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Jorg Hacker - One of the best experts on this subject based on the ideXlab platform.
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The Concept of Pathogenicity Islands
Pathogenicity Islands and Other Mobile Virulence Elements, 2014Co-Authors: Jorg Hacker, James B KaperAbstract:In the early 1980s it was discovered that chromosomal regions may carry blocks of virulence-associated genes and may differ between related members of certain species or genera. These regions were termed Pathogenicity Islands (PAIs). The basic observation leading to the concept of PAIs was the finding that particular genomic regions of pathogens carry virulence-associated genes together with loci whose presence strongly indicates horizontal gene transfer of these regions between different species or even genera. PAIs occur in the genomes of various pathogens with the capacity to cause infections not only in humans but also in animals and even in plants. The list of PAIs described up to now includes those in bacteria for which frequent gene transfer via plasmids, bacteriophages, and conjugative transposons has been described. The existence of PAIs in eukaryotic pathogens can be predicted, because gene transfer also exists in eukaryotic organisms, transposable elements frequently occur, and retroviruses have a tendency to integrate into tRNA genes. It is now accepted that the generation of PAIs often starts with the integration of plasmids, phages, conjugative transposons, or cointegrates of these into specific target genes, preferentially on the chromosomes.
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delineation of the recombination sites necessary for integration of Pathogenicity Islands ii and iii into the escherichia coli 536 chromosome
Molecular Microbiology, 2008Co-Authors: Ulrich Dobrindt, Bianca Hochhut, Barbara Middendorf, Caroline Wilde, Didier Mazel, Frederique Le Roux, Elisabeth Carniel, Jorg HackerAbstract:In uropathogenic Escherichia coil strain 536, six Pathogenicity Islands (PAls) encode key virulence factors. All PAls except PAI IV 536 are flanked by direct repeats and four of them encode integrases responsible for their chromosomal excision. To study recombination sites used for the integration by PAI II 536 and III 536 integrases, we measured site-specific recombination between the chromosomal integration site attB, and the PAI-specific attachment site attP. We show that PAI III 536 IntB, but not IntA, mediates PAI III 536 integration. Studies of integrative recombination sites of both PAls show that, when using a large cognate attP site (839 bp for PAI II 536 and 268 bp for PAI III 536 ), PAI II 536 and III 536 attB sites could be reduced to 16 bp and 20 bp, respectively, without affecting recombination. Further reduction to 14 bp for PAI II 536 and 13 bp for PAI III 536 diminished recombination efficiency. Surprisingly, attP sites could also be reduced to 14 bp (PAI II 536 ) and 20 bp (PAI III 536 ). The integration host factor (IHF) and the DNA-bending HU protein do not influence PAI II 536 recombination, but IHF enhances PAI-III 536 excision and negatively affects its integration. These data suggest that PAI intasomes differ from those of lambda and P4 integrase paradigms.
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impact of Pathogenicity Islands in bacterial diagnostics
Apmis, 2004Co-Authors: Tobias A Oelschlaeger, Jorg HackerAbstract:Pathogenicity Islands (PAIs) are a distinct class of genomic Islands (GEIs), which are acquired by horizontal gene transfer. PAIs harbour virulence genes and some, in addition, antibiotic resistance genes. More often genes conferring antibiotic resistance are encoded by GEIs not containing virulence genes. Both types of genetic elements are found in genomes of various human, animal and plant pathogens. There are PAIs and GEIs which are specific for a certain serotype(s), strain, or pathotype of a species. Furthermore, there are also PAIs which are more widespread and found in bacterial pathogens causing a certain pathogenic effect in the host. Even the lack of a certain PAI might be characteristic for a defined subspecies. Obviously, PAIs can be used as markers for diagnostic purposes to help identify a certain bacterial pathogen, subtype it, estimate the pathogenic potential, and in some cases predict its antibiotic resistance. This all might be achieved for known PAIs/GEIs without cultivating the microorganism of interest by employing PCR and/or DNA-chip technology. Even yet unknown PAIs can be identified in silico if the genome sequence of the bacterial pathogen under investigation is known. The more PAIs and antibiotic harbouring GEIs are identified and characterized the greater will be the benefits also for diagnostics.
