ACE news
> ACE Annual Meeting 23-25 April 2008> Kees Leenhouts and Maarten van Rosmalen have left Biomade.
Tjibbe Bosma is now Biomade's projectleader for the ACE project
ACE meetings
Participating institutes
A
Participant no 1 Co-ordinator
University Medical Centre Utrecht
Utrecht, The Netherlands
Phone: +31-30-250 7639
Fax: +31-30-254 1770
website
University Medical Centre Utrecht
Utrecht, The Netherlands
Phone: +31-30-250 7639
Fax: +31-30-254 1770
website
Description of the Institute
The UMCU is 1,200-bed university teaching hospital providing pediatric and adult care, with all medical specialties represented, located centrally in the Netherlands. The UMCU hosts the Eijkman Winkler Institute (EWI) for Microbiology and Infectious Diseases, where clinicians and basic researchers from the departments of Medical Microbiology, Infectious Diseases and Pediatrics collaborate. Central research themes of the EWI include, amongst others, antibiotic resistance and pathogenesis of bacterial infections. Antibiotic resistance has been a central research theme since 1976 and since then, numerous scientific publications addressing all aspects of this issue have been produced. Notably, the Dutch “search and destroy”, nowadays famous for controlling MRSA in Dutch hospitals, has been developed in the EWI in the early nineteen-eighties. All necessary equipment for the proposed studies is fully operational in our labs.
The UMCU is 1,200-bed university teaching hospital providing pediatric and adult care, with all medical specialties represented, located centrally in the Netherlands. The UMCU hosts the Eijkman Winkler Institute (EWI) for Microbiology and Infectious Diseases, where clinicians and basic researchers from the departments of Medical Microbiology, Infectious Diseases and Pediatrics collaborate. Central research themes of the EWI include, amongst others, antibiotic resistance and pathogenesis of bacterial infections. Antibiotic resistance has been a central research theme since 1976 and since then, numerous scientific publications addressing all aspects of this issue have been produced. Notably, the Dutch “search and destroy”, nowadays famous for controlling MRSA in Dutch hospitals, has been developed in the EWI in the early nineteen-eighties. All necessary equipment for the proposed studies is fully operational in our labs.
All participants of the UMCU-research group have a long-lasting experience in antibiotic resistance
research. The EWI hosts probably the largest and best defined collection of
E. faecium isolates from multiple epidemiological niches and all continents,
with isolation dates going back to the nineteen-fifties. Our group has developed
MLST-schemes for E. faecium and E. faecalis, as well as a
MLVA scheme for E. faecium (http://www.mlst.net;
http://www.mlva.umcutrecht.nl).
The E. faecium collection, and the MLST scheme, were used to define the population
structure and to identify the critical role of clonal complex-17 (CC-17) in
the epidemiology of the global nosocomial epidemic of VRE. As a matter of fact,
this expertise and collection will be unrestricted available for the proposed
research projects. In addition, several researchers have considerable experience
with experiments on horizontal gene transfer and bacterial genomics.
Prof dr. M. Bonten, Clinical Infectious Diseases, (Molecular) Epidemiology, Mathematical modeling
Dr. R. Willems, Molecular Epidemiology and microbiology
Dr. A. Fluit, Molecular Biology
Dr. W. van Schaik, Molecular Biology
A. Hendrickx, Molecular Biology
Dr. J. Top, Molecular Biology
M. Leendertse, Microbiology
H. Leavis, Clinical Infectious Diseases/ Molecular Biology
B
Dr. R. Willems, Molecular Epidemiology and microbiology
Dr. A. Fluit, Molecular Biology
Dr. W. van Schaik, Molecular Biology
A. Hendrickx, Molecular Biology
Dr. J. Top, Molecular Biology
M. Leendertse, Microbiology
H. Leavis, Clinical Infectious Diseases/ Molecular Biology
Participant no 2
Statens Serum Institute
Copenhagen, Denmark
Phone: +45 3268 3268
Fax: (+45) 32683231
website
Statens Serum Institute
Copenhagen, Denmark
Phone: +45 3268 3268
Fax: (+45) 32683231
website
Description of the Institute
Statens Serum Institut is a public enterprise operating as a market-oriented production and service enterprise.
Statens Serum Institut is an enterprise under the Danish Ministry of the Interior and Health, and the Institute’s duties are partly integrated in the national Danish health services.
Statens Serum Institut prevents and controls infectious diseases and congenital disorders.
The Statens Serum Insitute’s expertise includes:
• Monitoring, advising and teaching on the incidence, prevention and treatment of infectious diseases and congenital disorders.
• Specializing in the diagnosis of infectious, autoimmune, congenital and genetic diseases.
• Ensuring the supply of vaccines, other biological products and diagnostic services through production and procurement.
• Preparedness against biological terrorism.
• Research and development in the Institute's areas of activity at an international level.
Statens Serum Institut aims to ensure advanced control of infectious diseases, including new infections and biological threats. The Institute also strives to be a highly regarded and recognized national and international research, production and service enterprise.
Statens Serum Institut is a public enterprise operating as a market-oriented production and service enterprise.
Statens Serum Institut is an enterprise under the Danish Ministry of the Interior and Health, and the Institute’s duties are partly integrated in the national Danish health services.
Statens Serum Institut prevents and controls infectious diseases and congenital disorders.
The Statens Serum Insitute’s expertise includes:
• Monitoring, advising and teaching on the incidence, prevention and treatment of infectious diseases and congenital disorders.
• Specializing in the diagnosis of infectious, autoimmune, congenital and genetic diseases.
• Ensuring the supply of vaccines, other biological products and diagnostic services through production and procurement.
• Preparedness against biological terrorism.
• Research and development in the Institute's areas of activity at an international level.
Statens Serum Institut aims to ensure advanced control of infectious diseases, including new infections and biological threats. The Institute also strives to be a highly regarded and recognized national and international research, production and service enterprise.
