Karen A Krogfelt | SSI (original) (raw)

Papers by Karen A Krogfelt

Research paper thumbnail of Prospective Studies on Asthma in

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Summary Background We hypothesize that perinatal exposures, in particular the human micro-biome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. Objective The aim of this study is to explore these interactions by conducting a longitudinal

Research paper thumbnail of Deep phenotyping of the unselected COPSAC 2010 birth cohort study

Clinical & Experimental Allergy, 2013

 Users may download and print one copy of any publication from the public portal for the purpose... more  Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Research paper thumbnail of Neonates colonized with pathogenic bacteria in the airways have a low‐grade systemic inflammation

Allergy, 2018

Background and objectivesThe development of childhood asthma is associated with neonatal coloniza... more Background and objectivesThe development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low‐grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low‐grade inflammation.MethodsBacterial colonization of the hypopharynx with Moraxella catharralis, Haemophilus influenzae, and/or Streptococcus pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort at age 1 month by culturing technique (N = 238) and by quantitative polymerase chain reaction (qPCR) technique (N = 249) and in the COPSAC2010 cohort by culturing at age 1 month (N = 622) and again at age 3 months (N = 613). Systemic low‐grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high‐sensitivity C‐...

Research paper thumbnail of Adhesin-dependent isolation and characterization of bacteria from their natural environment

Publisher Summary Understanding the physiology of bacteria grown in vivo in various hosts has bee... more Publisher Summary Understanding the physiology of bacteria grown in vivo in various hosts has been a difficult task. By using the adhesive properties of the microorganism, it is possible to isolate certain bacteria from their natural environment for further investigations. Pure cultures so obtained do not require growth on an artificial laboratory medium. The chapter describes the method for adhesin-dependent isolation and characterization of bacteria from their natural environment. It is performed by using a streptomycin-treated mouse as a host for a human Escherichia coli strain, producing type 1 fimbriae in vivo . Type 1 fimbriae bind specifically to D-mannose moieties. In this context, experiments were performed in which sepharose beads coupled with D-mannose were used for isolating bacterial cells from a fecal suspension, and/or from cecal mucus and cecal contents. Then, the isolated intact bacterial cells can be characterized by techniques such as electron microscopy, flow cytometry, and in situ hybridization. By electron microscopy, cell shape and surface components can be observed. A flow cytometer can be used for determining rapidly and with high precision the cell size of individual bacterial cells and the cell-size distribution in the isolated population. DNA content can be measured and the number of genomes per cell calculated. By in situ hybridization with labeled ribosomal RNA probes, the rRNA can be measured, which will reflect the metabolic activity of the bacterial cell in the host.

Research paper thumbnail of Screening Escherichia coli, Enterococcus faecalis, and Clostridium perfringens as Indicator Organisms in Evaluating Pathogen-Reducing Capacity in Biogas Plants

Microbial Ecology, 2009

This study was conducted to identify an indicator organism(s) in evaluating the pathogen-reducing... more This study was conducted to identify an indicator organism(s) in evaluating the pathogen-reducing capacity of biogas plants. Fresh cow manure containing 10 4 to 10 5 colony forming unit (CFU) per milliliter of Escherichia coli and Enterococcus faecalis along with an inoculated Clostridium perfringens strain were exposed to 37°C for 15 days, 55°C for 48 h, and 70°C for 24 h. C. perfringens was the most heat-resistant organism followed by E. faecalis, while E. coli was the most heat-sensitive organism. E. coli was reduced below detection limit at all temperatures with log 10 reductions of 4.94 (10 s), 4.37 (40 min), and 2.6 (5 days) at 70°C, 55°C, and 37°C, respectively. Maximum log 10 reductions for E. faecalis were 1.77 at 70°C (1 day), 1.7 at 55°C (2 days) and 3.13 at 37°C (15 days). For C. perfringens, maximum log 10 reduction at 37°C was 1.35 log 10 units (15 days) compared to less than 1 unit at 55 and 70°C. Modeling results showed that E. faecalis and C. perfringens had higher amount of heat-resistant fraction than E. coli. Thus, E. faecalis and C. perfringens can be used as indicator organisms to evaluate pathogen-reducing capacity in biogas plants at high temperatures of 55°C and 70°C while at 37°C E. coli could also be included as indicator organism.

