Publications by authors named "Jörg Hacker"

103 Publications

Aboriginal artefacts on the continental shelf reveal ancient drowned cultural landscapes in northwest Australia.

PLoS One 2020 1;15(7):e0233912. Epub 2020 Jul 1.

College of Humanities, Arts and Social Sciences, Flinders University, Adelaide, Australia.

This article reports Australia's first confirmed ancient underwater archaeological sites from the continental shelf, located off the Murujuga coastline in north-western Australia. Details on two underwater sites are reported: Cape Bruguieres, comprising > 260 recorded lithic artefacts at depths down to -2.4 m below sea level, and Flying Foam Passage where the find spot is associated with a submerged freshwater spring at -14 m. The sites were discovered through a purposeful research strategy designed to identify underwater targets, using an iterative process incorporating a variety of aerial and underwater remote sensing techniques and diver investigation within a predictive framework to map the submerged landscape within a depth range of 0-20 m. The condition and context of the lithic artefacts are analysed in order to unravel their depositional and taphonomic history and to corroborate their in situ position on a pre-inundation land surface, taking account of known geomorphological and climatic processes including cyclone activity that could have caused displacement and transportation from adjacent coasts. Geomorphological data and radiometric dates establish the chronological limits of the sites and demonstrate that they cannot be later than 7000 cal BP and 8500 cal BP respectively, based on the dates when they were finally submerged by sea-level rise. Comparison of underwater and onshore lithic assemblages shows differences that are consistent with this chronological interpretation. This article sets a foundation for the research strategies and technologies needed to identify archaeological targets at greater depth on the Australian continental shelf and elsewhere, building on the results presented. Emphasis is also placed on the need for legislation to better protect and manage underwater cultural heritage on the 2 million square kilometres of drowned landscapes that were once available for occupation in Australia, and where a major part of its human history must lie waiting to be discovered.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233912PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329065PMC
September 2020

Addressing the Complex and Pressing Societal Issue of Air Pollution and Health.

Authors:
Jörg Hacker

Ann Glob Health 2019 12 16;85(1):142. Epub 2019 Dec 16.

German National Academy of Sciences Leopoldina, DE.

Air pollution is a pressing issue that needs to be addressed at all levels, more urgently than ever. Air pollution has been a recognized and serious health problem far longer than the beginning of industrialization. There are accounts from the Roman philosopher Seneca, who in a letter described some 2000 years ago how much better he felt after leaving "a ruinous mess of steam and soot".
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http://dx.doi.org/10.5334/aogh.2672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923779PMC
December 2019

Brexit and European science.

Science 2017 10;358(6361):279

Jörg Hacker is president of the German National Academy of Sciences Leopoldina. He has been working in the field of infection biology.

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http://dx.doi.org/10.1126/science.aaq1700DOI Listing
October 2017

A multidisciplinary approach to digital mapping of dinosaurian tracksites in the Lower Cretaceous (Valanginian-Barremian) Broome Sandstone of the Dampier Peninsula, Western Australia.

PeerJ 2017 21;5:e3013. Epub 2017 Mar 21.

School of Biological Sciences, The University of Queensland , Brisbane , Queensland , Australia.

The abundant dinosaurian tracksites of the Lower Cretaceous (Valanginian-Barremian) Broome Sandstone of the Dampier Peninsula, Western Australia, form an important part of the West Kimberley National Heritage Place. Previous attempts to document these tracksites using traditional mapping techniques (e.g., surface overlays, transects and gridlines combined with conventional photography) have been hindered by the non-trivial challenges associated with working in this area, including, but not limited to: (1) the remoteness of many of the tracksites; (2) the occurrence of the majority of the tracksites in the intertidal zone; (3) the size and complexity of many of the tracksites, with some extending over several square kilometres. Using the historically significant and well-known dinosaurian tracksites at Minyirr (Gantheaume Point), we show how these issues can be overcome through the use of an integrated array of remote sensing tools. A combination of high-resolution aerial photography with both manned and unmanned aircraft, airborne and handheld high-resolution lidar imaging and handheld photography enabled the collection of large amounts of digital data from which 3D models of the tracksites at varying resolutions were constructed. The acquired data encompasses a very broad scale, from the sub-millimetre level that details individual tracks, to the multiple-kilometre level, which encompasses discontinuous tracksite exposures and large swathes of coastline. The former are useful for detailed ichnological work, while the latter are being employed to better understand the stratigraphic and temporal relationship between tracksites in a broader geological and palaeoecological context. These approaches and the data they can generate now provide a means through which digital conservation and temporal monitoring of the Dampier Peninsula's dinosaurian tracksites can occur. As plans for the on-going management of the tracks in this area progress, analysis of the 3D data and 3D visualization will also likely provide an important means through which the broader public can experience these spectacular National Heritage listed landscapes.
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http://dx.doi.org/10.7717/peerj.3013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363262PMC
March 2017

Human mesenchymal stem cells: New sojourn of bacterial pathogens.