The Statens Serum Institut (SSI) works as reference unit for the Danish clinical
laboratories according to resistant enterococci. SSI has experience in molecular
typing and characterization of antibiotic resistant and virulence genes of
enterococci. SSI has a surveillance of resistance in enterococci obtained
from non-hospitalized volunteers (normal flora study). The particular experience
of SSI is gene transfer studies in vivo both in mice and man.
Dr. A.M. Hammerum, Molecular genetics, gene transfer and normal flora
C. H. Lester, Molecular genetics, molecular epidemiology and animal models for gene transfer
C
C. H. Lester, Molecular genetics, molecular epidemiology and animal models for gene transfer
Participant no 3
Technical University of Denmark
Copenhagen, Denmark
Phone: +45 72 34 60 00
Fax: (+45) 72346001
website
Technical University of Denmark
Copenhagen, Denmark
Phone: +45 72 34 60 00
Fax: (+45) 72346001
website
Description of the Institute
Danish Institute for Food and Veterinary Research (DFVF) is the Danish reference laboratory for food safety, animal health and welfare. Antimicrobial resistance is one of the core areas at this institution (www.dfvf.dk). DFVF has a long tradition for research in antimicrobial resistance and is part of the Danish Integrated Antimicrobial Resistance Monitoring and Research Program (DANMAP) that monitors usage and prevalence of antimicrobial resistance in food animals, food and humans. Furthermore DFVF produced the scientific data for the Danish ban against usage of antimicrobial growth promoters that later was introduced in all of the European Union. DFVF is hosting a WHO Collaborating Centre for antimicrobial resistance in pathogens from foods and participates in the WHO Salmonella Survey. DFVF is part of the MedVetNet, an EU Network of Excellence for the integration of veterinary, medical and food scientists, in the field of food safety.
Section of Antimicrobial Resistance has published more than 100 articles on antimicrobial resistance in peer review journals and has been the driving force both national and international for prudent usage of antimicrobials in animal production. The head of the section Professor Frank M. Aarestrup and his colleagues received recently the APUA (Alliance for Prudent Use of Antibiotics) award for their research on the feasibility of food animal production without the use of antimicrobial growth promoters.
Danish Institute for Food and Veterinary Research (DFVF) is the Danish reference laboratory for food safety, animal health and welfare. Antimicrobial resistance is one of the core areas at this institution (www.dfvf.dk). DFVF has a long tradition for research in antimicrobial resistance and is part of the Danish Integrated Antimicrobial Resistance Monitoring and Research Program (DANMAP) that monitors usage and prevalence of antimicrobial resistance in food animals, food and humans. Furthermore DFVF produced the scientific data for the Danish ban against usage of antimicrobial growth promoters that later was introduced in all of the European Union. DFVF is hosting a WHO Collaborating Centre for antimicrobial resistance in pathogens from foods and participates in the WHO Salmonella Survey. DFVF is part of the MedVetNet, an EU Network of Excellence for the integration of veterinary, medical and food scientists, in the field of food safety.
Section of Antimicrobial Resistance has published more than 100 articles on antimicrobial resistance in peer review journals and has been the driving force both national and international for prudent usage of antimicrobials in animal production. The head of the section Professor Frank M. Aarestrup and his colleagues received recently the APUA (Alliance for Prudent Use of Antibiotics) award for their research on the feasibility of food animal production without the use of antimicrobial growth promoters.
The Danish Centre for Antimicrobial Resistance (DaCAR), Section of Antimicrobial
Resistance has for many years worked on characterization of antimicrobial resistance
by monitoring presence and prevalence among pathogenic and indicator (enterococci
and E. coli) bacteria in both national and international surveillance
systems. DaCAR has a large strains collection of enterococci isolated from food
animals and food products and by characterization of these isolates (PFGE typing)
and the genetic background for resistance been able to identify epidemiological
spread of antimicrobial resistance from farm to fork. PCR based detection of the
most prevalent antimicrobial resistance genes and virulence as well as PFGE typing
of isolates are routinely run in the lab. Work on characterization of the Tn1546
transposon encoding vancomycin resistance lead to a better understanding of dissemination
of vancomycin resistance. Of other focus areas for resistance mechanisms work,
macrolide (erm-genes) -, metal - and tetracycline resistance genes not
only in animals but also the environment should be mentioned. Recently focus has
been on the mobile DNA elements hosting the antimicrobial resistance genes and
a classification of enterococcal plasmids has been been suggested. Based on this
presence of the defined groups have been determined among enterococcal isolates
and new replicons from E. faecium plasmids has been cloned and characterized.
A multiplex PCR for species identification of enterococcal spp. has also been
designed and verified.
Prof. F. M. Aarestrup, Antimicrobial resistance surveillance, typing and genetic characterization of antimicrobial resistance.
Dr. L. B. Jensen, Genetic characterization of resistance genes and mobile DNA elements
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Dr. L. B. Jensen, Genetic characterization of resistance genes and mobile DNA elements
Description of the Institute
The Department of Microbiology and Virology (DMV) is located within the Institute of Medical Biology (IMB), Faculty of Medicine, University of Tromso. The DMV is devoted to research and higher education in medical microbiology and has a close collaboration with the Department of Clinical Microbiology at the University Hospital of North-Norway. The National Reference Centre for Antimicrobial Resistance (K-res) and the Norwegian Surveillance System for Antimicrobial Resistance (NORM) are located within our Departments. The particular research themes within the Bacteriology Research Group (BRG) at the DMV are the genetic basis and support of antimicrobial resistance in human bacterial pathogens, molecular epidemiology of antimicrobial resistance, horizontal gene transfer in bacteria, bacterial fitness, and bacterial genetics. We have also a close collaboration with the internationally well-known RNA biology research group at our institute in the development and application of ribozymal genetic knockdown techniques in Gram-positive bacteria.
