, PloS one.

[42]  T. Besser,et al.  Zoonotic enterohemorrhagic Escherichia coli: A One Health perspective. , 2010, ILAR journal.

[43]  M. Lindström,et al.  Novel insights into the epidemiology of Clostridium perfringens type A food poisoning. , 2011, Food microbiology.

[44]  Guy Plunkett,et al.  The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7. , 1998, Nucleic acids research.

[45]  D. Döpfer,et al.  Evolution of the Stx2-Encoding Prophage in Persistent Bovine Escherichia coli O157:H7 Strains , 2012, Applied and Environmental Microbiology.

[46]  J. E. Peters,et al.  Identification and Characterization of Novel Salmonella Mobile Elements Involved in the Dissemination of Genes Linked to Virulence and Transmission , 2012, PloS one.

[47]  T. Johnson,et al.  Occurrence of Pathogenicity Island IAPEC-O1 Genes Among Escherichia coli Implicated in Avian Colibacillosis , 2006, Avian diseases.

[48]  G. Zon,et al.  The structural gene for tetanus neurotoxin is on a plasmid. , 1984, Science.

[49]  B. McCormick,et al.  Salmonella effector proteins and host-cell responses , 2011, Cellular and Molecular Life Sciences.

[50]  H. Christensen,et al.  Comparative genomics of multiple plasmids from APEC associated with clonal outbreaks demonstrates major similarities and identifies several potential vaccine-targets. , 2012, Veterinary microbiology.

[51]  D. Clewell Properties of Enterococcus faecalis plasmid pAD1, a member of a widely disseminated family of pheromone-responding, conjugative, virulence elements encoding cytolysin. , 2007, Plasmid.

[52]  P. Glaser,et al.  Integrative Conjugative Elements and Related Elements Are Major Contributors to the Genome Diversity of Streptococcus agalactiae , 2008, Journal of bacteriology.

[53]  Carsten Friis,et al.  Estimating variation within the genes and inferring the phylogeny of 186 sequenced diverse Escherichia coli genomes , 2012, BMC Genomics.

[54]  Fiona S. L. Brinkman,et al.  The Association of Virulence Factors with Genomic Islands , 2009, PloS one.

[55]  S. Charette,et al.  IS-mediated loss of virulence by Aeromonas salmonicida , 2013, Mobile genetic elements.

[56]  G. Węgrzyn,et al.  Altruism of Shiga toxin-producing Escherichia coli: recent hypothesis versus experimental results , 2013, Front. Cell. Inf. Microbio..

[57]  Wolf-Dietrich Hardt,et al.  Phages and the Evolution of Bacterial Pathogens: from Genomic Rearrangements to Lysogenic Conversion , 2004, Microbiology and Molecular Biology Reviews.

[58]  T. Johnson,et al.  Pyrosequencing of the Vir plasmid of necrotoxigenic Escherichia coli. , 2010, Veterinary microbiology.

[59]  F. Koch-Nolte,et al.  Actin is ADP‐ribosylated by the Salmonella enterica virulence‐associated protein SpvB , 2001, Molecular microbiology.

[60]  G. Challis,et al.  A novel streptococcal integrative conjugative element involved in iron acquisition , 2008, Molecular microbiology.

[61]  M. J. Smith,et al.  Shiga toxin of enterohemorrhagic Escherichia coli type O157:H7 promotes intestinal colonization. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[62]  X. Shi,et al.  Genetic Variations in Shiga Toxin‐Producing Abilities of Bovine and Human Escherichia coli O157:H7 , 2011, Zoonoses and public health.

[63]  P. Sansonetti,et al.  SpvC is a Salmonella effector with phosphothreonine lyase activity on host mitogen-activated protein kinases , 2008, Molecular microbiology.

[64]  Rotem Sorek,et al.  CRISPR-mediated adaptive immune systems in bacteria and archaea. , 2013, Annual review of biochemistry.

[65]  B. Segerman,et al.  Clostridium botulinum group III: a group with dual identity shaped by plasmids, phages and mobile elements , 2011, BMC Genomics.

[66]  H. Ochman,et al.  Lateral gene transfer and the nature of bacterial innovation , 2000, Nature.

[67]  Andrew C. Stewart,et al.  Genomic characterization of the Bacillus cereus sensu lato species: Backdrop to the evolution of Bacillus anthracis , 2012, Genome research.