Int J Med Microbiol 2015 May 13;305(3):322-6. Epub 2015 Jan 13.

Kusuma School of Biological Sciences, Indian Institute of Technology, Hauz Khas, New Delhi 110067, India; Dr Reddy's Institute of Life Sciences, University of Hyderabad Campus, Professor C.R. Rao Road, Gachibowli, Hyderabad 500046, India. Electronic address:

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is the leading infectious disease which claims one human life every 15-20s globally. The persistence of this deadly disease in human population can be attributed to the ability of the bacterium to stay in latent form. M. tuberculosis possesses a plethora of mechanisms not only to survive latently under harsh conditions inside the host but also modulate the host immune cells in its favour. Various M. tuberculosis gene families have also been described to play a role in this process. Recently, human bone marrow derived mesenchymal stem cells (MSCs) have been reported as a niche for dormant M. tuberculosis. MSCs possess abilities to alter the host immune response. The bacterium finds this self-renewal and immune privileged nature of MSCs very favourable not only to modulate the host immune system, with some help from its own genes, but also to avoid the external drug pressure. We suggest that the MSCs not only provide a resting place for M. tuberculosis but could also, by virtue of their intrinsic ability to disseminate in the body, explain the genesis of extra-pulmonary TB. A similar exploitation of stem cells by other bacterial pathogens is a distinct possibility. It may be likely that other intracellular bacterial pathogens adopt this strategy to 'piggy-back' on to ovarian stem cells to ensure vertical transmission and successful propagation to the next generation.
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http://dx.doi.org/10.1016/j.ijmm.2015.01.001DOI Listing
May 2015

Genomic avenue to avian colisepticemia.

mBio 2015 Jan 13;6(1). Epub 2015 Jan 13.

Institute of Hygiene, Westfälische Wilhelms-Universität Münster, Münster, Germany

Unlabelled: Here we present an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78 that represent the major cause of avian colisepticemia, an invasive infection caused by avian pathogenic Escherichia coli (APEC) strains. It is associated with high mortality and morbidity, resulting in significant economic consequences for the poultry industry. To understand the genetic basis of the virulence of avian septicemic E. coli, we sequenced the entire genome of a clinical isolate of serotype O78-O78:H19 ST88 isolate 789 (O78-9)-and compared it with three publicly available APEC O78 sequences and one complete genome of APEC serotype O1 strain. Although there was a large variability in genome content between the APEC strains, several genes were conserved, which are potentially critical for colisepticemia. Some of these genes are present in multiple copies per genome or code for gene products with overlapping function, signifying their importance. A systematic deletion of each of these virulence-related genes identified three systems that are conserved in all septicemic strains examined and are critical for serum survival, a prerequisite for septicemia. These are the plasmid-encoded protein, the defective ETT2 (E. coli type 3 secretion system 2) type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the only APEC O78 strain that also carried the regulon coding for yersiniabactin, the iron binding system of the Yersinia high-pathogenicity island. Interestingly, this system is the only one that cannot be complemented by other iron uptake systems under iron limitation and in serum.

Importance: Avian colisepticemia is a severe systemic disease of birds causing high morbidity and mortality and resulting in severe economic losses. The bacteria associated with avian colisepticemia are highly antibiotic resistant, making antibiotic treatment ineffective, and there is no effective vaccine due to the multitude of serotypes involved. To understand the disease and work out strategies to combat it, we performed an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78, the major cause of the disease. We identified several potential virulence factors, conserved in all the colisepticemic strains examined, and determined their contribution to growth in serum, an absolute requirement for septicemia. These findings raise the possibility that specific vaccines or drugs can be developed against these critical virulence factors to help combat this economically important disease.
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http://dx.doi.org/10.1128/mBio.01681-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313913PMC
January 2015

Fire in Australian savannas: from leaf to landscape.

Glob Chang Biol 2015 Jan 9;21(1):62-81. Epub 2014 Sep 9.

School of Earth and Environment, The University of Western Australia, Crawley, WA, 6009, Australia; School of Geography and Environmental Science, Monash University, Melbourne, Vic., 3800, Australia.