The Department of Microbiology and Virology (DMV) is located within the Institute of Medical Biology (IMB), Faculty of Medicine, University of Tromso. The DMV is devoted to research and higher education in medical microbiology and has a close collaboration with the Department of Clinical Microbiology at the University Hospital of North-Norway. The National Reference Centre for Antimicrobial Resistance (K-res) and the Norwegian Surveillance System for Antimicrobial Resistance (NORM) are located within our Departments. The particular research themes within the Bacteriology Research Group (BRG) at the DMV are the genetic basis and support of antimicrobial resistance in human bacterial pathogens, molecular epidemiology of antimicrobial resistance, horizontal gene transfer in bacteria, bacterial fitness, and bacterial genetics. We have also a close collaboration with the internationally well-known RNA biology research group at our institute in the development and application of ribozymal genetic knockdown techniques in Gram-positive bacteria.
The BRG has 10 years of experience in the field of antimicrobial resistance in
general and in particular in Gram-positive bacteria (enterococci, staphylococci
and streptococci). Our expertise has been acknowledged at the national level by
the location of two national reference functions in our laboratories (K-res and
NORM; see paragraph 1). We have a large national and international network through
ongoing antimicrobial research and surveillance.
Specific existing techniques include: phenotypic and genetic detection of antimicrobial resistance, gene transfer techniques in vitro (filter mating) and in vivo (gnotobiotic mice in collaboration with external resources), BAC and cosmid library construction, cloning and analysis of mobile genetic elements, plasmid DNA sequence analysis, real-time and inverse PCR, pulsed-field gel electrophoresis, multi-locus sequence typing, bacterial fitness analysis, development of Rnase P-based knockdown of gene expression in Gram-positive bacteria.
Specific existing techniques include: phenotypic and genetic detection of antimicrobial resistance, gene transfer techniques in vitro (filter mating) and in vivo (gnotobiotic mice in collaboration with external resources), BAC and cosmid library construction, cloning and analysis of mobile genetic elements, plasmid DNA sequence analysis, real-time and inverse PCR, pulsed-field gel electrophoresis, multi-locus sequence typing, bacterial fitness analysis, development of Rnase P-based knockdown of gene expression in Gram-positive bacteria.
Prof. A. Sundsfjord, Project management, molecular epidemiology of antimicrobial resistance, molecular bacteriology
Dr. K H Dahl, Molecular bacteriology and techniques, bacterial gene transfer
Dr. J E Sollid, Molecular bacteriology and techniques
Dr. G S Simonsen, Molecular epidemiology and surveillance of antimicrobial resistance
Prof. dr. S Johansen, Ribozymes: functional analysis and application
A Hanssen, Molecular bacteriology and techniques, bacterial gene transfer
T Tessem, Technical assistance
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Dr. K H Dahl, Molecular bacteriology and techniques, bacterial gene transfer
Dr. J E Sollid, Molecular bacteriology and techniques
Dr. G S Simonsen, Molecular epidemiology and surveillance of antimicrobial resistance
Prof. dr. S Johansen, Ribozymes: functional analysis and application
A Hanssen, Molecular bacteriology and techniques, bacterial gene transfer
T Tessem, Technical assistance
Participant no 5
Norwegian University of Life Sciences
Aas, Norway
Phone: + 47 64 96 50 00
Fax: (+47) 64941465
website
Norwegian University of Life Sciences
Aas, Norway
Phone: + 47 64 96 50 00
Fax: (+47) 64941465
website
Description of the Institute
For years the Laboratory of Microbial Gene Technology research group of the Department of Chemistry, Biotechnology and Food Science has been working with antimicrobial peptides, and lactic acid bacteria (LAB), including enterococci. This research group believes that the antimicrobial potential of intestinal bacteria protect the GI tract from being infected by pathogenic bacteria. During the last couple of years UMB established DNA microarray technology on bacterial genomes that includes arrays on enterococci and staphylococci. The Norwegian University of Life Sciences (UMB) has a strong expertise at our department and in our group on biostatistics and bioinformatics, and molecular technologies.
For years the Laboratory of Microbial Gene Technology research group of the Department of Chemistry, Biotechnology and Food Science has been working with antimicrobial peptides, and lactic acid bacteria (LAB), including enterococci. This research group believes that the antimicrobial potential of intestinal bacteria protect the GI tract from being infected by pathogenic bacteria. During the last couple of years UMB established DNA microarray technology on bacterial genomes that includes arrays on enterococci and staphylococci. The Norwegian University of Life Sciences (UMB) has a strong expertise at our department and in our group on biostatistics and bioinformatics, and molecular technologies.
This group is currently researching the diversity of enterococci in breast-fed babies and their ability to produce antibacterial peptides. This research group also has a focus on gene diversity between enterococci from different environments. For years this research group has studied temperate phages/prophages in LAB and is presently studying how such phage genomes spread and diversify bacterial genomes. This is an important aspect of dissemination of virulence and antibiotic resistance amongst bacteria
The major working tool in this project will be DNA microarray technology including
the bioinformatics. Presently a PCR based DNA array of 3160 genes of E. faecalis
V583 is available at UMB and will at the end of this year have an extended oligo-based
array of the same organism. In addition UMB has a PCR based DNA microarray of
E. faecium DO with 2136 genes. The work of UMB will focus on the genetic
diversity in enterococci based on comparative genome hybridization (CGH) in order
to identify potential virulence genes and their mobility within the Enterococcus
species. By studying using isolates from different environments, such as hospital
and patients, food, GI tract from adults and babies, animals etc. it should be
possible to identify genes that more prevalent or dominating in the various environments.
Transcriptional studies will also be included in the project in order to evaluate differences in transcriptional strength between strains at different growth conditions. Also the mobility of antibiotic resistant genes will be studied. The involvement of prophage elements in the mobility of such traits will also be researched by UMB. UMB has a DNA transformation procedure available which will be used to make gene knock-out mutants in E. faecalis which have been established in this group. These technologies will be important in studying virulence genes.