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instability of Pathogenicity Islands in uropathogenic escherichia coli 536
Journal of Bacteriology, 2004Co-Authors: Barbara Middendorf, Ulrich Dobrindt, Bianca Hochhut, Gabriele Blumoehler, Kristina Leipold, Jorg HackerAbstract:The uropathogenic Escherichia coli strain 536 carries at least five genetic elements on its chromosome that meet all criteria characteristic of Pathogenicity Islands (PAIs). One main feature of these distinct DNA regions is their instability. We applied the so-called island-probing approach and individually labeled all five PAIs of E. coli 536 with the counterselectable marker sacB to evaluate the frequency of PAI-negative colonies under the influence of different environmental conditions. Furthermore, we investigated the boundaries of these PAIs. According to our experiments, PAI II536 and PAI III536 were the most unstable Islands followed by PAI I536 and PAI V536, whereas PAI IV536 was stable. In addition, we found that deletion of PAI II536 and PAI III536 was induced by several environmental stimuli. Whereas excision of PAI I536, PAI II536, and PAI V536 was based on site-specific recombination between short direct repeat sequences at their boundaries, PAI III536 was deleted either by site-specific recombination or by homologous recombination between two IS100-specific sequences. In all cases, deletion is thought to lead to the formation of nonreplicative circular intermediates. Such extrachromosomal derivatives of PAI II536 and PAI III536 were detected by a specific PCR assay. Our data indicate that the genome content of uropathogenic E. coli can be modulated by deletion of PAIs.
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genomic Islands in pathogenic and environmental microorganisms
Nature Reviews Microbiology, 2004Co-Authors: Ulrich Dobrindt, Ute Hentschel, Bianca Hochhut, Jorg HackerAbstract:Horizontal gene transfer is an important mechanism for the evolution of microbial genomes. Pathogenicity Islands — mobile genetic elements that contribute to rapid changes in virulence potential — are known to have contributed to genome evolution by horizontal gene transfer in many bacterial pathogens. Increasing evidence indicates that equivalent elements in non-pathogenic species — genomic Islands — are important in the evolution of these bacteria, influencing traits such as antibiotic resistance, symbiosis and fitness, and adaptation in general. This review discusses the recent lessons that have been learned from Pathogenicity Islands in pathogenic microorganisms and how they apply to the role of genomic Islands in commensal, symbiotic and environmental bacteria.
Ulrich Dobrindt - One of the best experts on this subject based on the ideXlab platform.
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sub inhibitory concentrations of sos response inducing antibiotics stimulate integrase expression and excision of Pathogenicity Islands in uropathogenic escherichia coli strain 536
International Journal of Medical Microbiology, 2020Co-Authors: Marco Chitto, Michael Berger, Luisa Klotz, Ulrich DobrindtAbstract:Abstract Urinary tract infections are one of the most common bacterial infections and a major public health problem. The predominant causative agents are uropathogenic Escherichia coli. These strains differ from commensal E. coli by the presence of additional horizontally acquired chromosomal material, so-called Pathogenicity Islands, which encode traits that promote efficient bacterial colonization of the urinary tract. Uropathogenic model strain E. coli 536 possesses six archetypal Pathogenicity Islands. Bacteriophage-like integrases encoded by each Pathogenicity island contribute to island instability. To learn more about the stability of these six Islands and factors controlling their stability we constructed two chromosomal reporter systems for the measurement of island loss, as well as for the measurement of the promoter activity of the six island-associated integrase genes at the population level. We used these reporter gene modules to analyze the role of SOS response in island instability. Tests with subinhibitory concentrations of different antibiotics, including many drugs commonly used for the treatment of urinary tract infection, indicated that only SOS response-inducing antibiotics led to an increased loss of Islands which was always associated with an increase in the bacterial subpopulations showing high integrase promoter activity. This suggests that island excision correlates with the expression of the cognate integrase. Our reporter modules are valuable tools to investigate the impact of various growth conditions on genome plasticity. Furthermore, a better understanding of the conditions, which affect bacterial integrase expression may open ways to specifically manipulate the genome content of bacterial pathogens by increasing Pathogenicity island deletion rates in infecting or colonizing bacteria, thus leading to the attenuation of bacterial pathogens.