Research paper thumbnail of Antibiotic use during pregnancy alters the commensal vaginal microbiota

Clinical Microbiology and Infection, 2014

Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant wom... more Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant women. Therefore, we studied the effect of antibiotic administration during pregnancy on commensal vaginal bacterial colonization at gestational week 36. Six hundred and sixty-eight pregnant women from the novel unselected Copenhagen Prospective Studies on Asthma in Childhood (COPSAC 2010) pregnancy cohort participated in this analysis. Detailed information on oral antibiotic prescriptions during pregnancy filled at the pharmacy was obtained and verified prospectively. Vaginal samples were obtained at pregnancy week 36 and cultured for bacteria. Women who received oral antibiotics during any pregnancy trimester had an increased rate of colonization by Staphylococcus species in the vaginal samples as compared with samples obtained from women without any antibiotic treatment during pregnancy (adjusted OR 1.63, 95% CI 1.06-2.52, p 0.028). Oral antibiotic administration in the third trimester were also associated with increased colonization by Staphylococcus species (adjusted OR 1.98, 95% CI 1.04-3.76, p 0.037). These bacteriological changes were associated with urinary tract infection antibiotics. Women treated in the third trimester of pregnancy were more often colonized by Escherichia coli than women without antibiotic treatment in the third trimester (adjusted OR 1.91, 95% CI 1.04-3.52, p 0.038). This change was associated with respiratory tract infection (RTI) antibiotics. We did not observe any significant changes in vaginal Streptococcus agalactiae (group B streptoccocus) or Staphylococcus aureus colonization following antibiotic treatment in pregnancy. Antibiotic administration during pregnancy leads to alterations in the vaginal microbiological ecology prior to birth, with potential morbidity, and long-term effects on the early microbial colonization of the neonate.

Research paper thumbnail of Cluster of Legionnaires’ disease in a newly built block of flats, Denmark, December 2008 – January 2009

Eurosurveillance, 2011

, two persons contracted Legionnaires' disease in a newly built block of flats in a suburb of Cop... more , two persons contracted Legionnaires' disease in a newly built block of flats in a suburb of Copenhagen in Denmark. Polymerase chain reaction and culture was used to diagnose Legionnaires' disease in this cluster. Isolates from both patients tested positive for Legionella pneumophila serogroup 1 subgroup Philadelphia sequence type 1 and the same strain was detected in hot water samples taken from the residential area indicating that the hot water supply system was the most likely source of infection. Legionella was not detected in the cold water. Two interventions were conducted to limit the Legionella colonisation of the piping and storage tanks and the effect was monitored by investigating water samples from various sites in the block of flats. Only the second intervention had a sufficient effect on the Legionella colonisation. The cluster described here points to several risk factors regarding growth of Legionella in hot water systems: (i) stagnancy of water from when the building is constructed and piping installed and until residents move in, (ii) stagnancy and low temperature (from room temperature to approximately 38 0 C) of water in shower hoses and (iii) failure in operation of and control measures for the hot water system.

Research paper thumbnail of From Mecillinam-Treated

persistence of Escherichia coli in urinary bladders

Research paper thumbnail of Increased abundance of proteobacteria in aggressive Crohn’s disease seven years after diagnosis

Scientific Reports, 2019

Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We ... more Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn’s disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed ...