Transcriptional studies will also be included in the project in order to evaluate differences in transcriptional strength between strains at different growth conditions. Also the mobility of antibiotic resistant genes will be studied. The involvement of prophage elements in the mobility of such traits will also be researched by UMB. UMB has a DNA transformation procedure available which will be used to make gene knock-out mutants in E. faecalis which have been established in this group. These technologies will be important in studying virulence genes.
Prof. dr. I F Nes, Group leader
Dr. A Aakra, DNA microarray technology
H Vebø, DNA microarray, antibiotic stress on enterococci
L Godager, DNA techniques
Dr. L Snipen, Bioinformatics
F
Dr. A Aakra, DNA microarray technology
H Vebø, DNA microarray, antibiotic stress on enterococci
L Godager, DNA techniques
Dr. L Snipen, Bioinformatics
Participant no 6
Universitätsklinikum Freiburg für die Medizinische Fakultät der Albert-Ludwigs-Universität
Freiburg, Germany
Phone: (+49) 7612701828
Fax: (+49) 7612701820
website
Universitätsklinikum Freiburg für die Medizinische Fakultät der Albert-Ludwigs-Universität
Freiburg, Germany
Phone: (+49) 7612701828
Fax: (+49) 7612701820
website
Description of the Institute
The Division of Infectious Diseases at the University Hospital Freiburg is responsible for the infectious disease consult service at the University Hospital, a large 2000-bed tertiary care center in the south of Germany. Six physicians and 13 scientists and technicians work in four research groups on topics such bacterial pathogenesis, antibiotic resistance mechanisms, and antibiotic consumption. Dr. Huebner is Director of the Infectious Disease Research Laboratory at the Division of Infectious Diseases, Department of Medicine at the University Hospital Freiburg.
The Division of Infectious Diseases at the University Hospital Freiburg is responsible for the infectious disease consult service at the University Hospital, a large 2000-bed tertiary care center in the south of Germany. Six physicians and 13 scientists and technicians work in four research groups on topics such bacterial pathogenesis, antibiotic resistance mechanisms, and antibiotic consumption. Dr. Huebner is Director of the Infectious Disease Research Laboratory at the Division of Infectious Diseases, Department of Medicine at the University Hospital Freiburg.
The major focus of our work in recent years was the study of enterococcal pathogenesis
with particular emphasis on carbohydrate antigens. Our group has identified a
novel capsular polysaccharide in E. faecalis and E. faecium
that is the target of opsonic antibodies and therefore a possible vaccine candidate.
A second focus has been the molecular analysis of mechanisms of biofilm formation
in E. faecalis. Our laboratory has experience with a number of animal
models for enterococcal infections as well as with several in-vitro methods to
study virulence (such as invasion of and adhesion to eukaryotic cells, immunological
methods such as opsonophagocytic assays, and ELISAs to detected specific polysaccharides).
Dr. Jonas has extensive experience with several molecular typing methods. The
laboratory has successfully created several targeted deletion and insertion mutants
and has used transposon mutagenesis to create mutant libraries in several E.
faecalis strains. Dr. Huebner has worked until Sept. 2004 as Principal Investigator
at the Channing Laboratory (Brigham and Women’s Hospital) and Assistant
Professor at Harvard Medical School in Boston, USA.
Dr. J. Huebner, Bacterial Pathogenesis, Animal Models, Bacterial Genetics
Dr. D. Jonas, Molecular Typing Methods, Bacterial Genetics
G
Dr. D. Jonas, Molecular Typing Methods, Bacterial Genetics
Participant no 7
Robert Koch Institute
Wernigerode, Germany
Phone: +49 (0)30 - 18754-0
Fax: (+49) 3943679317
website
Robert Koch Institute
Wernigerode, Germany
Phone: +49 (0)30 - 18754-0
Fax: (+49) 3943679317
website
Description of the Institute
The Robert Koch Institute (RKI); Germany, is the central federal institution responsible for disease control and prevention and is therefore the central federal reference institution for both applied and response-orientated research as well as for the Public Health Sector. Apart from the enforcement of special laws, the tasks at the RKI include the legal obligation to compile scientific findings as a basis for political decisions concerning health issues. The RKI therefore communicates and cooperates with partners in the scientific sector, the Public Health Service and the Health Care Sector. The institute has major responsibilities in the field of scientific investigation, epidemiologic and medical analysis and evaluation of dangerous diseases and those with a high prevalence or of increased public or health-related political significance
The Unit “Nosocomial Infections” within the Department “Infectious Diseases” is a partner within this project. We are primarily concerned with surveying and studying the emergence and spread of those bacterial nosocomial pathogens that can act as indicators of hospital hygiene efficacy and rational antibacterial chemotherapy. Although our work currently focuses on MRSA and enterococci, further studies of gram-negatives with extended spectrum beta-lactamases and cephamycinases have been initiated. Of particular interest is the spread and evolution of newly emerging resistance characteristics, of multiresistant strains and of epidemic hospital strains. These studies are based mainly on molecular typing and population studies and on the identification of genetic determinants for antibiotic resistance and pathogenicity. In addition, we have projects aimed at developing advanced diagnostic methodologies (microarrays) and at identifying agricultural and environmental reservoirs of antibiotic resistance genes. The unit hosts the German National Reference Centre for Staphylococci.
The Robert Koch Institute (RKI); Germany, is the central federal institution responsible for disease control and prevention and is therefore the central federal reference institution for both applied and response-orientated research as well as for the Public Health Sector. Apart from the enforcement of special laws, the tasks at the RKI include the legal obligation to compile scientific findings as a basis for political decisions concerning health issues. The RKI therefore communicates and cooperates with partners in the scientific sector, the Public Health Service and the Health Care Sector. The institute has major responsibilities in the field of scientific investigation, epidemiologic and medical analysis and evaluation of dangerous diseases and those with a high prevalence or of increased public or health-related political significance
The Unit “Nosocomial Infections” within the Department “Infectious Diseases” is a partner within this project. We are primarily concerned with surveying and studying the emergence and spread of those bacterial nosocomial pathogens that can act as indicators of hospital hygiene efficacy and rational antibacterial chemotherapy. Although our work currently focuses on MRSA and enterococci, further studies of gram-negatives with extended spectrum beta-lactamases and cephamycinases have been initiated. Of particular interest is the spread and evolution of newly emerging resistance characteristics, of multiresistant strains and of epidemic hospital strains. These studies are based mainly on molecular typing and population studies and on the identification of genetic determinants for antibiotic resistance and pathogenicity. In addition, we have projects aimed at developing advanced diagnostic methodologies (microarrays) and at identifying agricultural and environmental reservoirs of antibiotic resistance genes. The unit hosts the German National Reference Centre for Staphylococci.