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pathophysiology of escherichia coli pneumonia respective contribution of Pathogenicity Islands to virulence
International Journal of Medical Microbiology, 2018Co-Authors: Mathilde Phillipshoulbracq, Stephane Gaudry, Jonathan Messika, Dimitri Margetis, Jeremie Chatel, Deborah R Yoderhimes, Ulrich Dobrindt, Arnaud Foucrier, Jean Damien Ricard, Erick DenamurAbstract:Abstract Ventilator-associated pneumonia (VAP) remains the most frequent life-threatening nosocomial infection. Enterobacteriaceae including Escherichia coli are increasingly involved. If a cumulative effect of Pathogenicity Islands (PAIs) has been shown for E. coli virulence in urinary tract or systemic infections, very little is known regarding pathophysiology of E. coli pneumonia. This study aimed to determine the role of each of the 7 PAIs present in pathogenic E. coli strain 536 in pneumonia pathophysiology. We used mutant strains to screen pathophysiological role of PAI in a rat pneumonia model. We also test individual gene mutants within PAI identified to be involved in pneumonia pathogenesis. Finally, we determined the prevalence of these genes of interest in E. coli isolates from feces and airways of ventilated patients. Only PAIs I and III were significantly associated with rat pneumonia Pathogenicity. Only the antigen-43 (Ag43) gene in PAI III was significantly associated with bacterial Pathogenicity. The prevalence of tested genes in fecal and airway isolates of ventilated patients did not differ between isolates. In contrast, genes encoding Ag43, the F17-fimbriae subunits, HmuR and SepA were more prevalent in VAP isolates with statistical significance for hmuR when compared to airway colonizing isolates. The E. coli PAIs involved in lung Pathogenicity differed from those involved in urinary tract and bloodstream infections. Overall, extraintestinal E. coli virulence seems to rely on a combination of numerous virulence genes that have a cumulative effect depending on the infection site.
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delineation of the recombination sites necessary for integration of Pathogenicity Islands ii and iii into the escherichia coli 536 chromosome
Molecular Microbiology, 2008Co-Authors: Ulrich Dobrindt, Bianca Hochhut, Barbara Middendorf, Caroline Wilde, Didier Mazel, Frederique Le Roux, Elisabeth Carniel, Jorg HackerAbstract:In uropathogenic Escherichia coil strain 536, six Pathogenicity Islands (PAls) encode key virulence factors. All PAls except PAI IV 536 are flanked by direct repeats and four of them encode integrases responsible for their chromosomal excision. To study recombination sites used for the integration by PAI II 536 and III 536 integrases, we measured site-specific recombination between the chromosomal integration site attB, and the PAI-specific attachment site attP. We show that PAI III 536 IntB, but not IntA, mediates PAI III 536 integration. Studies of integrative recombination sites of both PAls show that, when using a large cognate attP site (839 bp for PAI II 536 and 268 bp for PAI III 536 ), PAI II 536 and III 536 attB sites could be reduced to 16 bp and 20 bp, respectively, without affecting recombination. Further reduction to 14 bp for PAI II 536 and 13 bp for PAI III 536 diminished recombination efficiency. Surprisingly, attP sites could also be reduced to 14 bp (PAI II 536 ) and 20 bp (PAI III 536 ). The integration host factor (IHF) and the DNA-bending HU protein do not influence PAI II 536 recombination, but IHF enhances PAI-III 536 excision and negatively affects its integration. These data suggest that PAI intasomes differ from those of lambda and P4 integrase paradigms.