Research paper thumbnail of A10 an Ulcerative Colitis Escherichia Coli Pathobiont Colonizes the Intestinal Mucosa of Susceptible Hosts and Promotes Colitis via Hemolysin Production

Journal of the Canadian Association of Gastroenterology, 2018

Research paper thumbnail of Antibody development to Fusobacterium necrophorum in patients with peritonsillar abscess

A polymicrobial mixture of aerobic and anaerobic bacteria is commonly recovered from peritonsilla... more A polymicrobial mixture of aerobic and anaerobic bacteria is commonly recovered from peritonsillar abscess (PTA) aspirates. Previous studies have suggested a role for Fusobacterium necrophorum (FN) in the development of PTA. The purpose of the current study was to explore whether anti-FN antibodies were produced in patients with PTA. We developed a novel immunofluorescence-based method to measure anti-FN antibody levels in acute and convalescent sera from 15 patients with PTA and 47 patients with chronic tonsillar conditions (controls) undergoing acute or elective tonsillectomy, respectively. Bacterial cultures were performed on tonsillar cores and surfaces, pus aspirates, and blood. An increase in anti-FN antibody levels (of at least doubling of the previous level) was observed in 8 of 11 (73 %) PTA patients with FN-positive pus aspirate cultures (FN-positive patients). In contrast, the four FN-negative PTA patients did not have an increase in anti-FN antibody levels (p=0.026). The change in anti-FN antibody levels in FN-positive PTA patients was also significantly greater than that for FN-positive electively tonsillectomized patients (p = 0.0014) and all electively tonsillectomized patients (p<0.001). Our results validate FN as a significant and prevalent pathogen in PTA. This finding has implications for the diagnostic work-up of PTA and may also have implications for the treatment of acute tonsillitis.

Research paper thumbnail of Utilization of the mouse large intestine to select an Escherichia coli F-18 DNA sequence that enhances colonizing ability and stimulates synthesis of type 1 fimbriae

Infection and Immunity, 1993

Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomyci... more Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomycin-treated mouse large intestine. E. coli F-18 Col-, a derivative of E. coli F-18 which no longer makes the E. coli F-18 colicin, colonizes the large intestine as well as E. coli F-18 when fed to mice alone but is eliminated when fed together with E. coli F-18. Random sequences of E. coli F-18 DNA were cloned into pRLB2, a par-B-stabilized derivative of pHC79. The entire gene library was transformed into E. coli F-18 Col- and fed to streptomycin-treated mice. The mouse large intestine selected a predominant clone which contained a recombinant plasmid (pRLB7) that enhanced E. coli F-18 Col- colonizing ability 100-fold but did not stimulate colicin synthesis. Moreover, pRLB7 simultaneously improved the survival of E. coli F-18 Col- in stationary phase in vitro, utilizing nutrients derived from mouse cecal mucus, and stimulated synthesis of both type 1 fimbriae and three E. coli F-18 Col- ou...

Research paper thumbnail of Isolation and characterization of an attenuated strain of Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader

Applied and environmental microbiology, 1997

Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a repo... more Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a reported 50% lethal dose (LD50) of 1.05 x 10(7) CFU when given intranasally to C3H/HeJ mice (S.E. George, M.J. Kohan, M.I. Gilmour, M.S. Taylor, H.G. Brooks, J.P. Creason, and L.D. Claxton, Appl. Environ, Microbiol. 59:3585-3591, 1993). AC869 was serotyped as O6 when grown in CD-1 mouse cecal and lung mucus but could not be assigned an O serotype when grown in Luria broth (LB). After growth in mouse cecal mucus, a less virulent mutant, AC869-11, was isolated from AC869 by using bacteriophage E79, which adsorbs to the O side chain of lipopolysaccharide (LPS). AC869-11 produced significantly less O antigen on its LPS than AC869 when grown in mouse lung and cecal mucus. The mutant also produced half the amount of exoenzyme S and 16-fold less extracellular protease than AC869 and was more sensitive than its parent to a number of antibiotics when grown either in LB or in mouse lung mucus. AC869-1...