• strain collection of several hundred enterococcal strains pre-selected for special resistances and other features and from different sources (animal, sewage, human colonization/infection/outbreak related)
• strain collection of other related bacterial isolates used in several phases of the project (staphylococci, lactobacilli, lactococci, other anaerobic bacteria – used for horizontal gene transfer experiments)
• experiences in molecular bacterial strain typing for more than a decade*
• great experiences in many modern diagnostic and typing approaches applied within the project (PCR, PFGE, RT PCR, DNA array technology)*
• scientific experiences in typing of mobile elements (transposons, plasmids) allowing horizontal gene transfer in enterococci*
• profound scientific knowledge and expertise about population biology and species and subspecies identification*
* shown by publications in peer-reviewed journals
• strain collection of other related bacterial isolates used in several phases of the project (staphylococci, lactobacilli, lactococci, other anaerobic bacteria – used for horizontal gene transfer experiments)
• experiences in molecular bacterial strain typing for more than a decade*
• great experiences in many modern diagnostic and typing approaches applied within the project (PCR, PFGE, RT PCR, DNA array technology)*
• scientific experiences in typing of mobile elements (transposons, plasmids) allowing horizontal gene transfer in enterococci*
• profound scientific knowledge and expertise about population biology and species and subspecies identification*
* shown by publications in peer-reviewed journals
Prof. Dr. W. Witte, All fields mentioned under point 2
Dr. I. Klare, Strain typing, susceptibility testing, expertise working with anaerobic bacteria
Dr. G. Werner, Strain typing, molecular characterization of strains and their elements (genes, transposons, plasmids), establishing new diagnostic tools
Dr. U. Nuebel, Population biology / species and subspecies identification and typing, establishing new diagnostic tools, array technology
Dr. B. Strommenger, expertise in molecular diagnostics and array design, hybridisation and evaluation of data
H
Dr. I. Klare, Strain typing, susceptibility testing, expertise working with anaerobic bacteria
Dr. G. Werner, Strain typing, molecular characterization of strains and their elements (genes, transposons, plasmids), establishing new diagnostic tools
Dr. U. Nuebel, Population biology / species and subspecies identification and typing, establishing new diagnostic tools, array technology
Dr. B. Strommenger, expertise in molecular diagnostics and array design, hybridisation and evaluation of data
Participant no 8
Hospital Ramon y Cajal
Madrid, Spain
Phone: 91 336 80 00
Fax: (+34) 913368809
website
Hospital Ramon y Cajal
Madrid, Spain
Phone: 91 336 80 00
Fax: (+34) 913368809
website
Description of the Institute
The Hospital Universitario Ramón y Cajal (HRC) is a public 1,200-bed university teaching hospital (Alcalá de Henares University) providing pediatric and adult medical and surgical care to the North-East region of Madrid, Spain. The institution covers specialized health care to about 600.000 habitants population.
The Microbiology Department of the HRYC has been historically involved in the study of the mechanisms of resistance to antibiotics. Apart from its responsibilities in the diagnostic of infections, the Department is well-equipped with specialized laboratories in molecular genetics. Their main interests are: i) characterization of antibiotic resístance mechanisms; ii) molecular epidemiology of epidemicity markers (antibiotic resístance and putative virulence traits), iii) relationship among antibiotic consumption and antibiotic resistance; iv) population biology of microorganisms involved in hospital infections; v) mechanisms of bacterial variability (hyper-mutation) and selection of antibiotic resistance variants, and biological cost of resistance.
Currently, we are working on different models linking population biology and characterization of the genetics of antibiotic resistance in different Enterobacteriaceae producing extended-spectrum beta lactamases; in Enterococcus faecium and Enterococcus faecalis, in microorganisms associated to cystic fibrosis (Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp.) and in respiratory pathogens as Streptococcus pneumoniae and Haemophilus influenzae.
The Hospital Universitario Ramón y Cajal (HRC) is a public 1,200-bed university teaching hospital (Alcalá de Henares University) providing pediatric and adult medical and surgical care to the North-East region of Madrid, Spain. The institution covers specialized health care to about 600.000 habitants population.
The Microbiology Department of the HRYC has been historically involved in the study of the mechanisms of resistance to antibiotics. Apart from its responsibilities in the diagnostic of infections, the Department is well-equipped with specialized laboratories in molecular genetics. Their main interests are: i) characterization of antibiotic resístance mechanisms; ii) molecular epidemiology of epidemicity markers (antibiotic resístance and putative virulence traits), iii) relationship among antibiotic consumption and antibiotic resistance; iv) population biology of microorganisms involved in hospital infections; v) mechanisms of bacterial variability (hyper-mutation) and selection of antibiotic resistance variants, and biological cost of resistance.
Currently, we are working on different models linking population biology and characterization of the genetics of antibiotic resistance in different Enterobacteriaceae producing extended-spectrum beta lactamases; in Enterococcus faecium and Enterococcus faecalis, in microorganisms associated to cystic fibrosis (Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp.) and in respiratory pathogens as Streptococcus pneumoniae and Haemophilus influenzae.
Our group is excellently located to provide to the consortium access to suitable
well characterised collections of strains from different clinical origins (outpatients,
standard and intensive hospital care), from one of the European countries with
a low prevalence of vancomycin resistance, but where the clones that have spread
such resistance in other areas are already widely present in the hospital setting.