Savanna ecosystems comprise 22% of the global terrestrial surface and 25% of Australia (almost 1.9 million km2) and provide significant ecosystem services through carbon and water cycles and the maintenance of biodiversity. The current structure, composition and distribution of Australian savannas have coevolved with fire, yet remain driven by the dynamic constraints of their bioclimatic niche. Fire in Australian savannas influences both the biophysical and biogeochemical processes at multiple scales from leaf to landscape. Here, we present the latest emission estimates from Australian savanna biomass burning and their contribution to global greenhouse gas budgets. We then review our understanding of the impacts of fire on ecosystem function and local surface water and heat balances, which in turn influence regional climate. We show how savanna fires are coupled to the global climate through the carbon cycle and fire regimes. We present new research that climate change is likely to alter the structure and function of savannas through shifts in moisture availability and increases in atmospheric carbon dioxide, in turn altering fire regimes with further feedbacks to climate. We explore opportunities to reduce net greenhouse gas emissions from savanna ecosystems through changes in savanna fire management.
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http://dx.doi.org/10.1111/gcb.12686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310295PMC
January 2015

[Science and society. Guidelines for the Leopoldina Study Center].

Authors:
Jörg Hacker

Acta Hist Leopoldina 2014 (66):9-17

In order to adequately perform its many diverse tasks as a scholars' society and as the German National Academy of Sciences, the Deutsche Akademie der Naturforscher Leopoldina needs to view itself in a historical context. This can only happen as part of a culture of remembrance which fosters the memory of the Leopoldina's past and subjects this to a critical analysis in the context of the history of science and academies. The newly founded Leopoldina Study Center for the History of Science and Science Academies is to be a forum that pursues established forms of historical research at the Leopoldina, organizes new scientific projects, and presents its findings to the public. The aim is to involve as many Leopoldina members as possible from all of its disciplines, as well as to collaborate with national and international partners.
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September 2014

[Welcoming address].

Authors:
Jörg Hacker

Acta Hist Leopoldina 2014 (63):7-9

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September 2014

E. coli as an all-rounder: the thin line between commensalism and pathogenicity.

Curr Top Microbiol Immunol 2013 ;358:3-32

Institute of Hygiene, University of Münster, Münster, Germany.

Escherichia coli is a paradigm for a versatile bacterial species which comprises harmless commensal as well as different pathogenic variants with the ability to either cause intestinal or extraintestinal diseases in humans and many animal hosts. Because of this broad spectrum of lifestyles and phenotypes, E. coli is a well-suited model organism to study bacterial evolution and adaptation to different growth conditions and niches. The geno- and phenotypic diversity, however, also hampers risk assessment and strain typing. A marked genome plasticity is the key to the great variability seen in this species. Acquisition of genetic information by horizontal gene transfer, gene loss as well as other genomic modifications, like DNA rearrangements and point mutations, can constantly alter the genome content and thus the fitness and competitiveness of individual variants in certain niches. Specific gene subsets and traits have been correlated with an increased potential of E. coli strains to cause intestinal or extraintestinal disease. Intestinal pathogenic E. coli strains can be reliably discriminated from non-pathogenic, commensal, or from extraintestinal E. coli pathogens based on genome content and phenotypic traits. An unambiguous distinction of extraintestinal pathogenic E. coli and commensals is, nevertheless, not so easy, as strains with the ability to cause extraintestinal infection are facultative pathogens and belong to the normal flora of many healthy individuals. Here, we compare insights into phylogeny, geno-, and phenotypic traits of commensal and pathogenic E. coli. We demonstrate that the borderline between extraintestinal virulence and intestinal fitness can be blurred as improved adaptability and competitiveness may promote intestinal colonization as well as extraintestinal infection by E. coli.
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http://dx.doi.org/10.1007/82_2012_303DOI Listing
July 2013

Comparison of asymptomatic bacteriuria Escherichia coli isolates from healthy individuals versus those from hospital patients shows that long-term bladder colonization selects for attenuated virulence phenotypes.

Infect Immun 2012 Feb 21;80(2):668-78. Epub 2011 Nov 21.

Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Würzburg, Germany.