Research paper thumbnail of Associations between common intestinal parasites and bacteria in humans as revealed by qPCR

European Journal of Clinical Microbiology & Infectious Diseases, 2016

Research paper thumbnail of Physiological state of Escherichia coli BJ4 growing in the large intestines of streptomycin-treated mice

Journal of Bacteriology, 1995

Growth rates of Escherichia coli BJ4 colonizing the large intestine of streptomycin-treated mice ... more Growth rates of Escherichia coli BJ4 colonizing the large intestine of streptomycin-treated mice were estimated by quantitative hybridization with rRNA target probes and by epifluorescence microscopy. The ribosomal contents in bacteria isolated from the cecal mucus, cecal contents, and feces were measured and correlated with the ribosomal contents of bacteria growing in vitro at defined rates. The data suggest that E. coli BJ4 grows at an overall high rate in the intestine. However, when taking into account the total intestinal volume and numbers of bacteria present in cecal mucus, cecal contents, and feces, we suggest that E. coli BJ4 in the intestine consists of two populations, one in the mucus which has an apparent generation time of 40 to 80 min and one in the luminal contents which is static.

Research paper thumbnail of Epidemiological and serological investigation of a waterborneCampylobacter jejunioutbreak in a Danish town

Epidemiology and Infection, 2016

SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobac... more SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobactergastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis.Campylobacter jejunibelonging to two relatedflaAtypes were isolated from stool samples. Serum antibody levels againstCampylobacterwere significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-wate...

Research paper thumbnail of Lipopolysaccharide’s Role in the Association of Salmonella Cells to the Mouse Intestine Studied By Ribosomal in Situ Hybridization

Advances in Experimental Medicine and Biology, 1996

The majority of microbes most probably exist in nature in close association with particular surfa... more The majority of microbes most probably exist in nature in close association with particular surfaces. The adhesive properties of microorganisms were first recognized at the beginning of this century. Since then it has been shown that bacterial adhesion is important in plant and animal hosts, pathogenesis, medical devices, aquatic and soil ecosystems, biodegradation, and industrial processes.

Research paper thumbnail of Colonization of bacteria in the mouse intestine-Visualized by in situ hybridization of rRNA

Research paper thumbnail of Estimation of incidences of infectious diseases based on antibody measurements

Statistics in Medicine, 2009

Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a gi... more Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a given disease based on cases notified to routine public health surveillance. This is especially true for diseases that are often present in mild forms as for example diarrhoea caused by foodborne bacterial infections. This study presents a Bayesian approach for obtaining incidence estimates by use of measurements of serum antibodies against Salmonella from a cross-sectional study. By comparing these measurements with antibody measurements from a follow-up study of infected individuals it was possible to estimate the time since last infection for each individual in the cross-sectional study. These time estimates were then converted into incidence estimates. Information about the incidence of Salmonella infections in Denmark was obtained by using blood samples from 1780 persons. The estimated incidence was about 0.094 infections per person year. This number corresponds to 325 infections per culture-confirmed case captured in the Danish national surveillance system. We present a novel approach, termed as seroincidence, that has potentials to compare the sensitivity of public health surveillance between different populations, countries and over time.

Research paper thumbnail of K88 fimbrial antigens: identification of antigenic determinants by the use of synthetic peptides

Microbial Pathogenesis, 1987

Research paper thumbnail of Prospective Studies on Asthma in

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Summary Background We hypothesize that perinatal exposures, in particular the human micro-biome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. Objective The aim of this study is to explore these interactions by conducting a longitudinal

Research paper thumbnail of Deep phenotyping of the unselected COPSAC 2010 birth cohort study

Clinical & Experimental Allergy, 2013

 Users may download and print one copy of any publication from the public portal for the purpose... more  Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Research paper thumbnail of Neonates colonized with pathogenic bacteria in the airways have a low‐grade systemic inflammation

Allergy, 2018

Background and objectivesThe development of childhood asthma is associated with neonatal coloniza... more Background and objectivesThe development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low‐grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low‐grade inflammation.MethodsBacterial colonization of the hypopharynx with Moraxella catharralis, Haemophilus influenzae, and/or Streptococcus pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort at age 1 month by culturing technique (N = 238) and by quantitative polymerase chain reaction (qPCR) technique (N = 249) and in the COPSAC2010 cohort by culturing at age 1 month (N = 622) and again at age 3 months (N = 613). Systemic low‐grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high‐sensitivity C‐...