We have a long expertise in analyzing by genetic methods the population structure
of Enterococci, and in characterizing the mechanisms of resistance and the genetic
neighbourhood of resistance genes. We are also proficient in measuring comparative
fitness using competition experiments in mixed cultures exposed to various/variable
environments, as well as in evaluating biological costs of antibiotic resistance
both in vitro and in some animal models. We are also experienced in amensalistic
bacterial interactions, and we have a comprehensive collection of Enterococcus
from different origins producing well-characterized bacteriocins.
Dr. F Baquero, Bacterial interactions: Competition/Cost/Selection
Dr. T M Coque, Molecular genetics and molecular epidemiology
Dr. R Canton, Clinical diagnostic microbiology
Dr. M Francia, Molecular genetics and molecular epidemiology
P Ruíz-Garbajosa, Molecular epidemiology
Dr. R del Campo, Bacteriocins; normal flora
Dr. J Galán, Molecular genetics
C Novais, Molecular epidemiology
J Fortún, Infection Control policies
I
Dr. T M Coque, Molecular genetics and molecular epidemiology
Dr. R Canton, Clinical diagnostic microbiology
Dr. M Francia, Molecular genetics and molecular epidemiology
P Ruíz-Garbajosa, Molecular epidemiology
Dr. R del Campo, Bacteriocins; normal flora
Dr. J Galán, Molecular genetics
C Novais, Molecular epidemiology
J Fortún, Infection Control policies
Participant no 9
National Medicines Institute
Warszawa, Poland
Phone: 022-851-43-69
Fax: (+48) 22 841 29 49
website
National Medicines Institute
Warszawa, Poland
Phone: 022-851-43-69
Fax: (+48) 22 841 29 49
website
Description of the Institute
Division of Microbiology of NMI; formerly Sera and Vaccines Central Research Laboratory; Polish Centre of Excellence (consisting of three departments, Clinical Microbiology and Epidemiology, Molecular Microbiology, and Vaccines and Infections Prophylaxis; the head Prof. Waleria Hryniewicz MD, PhD). Division of Microbiology of NMI is focused on various aspects of clinical microbiology and molecular epidemiology of bacterial infections. One of its major fields of interest is the population structure of selected gram-positive pathogens, including vancomycin-resistant enterococci (VRE). For that purpose, established methods of typing are used as well as novel ones are introduced and standardized by the group. We are also involved in the basic research on virulence factors of enterococci and staphylococci. Members of this team have a big expertise in microbiology, epidemiology and molecular biology, and are involved in the long-going collaboration with numerous health centres all over Poland and abroad. For several years, they have been involved in numerous international scientific projects: STAPH, ALEXANDER, RESIST, SENTRY/ENARE, ESAR, EARSS, and US-Poland Maria Sklodowska-Curie Joint Fund (5FP).
Division of Microbiology of NMI; formerly Sera and Vaccines Central Research Laboratory; Polish Centre of Excellence (consisting of three departments, Clinical Microbiology and Epidemiology, Molecular Microbiology, and Vaccines and Infections Prophylaxis; the head Prof. Waleria Hryniewicz MD, PhD). Division of Microbiology of NMI is focused on various aspects of clinical microbiology and molecular epidemiology of bacterial infections. One of its major fields of interest is the population structure of selected gram-positive pathogens, including vancomycin-resistant enterococci (VRE). For that purpose, established methods of typing are used as well as novel ones are introduced and standardized by the group. We are also involved in the basic research on virulence factors of enterococci and staphylococci. Members of this team have a big expertise in microbiology, epidemiology and molecular biology, and are involved in the long-going collaboration with numerous health centres all over Poland and abroad. For several years, they have been involved in numerous international scientific projects: STAPH, ALEXANDER, RESIST, SENTRY/ENARE, ESAR, EARSS, and US-Poland Maria Sklodowska-Curie Joint Fund (5FP).
The group of Prof. Hryniewicz will coordinate research in the WP 2 (and all the
subjects relevant in the other WPs) by collecting, receiving, phenotyping and
genotyping E. faecium and E. faecalis isolates from different
sources by PFGE and MLST, and by collecting and analysing indispensable epidemiological
information. Concerning our participation in the WP3, we will obtain and provide
isolates harbouring the resistance genes on self-replicating plasmids, prophages,
transposons, integrons and other possible elements, capable of horizontal transfer
and we will be directly involved in their analysis by PCR/RFLP techniques and
sequencing. Furthermore, we will determine their transferability in vitro
(e.g., by conjugation to the antibiotic-susceptible host). Our work in the WP5
will be a direct continuation of our role as the coordinator of WP2, using our
expertise in isolation and purification of pathogenicity factors of protein nature
from Enterococcus spp. We plan as well to participate in the research
on polymorphism of virulence associated genes of Enterococcus spp. Techniques,
strains, expertise and materials for genotyping and pathogenicity studies will
be actively exchanged among all the participants.
Prof. Dr. W. Hryniewicz, Expertise in microbiology and epidemiology
Dr. E Sadowy, Expertise in molecular biology and MLST
T Ozorowski, Infection control and hospital epidemiology
A. Jakubczak, Expertise in microbiology and molecular biology
Z Pietras, Expertise in microbiology and molecular biology; expertise in computing.
M Turzyñska, Expertise in microbiology
J
Dr. E Sadowy, Expertise in molecular biology and MLST
T Ozorowski, Infection control and hospital epidemiology
A. Jakubczak, Expertise in microbiology and molecular biology
Z Pietras, Expertise in microbiology and molecular biology; expertise in computing.
M Turzyñska, Expertise in microbiology
Participant no 10
Winclove Bio Industries BV
Amsterdam, The Netherlands
Phone: +31 20 435 02 35
Fax: (+31) 204350236
website
Winclove Bio Industries BV
Amsterdam, The Netherlands
Phone: +31 20 435 02 35
Fax: (+31) 204350236
website
Description of the Institute
Winclove Bio Industries is a company that develops and produces probiotic food supplements. Winclove develops multispecies probiotics; this means that specific combinations of probiotic bacteria are selected for specific applications. This is often done in cooperation with several research partners; universities and academic hospitals.