Asymptomatic bacteriuria (ABU) is a condition where bacteria stably colonize the urinary tract, in a manner closely resembling commensalism at other mucosal sites. The patients carry >10(5) CFU/ml for extended periods of time and rarely develop symptoms. Contrasting the properties of ABU strains to those of uropathogenic isolates causing symptomatic infection is therefore highly relevant to understand mechanisms of bacterial adaptation. The prototype ABU strain Escherichia coli 83972 has a smaller genome than uropathogenic E. coli (UPEC) strains with deletions or point mutations in several virulence genes, suggesting that ABU strains undergo a programmed reductive evolution within human hosts. This study addressed if these observations can be generalized. Strains causing ABU in outpatients or hospitalized patients after catheterization or other invasive procedures were compared to commensal E. coli isolates from the intestinal flora of healthy individuals. Notably, clonal complex 73 (CC73) was a prominent phylogenetic lineage dominated by ABU isolates. ABU isolates from outpatients and hospitalized patients had a similar overall virulence gene repertoire, which distinguished them from many commensals, but typical UPEC virulence genes were less frequently attenuated in hospital strains than in outpatient strains or commensals. The decreased virulence potential of outpatient ABU isolates relative to that of ABU strains from hospitalized patients supports the hypothesis that loss of expression or decay of virulence genes facilitates long-term carriage and adaptation to host environments.
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http://dx.doi.org/10.1128/IAI.06191-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264318PMC
February 2012

DNA sequence analysis of the composite plasmid pTC conferring virulence and antimicrobial resistance for porcine enterotoxigenic Escherichia coli.

Int J Med Microbiol 2012 Jan 13;302(1):4-9. Epub 2011 Oct 13.

Veterinary Medical Research Institute of the Hungarian Academy of Sciences, Budapest, Hungary.

In this study the plasmid pTC, a 90 kb self-conjugative virulence plasmid of the porcine enterotoxigenic Escherichia coli (ETEC) strain EC2173 encoding the STa and STb heat-stable enterotoxins and tetracycline resistance, has been sequenced in two steps. As a result we identified five main distinct regions of pTC: (i) the maintenance region responsible for the extreme stability of the plasmid, (ii) the TSL (toxin-specific locus comprising the estA and estB genes) which is unique and characteristic for pTC, (iii) a Tn10 transposon, encoding tetracycline resistance, (iv) the tra (plasmid transfer) region, and (v) the colE1-like origin of replication. It is concluded that pTC is a self-transmissible composite plasmid harbouring antibiotic resistance and virulence genes. pTC belongs to a group of large conjugative E. coli plasmids represented by NR1 with a widespread tra backbone which might have evolved from a common ancestor. This is the first report of a completely sequenced animal ETEC virulence plasmid containing an antimicrobial resistance locus, thereby representing a selection advantage for spread of pathogenicity in the presence of antimicrobials leading to increased disease potential.
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http://dx.doi.org/10.1016/j.ijmm.2011.07.003DOI Listing
January 2012

Climate change and infectious diseases--impact of global warming and climate change on infectious diseases: myth or reality?

Int J Med Microbiol 2012 Jan 14;302(1):1-3. Epub 2011 Oct 14.

Institute of Life Sciences, University of Hyderabad, Hyderabad, India.

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http://dx.doi.org/10.1016/j.ijmm.2011.09.011DOI Listing
January 2012

Mobilisation and remobilisation of a large archetypal pathogenicity island of uropathogenic Escherichia coli in vitro support the role of conjugation for horizontal transfer of genomic islands.

BMC Microbiol 2011 Sep 24;11:210. Epub 2011 Sep 24.

Institute for Molecular Infection Biology, University of Würzburg, Josef-Schneider-Str, 2/Building D15, Würzburg, 97070, Germany.

Background: A substantial amount of data has been accumulated supporting the important role of genomic islands (GEIs)--including pathogenicity islands (PAIs)--in bacterial genome plasticity and the evolution of bacterial pathogens. Their instability and the high level sequence similarity of different (partial) islands suggest an exchange of PAIs between strains of the same or even different bacterial species by horizontal gene transfer (HGT). Transfer events of archetypal large genomic islands of enterobacteria which often lack genes required for mobilisation or transfer have been rarely investigated so far.

Results: To study mobilisation of such large genomic regions in prototypic uropathogenic E. coli (UPEC) strain 536, PAI II536 was supplemented with the mobRP4 region, an origin of replication (oriVR6K), an origin of transfer (oriTRP4) and a chloramphenicol resistance selection marker. In the presence of helper plasmid RP4, conjugative transfer of the 107-kb PAI II536 construct occured from strain 536 into an E. coli K-12 recipient. In transconjugants, PAI II536 existed either as a cytoplasmic circular intermediate (CI) or integrated site-specifically into the recipient's chromosome at the leuX tRNA gene. This locus is the chromosomal integration site of PAI II536 in UPEC strain 536. From the E. coli K-12 recipient, the chromosomal PAI II536 construct as well as the CIs could be successfully remobilised and inserted into leuX in a PAI II536 deletion mutant of E. coli 536.