Research paper thumbnail of Adhesin-dependent isolation and characterization of bacteria from their natural environment

Publisher Summary Understanding the physiology of bacteria grown in vivo in various hosts has bee... more Publisher Summary Understanding the physiology of bacteria grown in vivo in various hosts has been a difficult task. By using the adhesive properties of the microorganism, it is possible to isolate certain bacteria from their natural environment for further investigations. Pure cultures so obtained do not require growth on an artificial laboratory medium. The chapter describes the method for adhesin-dependent isolation and characterization of bacteria from their natural environment. It is performed by using a streptomycin-treated mouse as a host for a human Escherichia coli strain, producing type 1 fimbriae in vivo . Type 1 fimbriae bind specifically to D-mannose moieties. In this context, experiments were performed in which sepharose beads coupled with D-mannose were used for isolating bacterial cells from a fecal suspension, and/or from cecal mucus and cecal contents. Then, the isolated intact bacterial cells can be characterized by techniques such as electron microscopy, flow cytometry, and in situ hybridization. By electron microscopy, cell shape and surface components can be observed. A flow cytometer can be used for determining rapidly and with high precision the cell size of individual bacterial cells and the cell-size distribution in the isolated population. DNA content can be measured and the number of genomes per cell calculated. By in situ hybridization with labeled ribosomal RNA probes, the rRNA can be measured, which will reflect the metabolic activity of the bacterial cell in the host.

Research paper thumbnail of Screening Escherichia coli, Enterococcus faecalis, and Clostridium perfringens as Indicator Organisms in Evaluating Pathogen-Reducing Capacity in Biogas Plants

Microbial Ecology, 2009

This study was conducted to identify an indicator organism(s) in evaluating the pathogen-reducing... more This study was conducted to identify an indicator organism(s) in evaluating the pathogen-reducing capacity of biogas plants. Fresh cow manure containing 10 4 to 10 5 colony forming unit (CFU) per milliliter of Escherichia coli and Enterococcus faecalis along with an inoculated Clostridium perfringens strain were exposed to 37°C for 15 days, 55°C for 48 h, and 70°C for 24 h. C. perfringens was the most heat-resistant organism followed by E. faecalis, while E. coli was the most heat-sensitive organism. E. coli was reduced below detection limit at all temperatures with log 10 reductions of 4.94 (10 s), 4.37 (40 min), and 2.6 (5 days) at 70°C, 55°C, and 37°C, respectively. Maximum log 10 reductions for E. faecalis were 1.77 at 70°C (1 day), 1.7 at 55°C (2 days) and 3.13 at 37°C (15 days). For C. perfringens, maximum log 10 reduction at 37°C was 1.35 log 10 units (15 days) compared to less than 1 unit at 55 and 70°C. Modeling results showed that E. faecalis and C. perfringens had higher amount of heat-resistant fraction than E. coli. Thus, E. faecalis and C. perfringens can be used as indicator organisms to evaluate pathogen-reducing capacity in biogas plants at high temperatures of 55°C and 70°C while at 37°C E. coli could also be included as indicator organism.