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instability of Pathogenicity Islands in uropathogenic escherichia coli 536
Journal of Bacteriology, 2004Co-Authors: Barbara Middendorf, Ulrich Dobrindt, Bianca Hochhut, Gabriele Blumoehler, Kristina Leipold, Jorg HackerAbstract:The uropathogenic Escherichia coli strain 536 carries at least five genetic elements on its chromosome that meet all criteria characteristic of Pathogenicity Islands (PAIs). One main feature of these distinct DNA regions is their instability. We applied the so-called island-probing approach and individually labeled all five PAIs of E. coli 536 with the counterselectable marker sacB to evaluate the frequency of PAI-negative colonies under the influence of different environmental conditions. Furthermore, we investigated the boundaries of these PAIs. According to our experiments, PAI II536 and PAI III536 were the most unstable Islands followed by PAI I536 and PAI V536, whereas PAI IV536 was stable. In addition, we found that deletion of PAI II536 and PAI III536 was induced by several environmental stimuli. Whereas excision of PAI I536, PAI II536, and PAI V536 was based on site-specific recombination between short direct repeat sequences at their boundaries, PAI III536 was deleted either by site-specific recombination or by homologous recombination between two IS100-specific sequences. In all cases, deletion is thought to lead to the formation of nonreplicative circular intermediates. Such extrachromosomal derivatives of PAI II536 and PAI III536 were detected by a specific PCR assay. Our data indicate that the genome content of uropathogenic E. coli can be modulated by deletion of PAIs.
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genomic Islands in pathogenic and environmental microorganisms
Nature Reviews Microbiology, 2004Co-Authors: Ulrich Dobrindt, Ute Hentschel, Bianca Hochhut, Jorg HackerAbstract:Horizontal gene transfer is an important mechanism for the evolution of microbial genomes. Pathogenicity Islands — mobile genetic elements that contribute to rapid changes in virulence potential — are known to have contributed to genome evolution by horizontal gene transfer in many bacterial pathogens. Increasing evidence indicates that equivalent elements in non-pathogenic species — genomic Islands — are important in the evolution of these bacteria, influencing traits such as antibiotic resistance, symbiosis and fitness, and adaptation in general. This review discusses the recent lessons that have been learned from Pathogenicity Islands in pathogenic microorganisms and how they apply to the role of genomic Islands in commensal, symbiotic and environmental bacteria.
James B Kaper - One of the best experts on this subject based on the ideXlab platform.
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Pathogenicity Islands and Other Mobile Genetic Elements of Diarrheagenic Escherichia coli
Pathogenicity Islands and Other Mobile Virulence Elements, 2014Co-Authors: James B Kaper, Jay L. Mellies, James P. NataroAbstract:This chapter focuses on diarrheagenic Escherichia coli strains and the various Pathogenicity Islands (PAIs) and other mobile genetic elements that differentiate these pathogens from normal-flora E. coli. At least six categories of diarrheagenic E. coli strains have been defined. Five of these categories, enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), and enteroinvasive E. coli (EIEC), are reviewed in the chapter. A sixth category, diffusely adherent E. coli (DAEC), is a heterogeneous group of organisms, and epidemiological studies have given conflicting results about the true clinical significance of these strains. Mobile genetic elements encoding virulence factors in human diarrheagenic E. coli are listed in the chapter. The majority of EPEC strains associated with diarrhea possess the EPEC adherence factor (EAF) plasmid and are referred to as typical EPEC strains, while EPEC strains that do not possess EAF plasmids are referred to as atypical EPEC strains. The majority of genes within this region have homology to transposons and insertion elements (IS elements), although these elements are apparently incomplete and nonfunctional. The great variety of mobile genetic elements present in diarrheagenic E. coli , including plasmids, bacteriophages, transposons, and PAIs, on a K-12 backbone with so many horizontally transferred regions indicates an enormous genomic plasticity that complicates the efforts to categorize the existing subgroups into sharply delineated pathotypes and the attempts to predict what novel combination of virulence factors may emerge in the future.