[68]  L. Andresen Production of exfoliative toxin by isolates of Staphylococcus hyicus from different countries , 2005, Veterinary Record.

[69]  J. Fierer,et al.  The Role of the spv Genes in Salmonella Pathogenesis , 2011, Front. Microbio..

[70]  Ynte H Schukken,et al.  Comparative genomics and the role of lateral gene transfer in the evolution of bovine adapted Streptococcus agalactiae. , 2011, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[71]  J. Vila,et al.  Salmonella enterica Serovar Typhimurium Skills To Succeed in the Host: Virulence and Regulation , 2013, Clinical Microbiology Reviews.

[72]  G. Nagy,et al.  Contribution of SPI-4 genes to the virulence of Salmonella enterica. , 2007, FEMS microbiology letters.

[73]  A. Torres,et al.  Altruism of Shiga toxin-producing Escherichia coli: recent hypothesis versus experimental results , 2013 .

[74]  Robert J. Moore,et al.  NetB, a Pore-Forming Toxin from Necrotic Enteritis Strains of Clostridium perfringens , 2010, Toxins.

[75]  P. Leblond,et al.  Diversity and Mobility of Integrative and Conjugative Elements in Bovine Isolates of Streptococcusagalactiae, S. dysgalactiae subsp. dysgalactiae, and S. uberis , 2010, Applied and Environmental Microbiology.

[76]  L. Bossi,et al.  Variable assortment of prophages provides a transferable repertoire of pathogenic determinants in Salmonella , 2001, Molecular microbiology.

[77]  Tal Dagan,et al.  Trends and barriers to lateral gene transfer in prokaryotes. , 2011, Current opinion in microbiology.

[78]  P. Valentin-Weigand,et al.  Epidemiology and pathogenicity of zoonotic streptococci. , 2013, Current topics in microbiology and immunology.

[79]  G. Keefe,et al.  Streptococcus agalactiae mastitis: a review. , 1997, The Canadian veterinary journal = La revue veterinaire canadienne.

[80]  A. Torres,et al.  Pathogenicity islands of intestinal E. coli. , 2002, Current topics in microbiology and immunology.

[81]  D. Crook,et al.  Genomic islands: tools of bacterial horizontal gene transfer and evolution , 2008, FEMS microbiology reviews.

[82]  W. Goebel,et al.  Pathogenicity islands and virulence evolution in Listeria. , 2001, Microbes and infection.

[83]  T. Ochoa,et al.  Enteropathogenic Escherichia coli infection in children , 2011, Current opinion in infectious diseases.

[84]  M. P. Jackson,et al.  Cloning and expression of the exfoliative toxin B gene from Staphylococcus aureus , 1986, Journal of bacteriology.

[85]  M. Achtman,et al.  Genome Sequences and Phylogenetic Analysis of K88- and F18-Positive Porcine Enterotoxigenic Escherichia coli , 2011, Journal of bacteriology.

[86]  K. Stingl,et al.  Two steps away from novelty – principles of bacterial DNA uptake , 2011, Molecular microbiology.

[87]  M. Ohnishi,et al.  Phage conversion of exfoliative toxin A production in Staphylococcus aureus , 2000, Molecular microbiology.

[88]  M. Quail,et al.  The Genome of a Pathogenic Rhodococcus: Cooptive Virulence Underpinned by Key Gene Acquisitions , 2010, PLoS genetics.

[89]  X. Qin,et al.  The fms21 (pilA)-fms20 locus encoding one of four distinct pili of Enterococcus faecium is harboured on a large transferable plasmid associated with gut colonization and virulence. , 2010, Journal of medical microbiology.

[90]  G. Cornelis,et al.  Molecular determinants of Yersinia pathogenesis. , 1996, Microbiologia.

[91]  A. Retamal-Díaz,et al.  Roles of genomic island 3 (GI-3) BAB1_0278 and BAB1_0263 open reading frames (ORFs) in the virulence of Brucella abortus in BALB/c mice. , 2012, Veterinary microbiology.

[92]  C. Gyles,et al.  Pathogenesis of bacterial infections in animals , 2004 .

[93]  V. Burrus,et al.  Diversity of integrating conjugative elements in actinobacteria , 2012, Mobile Genetic Elements.

[94]  E. Biberstein,et al.  Serogroups and biotypes among beta-hemolytic streptococci of canine origin , 1980, Journal of clinical microbiology.