Research paper thumbnail of Antibiotic use during pregnancy alters the commensal vaginal microbiota

Clinical Microbiology and Infection, 2014

Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant wom... more Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant women. Therefore, we studied the effect of antibiotic administration during pregnancy on commensal vaginal bacterial colonization at gestational week 36. Six hundred and sixty-eight pregnant women from the novel unselected Copenhagen Prospective Studies on Asthma in Childhood (COPSAC 2010) pregnancy cohort participated in this analysis. Detailed information on oral antibiotic prescriptions during pregnancy filled at the pharmacy was obtained and verified prospectively. Vaginal samples were obtained at pregnancy week 36 and cultured for bacteria. Women who received oral antibiotics during any pregnancy trimester had an increased rate of colonization by Staphylococcus species in the vaginal samples as compared with samples obtained from women without any antibiotic treatment during pregnancy (adjusted OR 1.63, 95% CI 1.06-2.52, p 0.028). Oral antibiotic administration in the third trimester were also associated with increased colonization by Staphylococcus species (adjusted OR 1.98, 95% CI 1.04-3.76, p 0.037). These bacteriological changes were associated with urinary tract infection antibiotics. Women treated in the third trimester of pregnancy were more often colonized by Escherichia coli than women without antibiotic treatment in the third trimester (adjusted OR 1.91, 95% CI 1.04-3.52, p 0.038). This change was associated with respiratory tract infection (RTI) antibiotics. We did not observe any significant changes in vaginal Streptococcus agalactiae (group B streptoccocus) or Staphylococcus aureus colonization following antibiotic treatment in pregnancy. Antibiotic administration during pregnancy leads to alterations in the vaginal microbiological ecology prior to birth, with potential morbidity, and long-term effects on the early microbial colonization of the neonate.

Research paper thumbnail of Cluster of Legionnaires’ disease in a newly built block of flats, Denmark, December 2008 – January 2009

Eurosurveillance, 2011

, two persons contracted Legionnaires' disease in a newly built block of flats in a suburb of Cop... more , two persons contracted Legionnaires' disease in a newly built block of flats in a suburb of Copenhagen in Denmark. Polymerase chain reaction and culture was used to diagnose Legionnaires' disease in this cluster. Isolates from both patients tested positive for Legionella pneumophila serogroup 1 subgroup Philadelphia sequence type 1 and the same strain was detected in hot water samples taken from the residential area indicating that the hot water supply system was the most likely source of infection. Legionella was not detected in the cold water. Two interventions were conducted to limit the Legionella colonisation of the piping and storage tanks and the effect was monitored by investigating water samples from various sites in the block of flats. Only the second intervention had a sufficient effect on the Legionella colonisation. The cluster described here points to several risk factors regarding growth of Legionella in hot water systems: (i) stagnancy of water from when the building is constructed and piping installed and until residents move in, (ii) stagnancy and low temperature (from room temperature to approximately 38 0 C) of water in shower hoses and (iii) failure in operation of and control measures for the hot water system.

Research paper thumbnail of From Mecillinam-Treated

persistence of Escherichia coli in urinary bladders

Research paper thumbnail of Increased abundance of proteobacteria in aggressive Crohn’s disease seven years after diagnosis

Scientific Reports, 2019

Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We ... more Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn’s disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed ...

Research paper thumbnail of A10 an Ulcerative Colitis Escherichia Coli Pathobiont Colonizes the Intestinal Mucosa of Susceptible Hosts and Promotes Colitis via Hemolysin Production

Journal of the Canadian Association of Gastroenterology, 2018

Research paper thumbnail of Antibody development to Fusobacterium necrophorum in patients with peritonsillar abscess