Conclusions: Our results corroborate that mobilisation and conjugal transfer may contribute to evolution of bacterial pathogens through horizontal transfer of large chromosomal regions such as PAIs. Stabilisation of these mobile genetic elements in the bacterial chromosome result from selective loss of mobilisation and transfer functions of genomic islands.
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http://dx.doi.org/10.1186/1471-2180-11-210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202238PMC
September 2011

Collagen IV-derived peptide binds hydrophobic cavity of Legionella pneumophila Mip and interferes with bacterial epithelial transmigration.

Cell Microbiol 2011 Oct 28;13(10):1558-72. Epub 2011 Jul 28.

Institut für Mikrobiologie, Technische Universität Braunschweig, 38106 Braunschweig, Germany.

The Legionella virulence factor Mip (macrophage infectivity potentiator) contributes to bacterial dissemination within infected lung tissue. The Mip protein, which belongs to the enzyme family of FK506-binding proteins (FKBP), binds specifically to collagen IV. We identified a surface-exposed Mip-binding sequence in the NC1 domain of human collagen IV α1. The corresponding collagen IV-derived peptide (P290) co-precipitated with Mip and competitively inhibited the Mip-collagen IV binding. Transmigration of Legionella pneumophila across a barrier of NCI-H292 lung epithelial cells and extracellular matrix was efficiently inhibited by P290. This significantly reduced transmigration was comparable to the inefficient transmigration of PPIase-negative Mip mutant or rapamycin-treated L. pneumophila. Based on NMR data and docking studies a model for the mode of interaction of P290 and Mip was developed. The amino acids of the hydrophobic cavity of Mip, D142 and to a lesser extent Y185 were identified to be part of the interaction surface. In the complex structure of Mip(77-213) and P290, both amino acid residues form hydrogen bonds to P290. Utilizing modelling, molecular dynamics (MD) simulations and structural data of human PPIase FKBP12, the most related human orthologue of Mip, we were able to propose optimized P290 variants with increased binding specificity and selectivity for the putative bacterial drug target Mip.
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http://dx.doi.org/10.1111/j.1462-5822.2011.01641.xDOI Listing
October 2011

High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis.

BMC Genomics 2010 Oct 21;11:591. Epub 2010 Oct 21.

University of Würzburg, Institute for Molecular Infection Biology, Würzburg, Germany.

Background: The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens.

Results: We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes.

Conclusions: Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.
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http://dx.doi.org/10.1186/1471-2164-11-591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017858PMC
October 2010

Host imprints on bacterial genomes--rapid, divergent evolution in individual patients.

PLoS Pathog 2010 Aug 26;6(8):e1001078. Epub 2010 Aug 26.

Institute for Molecular Biology of Infectious Diseases, Julius-Maximilians-University Würzburg, Würzburg, Germany.

Bacteria lose or gain genetic material and through selection, new variants become fixed in the population. Here we provide the first, genome-wide example of a single bacterial strain's evolution in different deliberately colonized patients and the surprising insight that hosts appear to personalize their microflora. By first obtaining the complete genome sequence of the prototype asymptomatic bacteriuria strain E. coli 83972 and then resequencing its descendants after therapeutic bladder colonization of different patients, we identified 34 mutations, which affected metabolic and virulence-related genes. Further transcriptome and proteome analysis proved that these genome changes altered bacterial gene expression resulting in unique adaptation patterns in each patient. Our results provide evidence that, in addition to stochastic events, adaptive bacterial evolution is driven by individual host environments. Ongoing loss of gene function supports the hypothesis that evolution towards commensalism rather than virulence is favored during asymptomatic bladder colonization.
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http://dx.doi.org/10.1371/journal.ppat.1001078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928814PMC
August 2010

Nosocomial infections and their control.

Int J Med Microbiol 2010 Aug 31;300(6):341. Epub 2010 Jul 31.

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http://dx.doi.org/10.1016/j.ijmm.2010.07.001DOI Listing
August 2010

Mat fimbriae promote biofilm formation by meningitis-associated Escherichia coli.

Microbiology (Reading) 2010 Aug 3;156(Pt 8):2408-2417. Epub 2010 Jun 3.

General Microbiology, Department of Biosciences, FI-00014 University of Helsinki, Finland.