[95]  K. Morgan,et al.  Risk factors for the use of prescription antibiotics on UK broiler farms. , 2008, The Journal of antimicrobial chemotherapy.

[96]  Janice K. Wiedenbeck,et al.  Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. , 2011, FEMS microbiology reviews.

[97]  Matthew K. Waldor,et al.  Lysogenic Conversion by a Filamentous Phage Encoding Cholera Toxin , 1996, Science.

[98]  Sigal Ben-Yehuda,et al.  Intercellular Nanotubes Mediate Bacterial Communication , 2011, Cell.

[99]  B. Nagy,et al.  Enterotoxigenic Escherichia coli in veterinary medicine. , 2005, International journal of medical microbiology : IJMM.

[100]  J. Penadés,et al.  The phage-related chromosomal islands of Gram-positive bacteria , 2010, Nature Reviews Microbiology.

[101]  Arto S. Baghdayan,et al.  Horizontal transfer of virulence genes encoded on the Enterococcus faecalis pathogenicity island , 2007, Molecular microbiology.

[102]  R. Doolittle,et al.  Determining Divergence Times of the Major Kingdoms of Living Organisms with a Protein Clock , 1996, Science.

[103]  T. Johnson,et al.  Pathogenomics of the Virulence Plasmids of Escherichia coli , 2009, Microbiology and Molecular Biology Reviews.

[104]  E. Brzuszkiewicz,et al.  DNA sequence analysis of the composite plasmid pTC conferring virulence and antimicrobial resistance for porcine enterotoxigenic Escherichia coli. , 2012, International journal of medical microbiology : IJMM.

[105]  T. J. Wiles,et al.  Origins and virulence mechanisms of uropathogenic Escherichia coli. , 2008, Experimental and molecular pathology.

[106]  S. Faruque,et al.  Phage-bacterial interactions in the evolution of toxigenic Vibrio cholerae , 2012, Virulence.

[107]  J. Blom,et al.  Sequence of Two Plasmids from Clostridium perfringens Chicken Necrotic Enteritis Isolates and Comparison with C. perfringens Conjugative Plasmids , 2012, PloS one.

[108]  F. Haesebrouck,et al.  Necrotic enteritis in broilers: an updated review on the pathogenesis , 2011, Avian pathology : journal of the W.V.P.A.

[109]  B. Finlay,et al.  Molecular mechanisms of Escherichia coli pathogenicity , 2012, Nature Reviews Microbiology.

[110]  M. Stanhope,et al.  Genome characterization and population genetic structure of the zoonotic pathogen, Streptococcus canis , 2012, BMC Microbiology.

[111]  G. Węgrzyn,et al.  Hydrogen peroxide-mediated induction of the Shiga toxin-converting lambdoid prophage ST2-8624 in Escherichia coli O157:H7. , 2010, FEMS immunology and medical microbiology.

[112]  R. Redfield,et al.  Tracing the Evolution of Competence in Haemophilus influenzae , 2009, PloS one.

[113]  Matthew K. Waldor,et al.  Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow , 2010, Nature Reviews Microbiology.

[114]  B. Coombes,et al.  Type VI Secretion System-Associated Gene Clusters Contribute to Pathogenesis of Salmonella enterica Serovar Typhimurium , 2012, Infection and Immunity.

[115]  V. Eldholm,et al.  Natural genetic transformation: prevalence, mechanisms and function. , 2007, Research in microbiology.

[116]  J. Volf,et al.  SPI-1 encoded genes of Salmonella Typhimurium influence differential polarization of porcine alveolar macrophages in vitro , 2012, BMC Veterinary Research.

[117]  F. Baquero,et al.  Global Spread of the hylEfm Colonization-Virulence Gene in Megaplasmids of the Enterococcus faecium CC17 Polyclonal Subcluster , 2010, Antimicrobial Agents and Chemotherapy.

[118]  G. Splitter,et al.  Genomic Island 2 of Brucella melitensis Is a Major Virulence Determinant: Functional Analyses of Genomic Islands , 2008, Journal of bacteriology.

[119]  Robert J. Moore,et al.  Necrotic Enteritis-Derived Clostridium perfringens Strain with Three Closely Related Independently Conjugative Toxin and Antibiotic Resistance Plasmids , 2011, mBio.