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The Concept of Pathogenicity Islands
Pathogenicity Islands and Other Mobile Virulence Elements, 2014Co-Authors: Jorg Hacker, James B KaperAbstract:In the early 1980s it was discovered that chromosomal regions may carry blocks of virulence-associated genes and may differ between related members of certain species or genera. These regions were termed Pathogenicity Islands (PAIs). The basic observation leading to the concept of PAIs was the finding that particular genomic regions of pathogens carry virulence-associated genes together with loci whose presence strongly indicates horizontal gene transfer of these regions between different species or even genera. PAIs occur in the genomes of various pathogens with the capacity to cause infections not only in humans but also in animals and even in plants. The list of PAIs described up to now includes those in bacteria for which frequent gene transfer via plasmids, bacteriophages, and conjugative transposons has been described. The existence of PAIs in eukaryotic pathogens can be predicted, because gene transfer also exists in eukaryotic organisms, transposable elements frequently occur, and retroviruses have a tendency to integrate into tRNA genes. It is now accepted that the generation of PAIs often starts with the integration of plasmids, phages, conjugative transposons, or cointegrates of these into specific target genes, preferentially on the chromosomes.
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Pathogenicity Islands and the evolution of pathogenic microbes
2002Co-Authors: Jorg Hacker, James B KaperAbstract:Helicobacter pylori: Impact of gene transfer and the role of the cag Pathogenicity Islands for host adaptation and virulence.- The genus Neisseria: population structure, genome plasticity, and evolution of Pathogenicity.- Genomic Islands of Dichelobacter nodosus.- Phages and other mobile virulence elements in gram-positive pathogens.- Genome structure and evolution of the Bacillus cereus group.- Pathogenicity Islands and virulence plasmids of bacterial plant pathogens.- Genome structure of pathogenic fungi.- Impact of integrons and transposons on the evolution of resistance and virulence.- Subject index.
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Pathogenicity Islands of intestinal e coli
Current Topics in Microbiology and Immunology, 2002Co-Authors: Alfredo G Torres, James B KaperAbstract:Escherichia coli is a consistent inhabitant of the human colonic flora, and it is the predominant facultative organism in the human gastrointestinal tract; however, it makes up a very small proportion of the total intestinal bacterial content, which is dominated by anaerobic species. The regular presence of E. coli in the human intestine and feces has led to tracking the bacterium in nature as an indicator of fecal pollution and water contamination. This is especially important in developing countries, where E. coli infections are one of the leading causes of infant and childhood morbidity and mortality due to ingestion of contaminated food and water. As a pathogen, E. coli, is best known for its ability to cause diarrhea. Five main categories of E. coli that cause diarrheal diseases are now recognized: enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), and enteroinvasive E. coli (EIEC). The ability of each category to cause disease depends on a specific array of genes encoding virulence factors. These virulence factors are usually encoded on bacteriophages, plasmids, transposons, and Pathogenicity Islands (PAIs) (reviewed in Kaper et al. 1999). In this chapter, we will focus on describing the main categories of diarrheagenic E. coli strains and their various PAIs that differentiate these organisms from nonpathogenic E. coli strains (Table 1). A sixth category not discussed in this chapter, diffusely adherent E. coli (DAEC), is a heterogeneous group of organisms with conflicting results about their significance in pathogenesis and with no PAIs yet reported. Additional categories have been suggested, but conclusive epidemiological and clinical information is so far lacking for the consideration of these diarrheagenic E. coli strains as new major categories. A complete overview of the pathogenesis, epidemiology, clinical significance, detection, and diagnosis of these categories of diarrheagenic E. coli strains has recently been published (Nataro and Kaper 1998).
