Ulrich Dobrindt

Loss of Regulatory Protein RfaH Attenuates Virulence of Uropathogenic Escherichia coli

ABSTRACT RfaH is a regulatory protein in Escherichia coli and Salmonella enterica serovar Typhimurium. Although it enhances expression of different factors that are proposed to play a role in bacterial virulence, a direct effect of RfaH on virulence has not been investigated so far. We report that inactivation of rfaH dramatically decreases the virulence of uropathogenic E. coli strain 536 in an ascending mouse model of urinary tract infection. The mortality rate caused by the wild-type strain in this assay is 100%, whereas that of its isogenic rfaH mutant does not exceed 18%. In the case of coinfection, the wild-type strain 536 shows higher potential to colonize the urinary tract even when it is outnumbered 100-fold by its rfaH mutant in the inoculum. In contrast to the wild-type strain, serum resistance of strain 536rfaH::cat is fully abolished. Furthermore, we give evidence that, besides a major decrease in the amount of hemin receptor ChuA (G. Nagy, U. Dobrindt, M. Kupfer, L. Emody, H. Karch, and J. Hacker, Infect. Immun. 69:1924-1928, 2001), loss of the RfaH protein results in an altered lipopolysaccharide phenotype as well as decreased expression of K15 capsule and alpha-hemolysin, whereas levels of other pathogenicity factors such as siderophores, flagella, Prf, and S fimbriae appear to be unaltered in strain 536rfaH::cat in comparison to the wild-type strain. trans complementation of the mutant strain with the rfaH gene restores wild-type levels of the affected virulence factors and consequently restitutes virulence in the mouse model of ascending urinary tract infection.

Genome Plasticity in Pathogenic and Nonpathogenic Enterobacteria

The Enterobacteriaceae comprise a distinct phylogenetic cluster that share a common ancestor with other γ-Proteobacteria. This prokaryotic family comprises 40 genera with 200 species (Garrity 2001). Within this division many representatives live in intimate association with hosts either as pathogens, as commensals or as symbionts (Steinert et al. 2000). The best-studied examples are the entero-bacteria, which comprise the clinically relevant human and animal pathogenic species Escherichia coli, Salmonella enterica, and Shigella spp., as well as Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica. The entomopathogenic bacterium Photorhabdus luminescens also belongs to the Enterobacteriaceae. This bacterium is unusual in that it combines a symbiotic life style within the guts of nematodes with a pathogenic life style that results in the killing of insects. Among the γ-Proteobacteria there are many species establishing symbiotic interactions mostly with invertebrate hosts, for example with insects, with bioluminescent squid and other marine invertebrates, and with nematodes. The genomes of several pathogens and symbionts have been sequenced recently and work is still in progress. In spite of the diverse manifestations of bacteria-host interactions, there are similar fundamental mechanisms that mediate the interaction and communication between the bacterial and eukaryotic partners (Hentschel et al. 2000; Steinert et al. 2000).

Between Pathogenicity and Commensalism

Between Commensalism and Pathogenicity:Bacterial and Host Aspects.- E. coli as an all-rounder: The thin line between commensalism and pathogenicity.- What distinguishes non-pathogenic, from medium and highly pathogenic staphylococci?.- Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung.- Lactobacillus: Host-Microbe Relationships.- Bacterial Moonlighting Proteins and Bacterial Virulence.- Symbionts and pathogens - what is the difference?.-Host-microbe Interaction in the Intestinal Tract.- Ecology and physiology of the intestinal tract.- The gut microflora and its variety of roles in health and disease.- Mammalian intestinal host-microbe relationships.- Contribution of the intestinal microbiota to human health - from birth to 100 years of age.- Subject index.

Pathogenicity Islands of Uropathogence E. Coli and Evolution of Virulence

E. coli bacteria are able to cause a large range of infectious diseases in humans. Among these are infections of the gastrointestinal tract as well as extraintestinal infections of great importance. Intestinal E. coli can be grouped in at least six different pathotypes including enterotoxigenic (ETEC), enteropathogenic (EPEC), enterohemorrhagic (EHEC) and enteroaggregative (EaggEC) E. coli. Extraintestinal E. coli fall into three groups: meningitis (MENEC), septicemia (SEPEC) and uropathogenic (UPEC) E. coli. UPECs are by far the most common cause of uncomplicated bacterial urinary tract infections (UTIs). About 80 % of all UTIs are due to E. coli. UPECs differ from non-pathogenic E. coli variants by the presence of certain virulence factors which contribute to their ability to cause disease. These are two different types of toxins, α -hemolysin (Hly) and the cytotoxic necrotizing factor 1 (CNF1), fimbrial adhesins e. g. P-, type 1 and S-fimbriae and iron-uptake systems like aerobactin, enterobactin or yersiniabactin. Furthermore, UPECs belong to certain serotypes and have the capacity to survive in human serum. About ten years ago it was detected that UPECs contain distinct blocks of DNA carrying closely linked virulence genes. Later on these structures were

Genome plasticity and infectious diseases.