The mat (or ecp) fimbrial operon is ubiquitous and conserved in Escherichia coli, but its functions remain poorly described. In routine growth media newborn meningitis isolates of E. coli express the meningitis-associated and temperature-regulated (Mat) fimbria, also termed E. coli common pilus (ECP), at 20 degrees C, and here we show that the six-gene (matABCDEF)-encoded Mat fimbria is needed for temperature-dependent biofilm formation on abiotic surfaces. The matBCDEF deletion mutant of meningitis E. coli IHE 3034 was defective in an early stage of biofilm development and consequently unable to establish a detectable biofilm, contrasting with IHE 3034 derivatives deleted for flagella, type 1 fimbriae or S-fimbriae, which retained the wild-type biofilm phenotype. Furthermore, induced production of Mat fimbriae from expression plasmids enabled biofilm-deficient E. coli K-12 cells to form biofilm at 20 degrees C. No biofilm was detected with IHE 3034 or MG1655 strains grown at 37 degrees C. The surface expression of Mat fimbriae and the frequency of Mat-positive cells in the IHE 3034 population from 20 degrees C were high and remained unaltered during the transition from planktonic to biofilm growth and within the matured biofilm community. Considering the prevalence of the highly conserved mat locus in E. coli genomes, we hypothesize that Mat fimbria-mediated biofilm formation is an ancestral characteristic of E. coli.
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http://dx.doi.org/10.1099/mic.0.039610-0DOI Listing
August 2010

Pathogenomic comparison of human extraintestinal and avian pathogenic Escherichia coli--search for factors involved in host specificity or zoonotic potential.

Microb Pathog 2010 Sep 12;49(3):105-15. Epub 2010 May 12.

Institut für Molekulare Infektionsbiologie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.

Avian pathogenic Escherichia coli (APEC) and human extraintestinal pathogenic E. coli (ExPEC) cause various diseases in humans and animals and cannot be clearly distinguished by molecular epidemiology and genome content. We characterized traits of eight representative human ExPEC and APEC variants to either support the zoonotic potential or indicate factors involved in host specificity. These strains were very similar regarding phylogeny, virulence gene content and allelic variation of adhesins. Host- or serogroup-specific differences in type 1-, P-, S/F1C-fimbriae, curli, flagella, colicin and aerobactin expression or in vivo virulence were not found. Serogroup-dependent differences in genome content may depend on the phylogenetic background. To identify traits involved in host specificity, we performed transcriptome analysis of human ExPEC IHE3034 and APEC BEN374 in response to human (37 degrees C) or avian (41 degrees C) body temperature. Both isolates displayed similar transcriptional profiles at both temperatures. Transcript levels of motility/chemotaxis genes were repressed at 41 degrees C. The hdeAB and cadA genes involved in acid stress resistance, although often induced at 41 degrees C, could not be correlated with host specificity. Beside strain-specific effects, the common behavior of both strains at human or avian body temperature supports the idea of a potential zoonotic risk of certain human ExPEC and APEC variants.
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http://dx.doi.org/10.1016/j.micpath.2010.05.004DOI Listing
September 2010

Bacterial genome plasticity and its impact on adaptation during persistent infection.

Int J Med Microbiol 2010 Aug 7;300(6):363-6. Epub 2010 May 7.

Julius-Maximilians-Universität Würzburg, Institut für Molekulare Infektionsbiologie, Josef-Schneider-Str. 2/Bau D15, 97080 Würzburg, Germany.

Bacterial pathogens with the ability to cause persistent infection have different strategies to withstand the induction of host immune responses and to successfully establish long-term colonization. In case of asymptomatic bacteriuria and other persistent infections, prolonged growth in the host is accompanied with genomic alterations that result in e.g., bacterial attenuation thus contributing to bacterial adaptation to their host niche and a reduced activation of host immune responses. The accumulating amount of information regarding bacterial adaptation during persistent infection helps to increase our understanding of driving forces of bacterial adaptation in vivo as well as of factors that contribute to symptomatic infection.
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http://dx.doi.org/10.1016/j.ijmm.2010.04.010DOI Listing
August 2010

Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli.

Proc Natl Acad Sci U S A 2010 May 3;107(20):9072-7. Epub 2010 May 3.

Novartis Vaccines and Diagnostics, 53100 Siena, Italy.