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Pathogenicity Islands and the Evolution of Microbes
Annual review of microbiology, 2000Co-Authors: Jorg Hacker, James B KaperAbstract:Virulence factors of pathogenic bacteria (adhesins, toxins, invasins, protein secretion systems, iron uptake systems, and others) may be encoded by particular regions of the prokaryotic genome termed Pathogenicity Islands. Pathogenicity Islands were first described in human pathogens of the species Escherichia coli, but have recently been found in the genomes of various pathogens of humans, animals, and plants. Pathogenicity Islands comprise large genomic regions [10-200 kilobases (kb) in size] that are present on the genomes of pathogenic strains but absent from the genomes of nonpathogenic members of the same or related species. The finding that the G+C content of Pathogenicity Islands often differs from that of the rest of the genome, the presence of direct repeats at their ends, the association of Pathogenicity Islands with transfer RNA genes, the presence of integrase determinants and other mobility loci, and their genetic instability argue for the generation of Pathogenicity Islands by horizontal gene transfer, a process that is well known to contribute to microbial evolution. In this article we review these and other aspects of Pathogenicity Islands and discuss the concept that they represent a subclass of genomic Islands. Genomic Islands are present in the majority of genomes of pathogenic as well as nonpathogenic bacteria and may encode accessory functions which have been previously spread among bacterial populations.
Richard P. Novick - One of the best experts on this subject based on the ideXlab platform.
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Pathogenicity Islands and Their Role in Staphylococcal Biology.
Microbiology spectrum, 2019Co-Authors: Richard P. NovickAbstract:Pathogenicity Islands are members of a vast collection of genomic Islands that encode important virulence, antibiotic resistance and other accessory functions and have a critical role in bacterial gene transfer. Staphylococcus aureus is host to a large family of such Islands, known as SaPIs, which encode super antigen and other virulence determinants, are mobilized by helper phages and transferred at extremely high frequencies. They benefit their host cells by interfering with phage predation and enhancing horizontal gene transfer. This chapter describes their life cycle, the bases of their phage interference mechanisms, their transfer system and their conversion to antibacterial agents for treatment ofstaphylococcal infections.
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conversion of staphylococcal Pathogenicity Islands to crispr carrying antibacterial agents that cure infections in mice
Nature Biotechnology, 2018Co-Authors: Geeta Ram, Richard P. Novick, Hope F Ross, Ivelisse Rodriguezpaga, Dunrong JiangAbstract:Staphylococcus aureus and other staphylococci continue to cause life-threatening infections in both hospital and community settings. They have become increasingly resistant to antibiotics, especially β-lactams and aminoglycosides, and their infections are now, in many cases, untreatable. Here we present a non-antibiotic, non-phage method of treating staphylococcal infections by engineering of the highly mobile staphylococcal Pathogenicity Islands (SaPIs). We replaced the SaPIs' toxin genes with antibacterial cargos to generate antibacterial drones (ABDs) that target the infecting bacteria in the animal host, express their cargo, kill or disarm the bacteria and thus abrogate the infection. Here we have constructed ABDs with either a CRISPR-Cas9 bactericidal or a CRISPR-dCas9 virulence-blocking module. We show that both ABDs block the development of a murine subcutaneous S. aureus abscess and that the bactericidal module rescues mice given a lethal dose of S. aureus intraperitoneally.
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staphylococcal Pathogenicity Islands movers and shakers in the genomic firmament
Current Opinion in Microbiology, 2017Co-Authors: Richard P. Novick, Geeta RamAbstract:The staphylococcal Pathogenicity Islands (SaPIs) are highly mobile 15kb genomic Islands that carry superantigen genes and other virulence factors and are mobilized by helper phages. Helper phages counteract the SaPI repressor to induce the SaPI replication cycle, resulting in encapsidation in phage like particles, enabling high frequency transfer. The SaPIs split from a protophage lineage in the distant past, have evolved a variety of novel and salient features, and have become an invaluable component of the staphylococcal genome. This review focuses on recent studies describing three different mechanisms of SaPI interference with helper phage reproduction and other studies demonstrating that helper phage mutations to resistance against this interference impact phage evolution. Also described are recent results showing that SaPIs contribute in a major way to lateral transfer of host genes as well as enabling their own transfer. SaPI-like elements, readily identifiable in the bacterial genome, are widespread throughout the Gram-positive cocci, though functionality has thus far been demonstrated for only a single one of these.