Winclove is a small company (<20 employees); however a large part of the personnel is working in Research & Development. Besides the development of specific probiotic mixtures, Winclove invests in making stable products, which have a long shelf life at room temperature. Besides the product is tested for its capacity of surviving the gastro-intestinal tract. This makes Winclove an important research partner for many research parties. At the moment products of Winclove are being used in several large research projects in the Netherlands.
Winclove Bio Industries is a company that develops and produces probiotic food supplements. Winclove develops multispecies probiotics; this means that specific combinations of probiotic bacteria are selected for specific applications. This is often done in cooperation with several research partners; universities and academic hospitals.
Winclove is a small company (<20 employees); however a large part of the personnel is working in Research & Development. Besides the development of specific probiotic mixtures, Winclove invests in making stable products, which have a long shelf life at room temperature. Besides the product is tested for its capacity of surviving the gastro-intestinal tract. This makes Winclove an important research partner for many research parties. At the moment products of Winclove are being used in several large research projects in the Netherlands.
One of the project objectives is “to modulate human enteral colonization
with HiRECC by applying protective commensals”. It is hypothesized that
probiotics will decrease the incidence of gut colonization and intestinal load
with multi-resistant HiRECC among hospitalized patients. Since Winclove has a
large collection of >50 different probiotic strains, it is possible to define
selection criteria for probiotic bacteria that have the highest potential in this
application. Then a combination of the best potential strains can be developed.
Winclove has already a database with important information on these strains; e.g. antibiotic sensitivity data and the in vitro inhibition of pathogenic bacteria, including E. faecium. Recently research has been performed on probiotic strains and their capacity to inhibit the formation of biofilms of E. faecium and E. faecalis, with very promising results.
As mentioned before, Winclove can produce high quality probiotics that are stable at room temperature and also provide placebo for double-blind trials.
Winclove has already a database with important information on these strains; e.g. antibiotic sensitivity data and the in vitro inhibition of pathogenic bacteria, including E. faecium. Recently research has been performed on probiotic strains and their capacity to inhibit the formation of biofilms of E. faecium and E. faecalis, with very promising results.
As mentioned before, Winclove can produce high quality probiotics that are stable at room temperature and also provide placebo for double-blind trials.
Dr. H.M. Timmerman, Gut integritiy/ probiotics/ immunomodulation
M.I. Kuipers, Biofilm/probiotics
Ir. M. van Es,
K
M.I. Kuipers, Biofilm/probiotics
Ir. M. van Es,
Description of the Institute
One of IQ Corporation’s businesses is the generation and development of fully human monoclonal antibodies (humAbs) for post-exposure prophylactic or therapeutic application. In the past few years, IQ Corporation has developed a number of antibodies against different antigens from immunized and well characterized human donors.
IQ’s technology has high potential for the generation of antibody-based products for immune-modulation and for the replacement of currently used Ig preparations derived from blood of volunteers. Herman Groen and his research team have improved their technology for the development of humAb-producing-hybridomas to a level where it can be implemented routinely and with high efficiency for the development of humAbs against a large variety of targets from well-immunized or exposure-recovered blood donors. In the past 5 years, the team has developed humAbs against a number of disease indications which are now in different stages of development. IQ’s lead product is a fully in vitro and in vivo neutralizing humAb against Anthrax’s Lethal Toxin which is scheduled to enter Phase I in mid 2007. IQ is collaborating with several academic groups, with the CDC, the FDA and the US Naval Medical Research Center on a number of projects.
One of IQ Corporation’s businesses is the generation and development of fully human monoclonal antibodies (humAbs) for post-exposure prophylactic or therapeutic application. In the past few years, IQ Corporation has developed a number of antibodies against different antigens from immunized and well characterized human donors.
IQ’s technology has high potential for the generation of antibody-based products for immune-modulation and for the replacement of currently used Ig preparations derived from blood of volunteers. Herman Groen and his research team have improved their technology for the development of humAb-producing-hybridomas to a level where it can be implemented routinely and with high efficiency for the development of humAbs against a large variety of targets from well-immunized or exposure-recovered blood donors. In the past 5 years, the team has developed humAbs against a number of disease indications which are now in different stages of development. IQ’s lead product is a fully in vitro and in vivo neutralizing humAb against Anthrax’s Lethal Toxin which is scheduled to enter Phase I in mid 2007. IQ is collaborating with several academic groups, with the CDC, the FDA and the US Naval Medical Research Center on a number of projects.
Q will be developing fully human mAb-producing hybridomas from blood of immunized
or recovered individuals. These humAbs will be produced and purified by IQ in
quantities sufficient for the other partners to perform their in vitro
and in vivo efficacy studies.
Dr. H Groen, 18 yrs experience in immunology and the development of mAbs, 6 yrs experience in the development of human mAbs
H Westra, 21 yrs experience in lab work, 5.5 yrs experience in dev human mAbs
K Slopsema, 25 yrs experience in lab work, 5.5 yrs experience in dev human mAbs
W Steeman, 4 yrs experience in lab work, 1 yr in dev human mAbs
L
H Westra, 21 yrs experience in lab work, 5.5 yrs experience in dev human mAbs
K Slopsema, 25 yrs experience in lab work, 5.5 yrs experience in dev human mAbs
W Steeman, 4 yrs experience in lab work, 1 yr in dev human mAbs
Participant no 12
Biomade Technology BV
Groningen, The Netherlands
Phone: +31 50 363 5246
Fax: (+31) 50 363 4429
website
Biomade Technology BV
Groningen, The Netherlands
Phone: +31 50 363 5246
Fax: (+31) 50 363 4429
website
Description of the Institute
Biomade Technology is a multidisciplinary research organization founded in 2000 dedicated to developing nanobiotechnologies. We employ 35 highly qualified Ph.D. and technical staff with backgrounds in biochemistry, organic and physical chemistry, molecular biology, microbiology, pharmacology, genetics, and physics.