Extraintestinal pathogenic Escherichia coli (ExPEC) are a common cause of disease in both mammals and birds. A vaccine to prevent such infections would be desirable given the increasing antibiotic resistance of these bacteria. We have determined the genome sequence of ExPEC IHE3034 (ST95) isolated from a case of neonatal meningitis and compared this to available genome sequences of other ExPEC strains and a few nonpathogenic E. coli. We found 19 genomic islands present in the genome of IHE3034, which are absent in the nonpathogenic E. coli isolates. By using subtractive reverse vaccinology we identified 230 antigens present in ExPEC but absent (or present with low similarity) in nonpathogenic strains. Nine antigens were protective in a mouse challenge model. Some of them were also present in other pathogenic non-ExPEC strains, suggesting that a broadly protective E. coli vaccine may be possible. The gene encoding the most protective antigen was detected in most of the E. coli isolates, highly conserved in sequence and found to be exported by a type II secretion system which seems to be nonfunctional in nonpathogenic strains.
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http://dx.doi.org/10.1073/pnas.0915077107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889118PMC
May 2010

Differential effects and interactions of endogenous and horizontally acquired H-NS-like proteins in pathogenic Escherichia coli.

Mol Microbiol 2010 Jan 4;75(2):280-93. Epub 2009 Dec 4.

Department of Molecular Biology, The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Umeå, Sweden.

The nucleoid-associated protein H-NS is important for gene regulation in Escherichia coli. We have studied H-NS interaction with StpA and an uncharacterized H-NS-like protein, Hfp, in the uropathogenic E. coli isolate 536 that expresses all three nucleoid-associated proteins. We found distinct interactions of the three proteins at the protein level, resulting in the formation of heteromers, as well as differences in their gene expression at the transcriptional level. Mutants lacking either StpA or Hfp alone did not exhibit a phenotype at 37 degrees C, which is consistent with a low level of expression at that temperature. Expression of the hfp and stpA genes was found to be induced by apparently diametrical conditions, and StpA and Hfp levels could be correlated to modulatory effects on the expression of different H-NS targets, the bgl operon and operons for virulence factors such as fimbriae and capsular polysaccharide. The hns/hfp and hns/stpA double mutants displayed severe growth defects at low and high temperatures respectively. Our findings demonstrated different requirements for the alternative H-NS/Hfp/StpA combinations under these growth conditions. We propose that Hfp and StpA have distinct functions and roles in a dynamic pool of nucleoid-associated proteins that is adapting to requirements in a particular environment.
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http://dx.doi.org/10.1111/j.1365-2958.2009.06995.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814080PMC
January 2010

Control of flagellar gene regulation in Legionella pneumophila and its relation to growth phase.

J Bacteriol 2010 Jan 13;192(2):446-55. Epub 2009 Nov 13.

Institut Pasteur, Biologie des Bactéries Intracellulaires, 75724 Paris Cedex 15, France.

The bacterial pathogen Legionella pneumophila responds to environmental changes by differentiation. At least two forms are well described: replicative bacteria are avirulent; in contrast, transmissive bacteria express virulence traits and flagella. Phenotypic analysis, Western blotting, and electron microscopy of mutants of the regulatory genes encoding RpoN, FleQ, FleR, and FliA demonstrated that flagellin expression is strongly repressed and that the mutants are nonflagellated in the transmissive phase. Transcriptome analyses elucidated that RpoN, together with FleQ, enhances transcription of 14 out of 31 flagellar class II genes, which code for the basal body, hook, and regulatory proteins. Unexpectedly, FleQ independent of RpoN enhances the transcription of fliA encoding sigma 28. Expression analysis of a fliA mutant showed that FliA activates three out of the five remaining flagellar class III genes and the flagellar class IV genes. Surprisingly, FleR does not induce but inhibits expression of at least 14 flagellar class III genes on the transcriptional level. Thus, we propose that flagellar class II genes are controlled by FleQ and RpoN, whereas the transcription of the class III gene fliA is controlled in a FleQ-dependent but RpoN-independent manner. However, RpoN and FleR might influence flagellin synthesis on a posttranscriptional level. In contrast to the commonly accepted view that enhancer-binding proteins such as FleQ always interact with RpoN to fullfill their regulatory functions, our results strongly indicate that FleQ regulates gene expression that is RpoN dependent and RpoN independent. Finally, FliA induces expression of flagellar class III and IV genes leading to the complete synthesis of the flagellum.
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http://dx.doi.org/10.1128/JB.00610-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805308PMC
January 2010

Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae.

Infect Immun 2009 Nov 31;77(11):4696-703. Epub 2009 Aug 31.

Julius-Maximilians-Universität Würzburg, Institut für Molekulare Infektionsbiologie, Röntgenring 11, D-97070 Würzburg, Germany.