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The Floating (Pathogenicity) Island: A Genomic Dessert.
Trends in genetics : TIG, 2015Co-Authors: Richard P. Novick, Geeta RamAbstract:Among the prokaryotic genomic Islands (GIs) involved in horizontal gene transfer (HGT) are the classical Pathogenicity Islands, including the integrative and conjugative elements (ICEs), the gene-transfer agents (GTAs), and the staphylococcal Pathogenicity Islands (SaPIs), the primary focus of this review. While the ICEs and GTAs mediate HGT autonomously, the SaPIs are dependent on specific phages. The ICEs transfer primarily their own DNA, the GTAs exclusively transfer unlinked host DNA, and the SaPIs combine the capabilities of both. Thus the SaPIs derive their importance from the genes they carry (their genetic cargo) and the genes they move. They act not only as versatile high-frequency mobilizers but also as mediators of phage interference and consequently are major benefactors of their host bacteria.
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moonlighting bacteriophage proteins derepress staphylococcal Pathogenicity Islands
Nature, 2010Co-Authors: Maria Angeles Tormomas, Richard P. Novick, Ignacio Mir, Archana Shrestha, Sandra M Tallent, Susana Campoy, Inigo Lasa, Jordi Barbe, Gail E Christie, Jose R PenadesAbstract:Toxic shock syndrome is a rare, potentially fatal illness that can be caused by the release of toxins from Staphylococcus bacteria. The toxic particles are encoded by discrete genetic units called Pathogenicity Islands, which reside passively in the host chromosome, under the control of the global repressor Stl, unless activated by a helper phage. It is now shown that a non-essential and specific protein from the helper phage 80α is responsible for de-repression of the Pathogenicity island, thereby providing the mechanism for the first step of its mobilization. The proteins involved are 'moonlighters', because they have two different and genetically distinct activities. Through a remarkable evolutionary adaptation, various related Pathogenicity Islands co-opt entirely unrelated phage proteins to aid in their mobilization. Staphylococcal superantigens can lead to toxic shock syndrome. They are encoded on Pathogenicity Islands and with the aid of helper phages can be excised and packaged into highly transmissable phage particles. Here it is shown that a specific, non-essential helper phage protein is responsible for derepression of the Pathogenicity island, thereby providing the mechanism for the first step of its mobilization. Staphylococcal superantigen-carrying Pathogenicity Islands (SaPIs) are discrete, chromosomally integrated units of ∼15 kilobases that are induced by helper phages to excise and replicate. SaPI DNA is then efficiently encapsidated in phage-like infectious particles, leading to extremely high frequencies of intra- as well as intergeneric transfer1,2,3. In the absence of helper phage lytic growth, the island is maintained in a quiescent prophage-like state by a global repressor, Stl, which controls expression of most of the SaPI genes4. Here we show that SaPI derepression is effected by a specific, non-essential phage protein that binds to Stl, disrupting the Stl–DNA complex and thereby initiating the excision-replication-packaging cycle of the island. Because SaPIs require phage proteins to be packaged5,6, this strategy assures that SaPIs will be transferred once induced. Several different SaPIs are induced by helper phage 80α and, in each case, the SaPI commandeers a different non-essential phage protein for its derepression. The highly specific interactions between different SaPI repressors and helper-phage-encoded antirepressors represent a remarkable evolutionary adaptation involved in Pathogenicity island mobilization.
Michael Hensel - One of the best experts on this subject based on the ideXlab platform.
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Cooperation of Salmonella Pathogenicity Islands 1 and 4 is required to breach epithelial barriers.