[120]  A. Ralph,et al.  Group a streptococcal diseases and their global burden. , 2013, Current topics in microbiology and immunology.

[121]  J. Hacker,et al.  Genome dynamics and its impact on evolution of Escherichia coli , 2010, Medical Microbiology and Immunology.

[122]  G. Pullinger,et al.  The Pasteurella multocida toxin is encoded within a lysogenic bacteriophage , 2003, Molecular microbiology.

[123]  P. Melin Neonatal group B streptococcal disease: from pathogenesis to preventive strategies. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[124]  R. Novick,et al.  Phage-Mediated Intergeneric Transfer of Toxin Genes , 2009, Science.

[125]  J. Prescott,et al.  Identification of Accessory Genome Regions in Poultry Clostridium perfringens Isolates Carrying the netB Plasmid , 2013, Journal of bacteriology.

[126]  F. Blattner,et al.  Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[127]  J. Prescott,et al.  Identification of Novel Pathogenicity Loci in Clostridium perfringens Strains That Cause Avian Necrotic Enteritis , 2010, PloS one.

[128]  M. Chandler,et al.  Insertion Sequences , 1998, Microbiology and Molecular Biology Reviews.

[129]  A. Hendrickx,et al.  Intra- and Interspecies Genomic Transfer of the Enterococcus faecalis Pathogenicity Island , 2011, PloS one.

[130]  K. Miyamoto,et al.  Identification of Novel Clostridium perfringens Type E Strains That Carry an Iota Toxin Plasmid with a Functional Enterotoxin Gene , 2011, PloS one.

[131]  T. Johnson,et al.  Pathogenomics of the Virulence Plasmids of Escherichia coli , 2010, Microbiology and Molecular Biology Reviews.

[132]  P. Herrmann,et al.  A spontaneous genomic deletion in Listeria ivanovii identifies LIPI‐2, a species‐specific pathogenicity island encoding sphingomyelinase and numerous internalins , 2006, Molecular microbiology.

[133]  J. Parkhill,et al.  Evolution of the Rhodococcus equi vap Pathogenicity Island Seen through Comparison of Host-Associated vapA and vapB Virulence Plasmids , 2008, Journal of bacteriology.

[134]  Various pathways leading to the acquisition of antibiotic resistance by natural transformation , 2012, Mobile genetic elements.

[135]  Laura S. Frost,et al.  Mobile genetic elements: the agents of open source evolution , 2005, Nature Reviews Microbiology.

[136]  P. Christie,et al.  The expanding bacterial type IV secretion lexicon. , 2013, Research in microbiology.

[137]  Fernando de la Cruz,et al.  Mobility of Plasmids , 2010, Microbiology and Molecular Biology Reviews.

[138]  M. Kuroda,et al.  Corynebacterium ulcerans 0102 carries the gene encoding diphtheria toxin on a prophage different from the C. diphtheriae NCTC 13129 prophage , 2012, BMC Microbiology.

[139]  S. Libby,et al.  The spv genes on the Salmonella dublin virulence plasmid are required for severe enteritis and systemic infection in the natural host , 1997, Infection and immunity.

[140]  D. Radune,et al.  Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids , 2012, PloS one.

[141]  Vincent Burrus,et al.  Shaping bacterial genomes with integrative and conjugative elements. , 2004, Research in microbiology.

[142]  M. Wiedmann,et al.  FSL J1-208, a Virulent Uncommon Phylogenetic Lineage IV Listeria monocytogenes Strain with a Small Chromosome Size and a Putative Virulence Plasmid Carrying Internalin-Like Genes , 2012, Applied and Environmental Microbiology.

[143]  M. Morigi,et al.  Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction , 2010, Pediatric Nephrology.

[144]  L. Beutin,et al.  Shiga toxin-producing Escherichia coli strains from cattle as a source of the Stx2a bacteriophages present in enteroaggregative Escherichia coli O104:H4 strains. , 2013, International journal of medical microbiology : IJMM.

[145]  P. Sestili,et al.  Molecular Damage and Induction of Proinflammatory Cytokines in Human Endothelial Cells Exposed to Shiga Toxin 1, Shiga Toxin 2, and α-Sarcin , 2007, Infection and Immunity.

[146]  S. Austin,et al.  Prevalence and Significance of Plasmid Maintenance Functions in the Virulence Plasmids of Pathogenic Bacteria , 2011, Infection and Immunity.