A genomic island encoding the biosynthesis and secretion pathway of putative hybrid nonribosomal peptide-polyketide colibactin has been recently described in Escherichia coli. Colibactin acts as a cyclomodulin and blocks the eukaryotic cell cycle. The origin and prevalence of the colibactin island among enterobacteria are unknown. We therefore screened 1,565 isolates of different genera and species related to the Enterobacteriaceae by PCR for the presence of this DNA element. The island was detected not only in E. coli but also in Klebsiella pneumoniae, Enterobacter aerogenes, and Citrobacter koseri isolates. It was highly conserved among these species and was always associated with the yersiniabactin determinant. Structural variations between individual strains were only observed in an intergenic region containing variable numbers of tandem repeats. In E. coli, the colibactin island was usually restricted to isolates of phylogenetic group B2 and inserted at the asnW tRNA locus. Interestingly, in K. pneumoniae, E. aerogenes, C. koseri, and three E. coli strains of phylogenetic group B1, the functional colibactin determinant was associated with a genetic element similar to the integrative and conjugative elements ICEEc1 and ICEKp1 and to several enterobacterial plasmids. Different asn tRNA genes served as chromosomal insertion sites of the ICE-associated colibactin determinant: asnU in the three E. coli strains of ECOR group B1, and different asn tRNA loci in K. pneumoniae. The detection of the colibactin genes associated with an ICE-like element in several enterobacteria provides new insights into the spread of this gene cluster and its putative mode of transfer. Our results shed light on the mechanisms of genetic exchange between members of the family Enterobacteriaceae.
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http://dx.doi.org/10.1128/IAI.00522-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772509PMC
November 2009

The SfaXII protein from newborn meningitis E. coli is involved in regulation of motility and type 1 fimbriae expression.

Microb Pathog 2009 May 4;46(5):243-52. Epub 2009 Feb 4.

Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden, Umeå University, S-90187 Umeå, Sweden.

The genomes of pathogenic Escherichia coli may contain several different fimbrial operons. How bacteria regulate and coordinate the choice of fimbrial expression under different circumstances remains largely unanswered. In this report we have investigated the role of the sfaX(II) gene associated to the Sfa(II) fimbrial determinant in the E. coli isolate IHE3034. sfaX(II) belongs to a subfamily of genes, the 17k Da genes, located near different fimbrial operons in uropathogenic and newborn meningitis E. coli (NMEC) strains. Using the NMEC isolate IHE3034 and non-pathogenic E. coli strains we found that the sfaX(II) gene had an inhibitory effect on type 1 fimbriae expression. Down-regulation of type 1 fimbriae was exerted at transcriptional level both by inhibiting expression from the fimA promoter and by reducing the frequency of OFF-to-ON switching. The effect of sfaX(II) on expression of the recombinase FimB that catalyzes OFF-to-ON switching might explain the described reduction in percentage of ON cells. Moreover, expression of the sfaX(II) gene strongly influenced motility and flagella production of the NMEC isolate IHE3034. We propose that the sfaX(II) gene, and presumably other members in the 17 kDa gene family, may play a role in the control of virulence related gene expression in pathogenic E. coli.
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http://dx.doi.org/10.1016/j.micpath.2009.01.007DOI Listing
May 2009

Cytolethal distending toxin type I and type IV genes are framed with lambdoid prophage genes in extraintestinal pathogenic Escherichia coli.

Infect Immun 2009 Jan 3;77(1):492-500. Epub 2008 Nov 3.

Veterinary Medical Research Institute of the Hungarian Academy of Sciences, Budapest, Hungary.

Five types of cytolethal distending toxin (CDT-I to CDT-V) have been identified in Escherichia coli. In the present study we cloned and sequenced the cdt-IV operon and flanking region from a porcine extraintestinal pathogenic E. coli (ExPEC) strain belonging to serogroup O75. We confirmed that similar to other CDTs, CDT-IV induced phosphorylation of host histone H2AX, a sensitive marker of DNA double-strand breaks, and blocked the HeLa cell cycle at the G(2)-M transition. The cdt-IV genes were framed by lambdoid prophage genes. We cloned and sequenced the cdt-I operon and flanking regions from a human ExPEC O18:K1:H7 strain and observed that cdt-I genes were also flanked by lambdoid prophage genes. PCR studies indicated that a gene coding for a putative protease was always associated with the cdtC-IV gene but was not associated with cdtC genes in strains producing CDT-I, CDT-III, and CDT-V. Our results suggest that the cdt-I and cdt-IV genes might have been acquired from a common ancestor by phage transduction and evolved in their bacterial hosts. The lysogenic bacteriophages have the potential to carry nonessential "cargo" genes or "morons" and therefore play a crucial role in the generation of genetic diversity within ExPEC.
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http://dx.doi.org/10.1128/IAI.00962-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612248PMC
January 2009