Biomade is a research institute whose mission is to develop and exploit nanobiotechnologies. Expertise area; delivery and controlled release systems for small and large therapeutic molecules, vaccines and genetic material.
Biomade developed an antigen delivery and adjuvant system, and has established collaborations with partners for pneumococcal and malaria vaccines.
Biomade Technology is a multidisciplinary research organization founded in 2000 dedicated to developing nanobiotechnologies. We employ 35 highly qualified Ph.D. and technical staff with backgrounds in biochemistry, organic and physical chemistry, molecular biology, microbiology, pharmacology, genetics, and physics.
Biomade is a research institute whose mission is to develop and exploit nanobiotechnologies. Expertise area; delivery and controlled release systems for small and large therapeutic molecules, vaccines and genetic material.
Biomade developed an antigen delivery and adjuvant system, and has established collaborations with partners for pneumococcal and malaria vaccines.
Mucosal immunization is attractive from the point of view that it can elicit responses that block adherence, colonization and/or entry of pathogens at mucosal surfaces. Despite the advantages of mucosal vaccine delivery, this route of administration poses vaccine developers for new challenges. Mucosal vaccine delivery requires powerful delivery-adjuvant technology, which also needs to be safe and affordable. Biomade Technology recently developed a novel non-living bacterial delivery system that: (i) has strong adjuvant properties; (ii) is safe in animal models, (iii) is simple to produce at low costs and thus also eligible for production in developing countries, (iv) allows needle-free administrations and (v) is very suitable for up-scaling. The technology is based on the food-grade Gram-positive bacterium Lactococcus lactis that is not genetically modified. These bacterial particles have a built-in adjuvant activity and are therefore referred to as Gram-positive Enhancer Matrix (GEM) particles. Antigens are attached to the bacterial particles by means of a proprietary Protein Anchor domain. Binding of Protein Anchor fusions is specific, occurs with high affinity and allows dense loading of the bacterial particles (up to 10exp5 – 10exp6 molecules per particle). The procedure eliminates the need of pre-purification of antigens.
Biomade’s antigen delivery technology has the following characteristics:
• High loading capacity of antigens
• No need for additional adjuvant
• Highly suitable for multivalent vaccines
• Stable in a dry form at room temperature
• Increased protection of protein antigens to proteolytic digestion
• Non-living, therefore controllable
• No recombinant DNA
• No endotoxins like LPS
• No risk of revertance to pathogenicity.
Biomade’s vaccine delivery technology was shown to elicit humoral and cellular, local and systemic immune responses towards, bacterial, viral and parasitic antigens. We have studied the efficacy of our vaccines towards the respiratory tract pathogen Streptococcus pneumoniae. This pathogen colonizes the nasal cavity and causes diseases like meningitis, sepsis and pneumoniae in humans. A murine nasal immunization and challenge model for pneumococcal pneumoniae has been set up in which it was shown that the local immune response reduced bacterial carriage in the nasal cavity. In addition, high levels of protective humoral systemic immunity were obtained in this model. In oral immunization experiments in rabbits we have shown that our vaccine delivery technology stimulates both the production of local sIgA in the gastrointestinal tract and systemic antibodies specific for a Plasmodium falciparum malaria antigen. Furthermore, we have studied the efficacy of our malaria vaccines towards development of disease by the malaria parasite. For this purpose, we used a model that exploites mosquitoes infected with the Plasmodium berghei malaria parasite to challenge immunized mice. Also in this model we achieved high levels of protection, which was based on both humoral and cellular responses.
Biomade’s expertise in the development of mucosal vaccines and mucosal challenge models can be directly applied in the present project. Target antigens identified in the project will be cloned, expressed and formulated with Biomade’s vaccine delivery technology. Mucosal immunizations will be carried out in suitable animal models.
• High loading capacity of antigens
• No need for additional adjuvant
• Highly suitable for multivalent vaccines
• Stable in a dry form at room temperature
• Increased protection of protein antigens to proteolytic digestion
• Non-living, therefore controllable
• No recombinant DNA
• No endotoxins like LPS
• No risk of revertance to pathogenicity.
Biomade’s vaccine delivery technology was shown to elicit humoral and cellular, local and systemic immune responses towards, bacterial, viral and parasitic antigens. We have studied the efficacy of our vaccines towards the respiratory tract pathogen Streptococcus pneumoniae. This pathogen colonizes the nasal cavity and causes diseases like meningitis, sepsis and pneumoniae in humans. A murine nasal immunization and challenge model for pneumococcal pneumoniae has been set up in which it was shown that the local immune response reduced bacterial carriage in the nasal cavity. In addition, high levels of protective humoral systemic immunity were obtained in this model. In oral immunization experiments in rabbits we have shown that our vaccine delivery technology stimulates both the production of local sIgA in the gastrointestinal tract and systemic antibodies specific for a Plasmodium falciparum malaria antigen. Furthermore, we have studied the efficacy of our malaria vaccines towards development of disease by the malaria parasite. For this purpose, we used a model that exploites mosquitoes infected with the Plasmodium berghei malaria parasite to challenge immunized mice. Also in this model we achieved high levels of protection, which was based on both humoral and cellular responses.
Biomade’s expertise in the development of mucosal vaccines and mucosal challenge models can be directly applied in the present project. Target antigens identified in the project will be cloned, expressed and formulated with Biomade’s vaccine delivery technology. Mucosal immunizations will be carried out in suitable animal models.
Dr. T Bosma, Projectleader
Dr. S Audouy, Researcher, animal experiments
Ing. R Kanninga, Research Technician, Molecular Biology
Ing. V de Vries, Research Technician, animal experiments
Dr. S Audouy, Researcher, animal experiments
Ing. R Kanninga, Research Technician, Molecular Biology
Ing. V de Vries, Research Technician, animal experiments