Cellular microbiology, 2008Co-Authors: Roman G Gerlach, Nuno Cláudio, Manfred Rohde, Daniela Jäckel, Carolin Wagner, Michael HenselAbstract:Summary Invasion is an important microbial virulence strategy to overcome the barrier formed by polarized epithe- lial cells. Salmonella enterica is a food-borne patho- gen that deploys a type III secretion system for the manipulation of the actin cytoskeleton and to trigger internalization into epithelial cells. Here we show that this function is not sufficient to enter polarized cells and report that penetration of epithelia from the luminal side requires both the type III secretion system and novel virulence functions conferred by Salmonella Pathogenicity island 4. Salmonella Pathogenicity island 4 encodes a type I secretion system for the giant non-fimbrial adhesin SiiE that mediates intimate contact of Salmonella to microvilli on the apical membrane. Mutant strains lacking SiiE fail to invade polarized cells, to destroy epithelial barrier functions and to efface the apical brush border. Deletion analyses of repetitive domains in SiiE indicate that the large size of the adhesin is of functional importance. Our observations demon- strate that efficient penetration of epithelial barriers requires the cooperative activity of two Salmonella Pathogenicity Islands encoding different secretion systems. These findings underline the role of the epithelial brush border and reveal a new mechanism used by bacterial pathogens to overcome this barrier.
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salmonella Pathogenicity Islands in host specificity host pathogen interactions and antibiotics resistance of salmonella enterica
Berliner Und Munchener Tierarztliche Wochenschrift, 2007Co-Authors: Roman G Gerlach, Michael HenselAbstract:Salmonella enterica is a pathogen highly successful in causing a variety of gastrointestinal and systemic diseases in animals and humans. While some serovars of S. enterica are able to infect a broad range of host organisms, other serovars are highly restricted to specific host species. The colonization of hosts by S. enterica depends on the function of a large number of virulence determinants. The molecular analyses of virulence genes demonstrated that most of these loci are clustered within Salmonella Pathogenicity Islands (SPI). SPI1 and SPI2 each encode type III secretion systems (T355) that confer main virulence traits of S. enterica, i.e. invasion, enteropathogenesis and intracellular survival and proliferation. Further SPI encode factors that contribute to intracellular survival, different types of adhesins, or effector proteins of the SPI1-T3SS or SPI2-T3SS. The availability of genome sequences of several serovars of S. enterica also revealed serovar-specific SPI. In this review, the main characteristics of the currently known SPI are summarized with focus on their roles in various animal hosts and putative functions in human infections.
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Evolution of Pathogenicity Islands of Salmonella enterica.
International journal of medical microbiology : IJMM, 2004Co-Authors: Michael HenselAbstract:Virulence genes located on Pathogenicity Islands play a crucial role in the pathogenesis of Salmonella enterica infections. Salmonella Pathogenicity Islands (SPI) contribute to host cell invasion and intracellular pathogenesis. At present, 12 SPI have been described. Although size, structure and function of these SPI, as well as the distribution in Salmonella subspecies and serovars can be markedly different, several common motifs are present among SPI. In this review, the characteristics of SPI are described with focus on the evolution of these genetic elements.
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Pathogenicity Islands in bacterial pathogenesis
Clinical Microbiology Reviews, 2004Co-Authors: Herbert Schmidt, Michael HenselAbstract:In this review, we focus on a group of mobile genetic elements designated Pathogenicity Islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic Islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the Pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections.
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Salmonella Pathogenicity Islands encoding type III secretion systems.
Microbes and infection, 2001Co-Authors: Imke Hansen-wester, Michael HenselAbstract:Salmonella enterica harbours two Salmonella Pathogenicity Islands (SPIs) each encoding a type III secretion system for virulence proteins. SPI1 is required for invasion, while systemic infections and intracellular accumulation of Salmonella are dependent on SPI2 function. This review will describe and compare the genetic organisation, evolution, regulation and molecular functions of SPI1 and SPI2.