Table of Contents Part I Bacterial Infections 1 Impact of Genome Plasticity on Adaptation of Escherichia coli during Urinary Bladder Colonization Ulrich Dobrindt, Jaroslaw Zdziarski, and Jorg Hacker 2 Genotypic Changes in Enterohemorrhagic Escherichia coli during Human Infection Alexander Mellmann, Martina Bielaszewska, and Helge Karch 3 Genomic Fluidity of the Human Gastric Pathogen Helicobacter pylori Niyaz Ahmed, Singamaneni Haritha Devi, Shivendra Tenguria, Mohammed Majid, Syed Asad Rahman, and Seyed E. Hasnain 4 Genome Structure and Variability in Coagulase-Negative Staphylococci Wilma Ziebuhr 5 Genome Plasticity in Legionella pneumophila and Legionella longbeachae: Impact on Host Cell Exploitation L. Gomez Valero, C. Rusniok, and C. Buchrieser 6 Genome Plasticity in Salmonella enterica and Its Relevance to Host-Pathogen Interactions Rosana B. Ferreira, Michelle M. Buckner, and B. Brett Finlay 7 Mechanisms of Genome Plasticity in Neisseria meningitidis: Fighting Change with Change Roland Schwarz, Biju Joseph, Matthias Frosch, and Christoph Schoen 8 Selfish Elements and Self-Defense in the Enterococci Kelli L. Palmer and Michael S. Gilmore Part II Viral Infections 9 Host-Driven Plasticity of the Human Immunodeficiency Virus Genome Stephen Norley and Reinhard Kurth 10 Genome Plasticity of Influenza Viruses Silke Stertz and Peter Palese 11 Plasticity of the Hepatitis C Virus Genome Joerg Timm and Michael Roggendor 12 Genome Diversity and Host Interaction of Noroviruses Eckart Schreier 13 Genome Diversity and Evolution of Rotaviruses Jelle Matthijnssens and Ulrich Desselberger 14 Genome Plasticity of Papillomaviruses Hans-Ulrich Bernard 15 Genome Plasticity of Herpesviruses: Conservative yet Flexible Mirko Trilling, Vu Thuy Khanh Le, and Hartmut Hengel Part III Parasitic and Fungal Infections 16 Genome Diversity, Population Genetics, and Evolution of Malaria Parasites Xin-zhuan Su and Deirdre A. Joy 17 The Fundamental Contribution of Genome Hypervariability to the Success of a Eukaryotic Pathogen, Trypanosoma brucei J. David Barry 18 Genome Plasticity in Candida albicans Claude Pujol and David R. Soll 19 Genome Plasticity of Aspergillus Species Thorsten Heinekamp and Axel A. Brakhage Part IV Host Susceptibility 20 DNA Polymorphisms and Their Relevance for Infections with Human Cytomegalovirus and Aspergillus fumigatus Markus Mezger, Hermann Einsele, and Juergen Loeffler 21 Host Genetic Variation, Innate Immunity, and Susceptibility to Urinary Tract Infection Bryndis Ragnarsdottir and Catharina Svanborg

CHAPTER 3 – Mobile genetic elements and pathogenicity islands encoding bacterial toxins

Genomic islands (GEIs) represent a group of distinct genetic entities. Depending on the functions and their role for a specific lifestyle of a bacterium, GEIs may be called pathogenicity, symbiosis, fitness, metabolic, or resistance islands. Furthermore, the presence of identical genes in pathogenic and non-pathogenic variants of one species, e.g., in extraintestinal pathogenic and commensal E. coli, implies that some of these encoded factors rather contribute to general adaptability, fitness, and competitiveness than to particular virulence traits. The genetic information encoded by plasmids can contain valuable genes, which may be beneficial under certain conditions, such as toxin genes, but also resistance determinants and genes coding for specific metabolic properties. This chapter illustrates that there is a structural and functional interdependence between many bacterial protein toxin genes and mobile and accessory genetic elements that promotes adaptive evolution of pathogenic bacteria. Many bacterial pathogens harbor plasmids carrying protein toxin determinants. They frequently contribute to specific combinations of virulence factors present in these strains. Bacteriophages encode a variety of toxin genes of pathogenic bacteria. The toxin genes are frequently located next to the bacteriophage attachment site, which argues for acquisition by mechanism of transduction. Plasmids and bacteriophages are elements that increase the genetic flexibility of bacteria. They contribute to the evolution of pathogens upon horizontal gene transfer followed by integration into the chromosome. The fact that toxin genes have the capacity to spread among bacterial strains and even between species is underlined by the occurrence of identical toxin determinants or those with similar functions on different genetic elements, such as chromosomes, phages, and plasmids