A polymicrobial mixture of aerobic and anaerobic bacteria is commonly recovered from peritonsilla... more A polymicrobial mixture of aerobic and anaerobic bacteria is commonly recovered from peritonsillar abscess (PTA) aspirates. Previous studies have suggested a role for Fusobacterium necrophorum (FN) in the development of PTA. The purpose of the current study was to explore whether anti-FN antibodies were produced in patients with PTA. We developed a novel immunofluorescence-based method to measure anti-FN antibody levels in acute and convalescent sera from 15 patients with PTA and 47 patients with chronic tonsillar conditions (controls) undergoing acute or elective tonsillectomy, respectively. Bacterial cultures were performed on tonsillar cores and surfaces, pus aspirates, and blood. An increase in anti-FN antibody levels (of at least doubling of the previous level) was observed in 8 of 11 (73 %) PTA patients with FN-positive pus aspirate cultures (FN-positive patients). In contrast, the four FN-negative PTA patients did not have an increase in anti-FN antibody levels (p=0.026). The change in anti-FN antibody levels in FN-positive PTA patients was also significantly greater than that for FN-positive electively tonsillectomized patients (p = 0.0014) and all electively tonsillectomized patients (p<0.001). Our results validate FN as a significant and prevalent pathogen in PTA. This finding has implications for the diagnostic work-up of PTA and may also have implications for the treatment of acute tonsillitis.

Research paper thumbnail of Utilization of the mouse large intestine to select an Escherichia coli F-18 DNA sequence that enhances colonizing ability and stimulates synthesis of type 1 fimbriae

Infection and Immunity, 1993

Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomyci... more Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomycin-treated mouse large intestine. E. coli F-18 Col-, a derivative of E. coli F-18 which no longer makes the E. coli F-18 colicin, colonizes the large intestine as well as E. coli F-18 when fed to mice alone but is eliminated when fed together with E. coli F-18. Random sequences of E. coli F-18 DNA were cloned into pRLB2, a par-B-stabilized derivative of pHC79. The entire gene library was transformed into E. coli F-18 Col- and fed to streptomycin-treated mice. The mouse large intestine selected a predominant clone which contained a recombinant plasmid (pRLB7) that enhanced E. coli F-18 Col- colonizing ability 100-fold but did not stimulate colicin synthesis. Moreover, pRLB7 simultaneously improved the survival of E. coli F-18 Col- in stationary phase in vitro, utilizing nutrients derived from mouse cecal mucus, and stimulated synthesis of both type 1 fimbriae and three E. coli F-18 Col- ou...

Research paper thumbnail of Isolation and characterization of an attenuated strain of Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader

Applied and environmental microbiology, 1997

Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a repo... more Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a reported 50% lethal dose (LD50) of 1.05 x 10(7) CFU when given intranasally to C3H/HeJ mice (S.E. George, M.J. Kohan, M.I. Gilmour, M.S. Taylor, H.G. Brooks, J.P. Creason, and L.D. Claxton, Appl. Environ, Microbiol. 59:3585-3591, 1993). AC869 was serotyped as O6 when grown in CD-1 mouse cecal and lung mucus but could not be assigned an O serotype when grown in Luria broth (LB). After growth in mouse cecal mucus, a less virulent mutant, AC869-11, was isolated from AC869 by using bacteriophage E79, which adsorbs to the O side chain of lipopolysaccharide (LPS). AC869-11 produced significantly less O antigen on its LPS than AC869 when grown in mouse lung and cecal mucus. The mutant also produced half the amount of exoenzyme S and 16-fold less extracellular protease than AC869 and was more sensitive than its parent to a number of antibiotics when grown either in LB or in mouse lung mucus. AC869-1...

Research paper thumbnail of Associations between common intestinal parasites and bacteria in humans as revealed by qPCR

European Journal of Clinical Microbiology & Infectious Diseases, 2016

Research paper thumbnail of Physiological state of Escherichia coli BJ4 growing in the large intestines of streptomycin-treated mice

Journal of Bacteriology, 1995

Growth rates of Escherichia coli BJ4 colonizing the large intestine of streptomycin-treated mice ... more Growth rates of Escherichia coli BJ4 colonizing the large intestine of streptomycin-treated mice were estimated by quantitative hybridization with rRNA target probes and by epifluorescence microscopy. The ribosomal contents in bacteria isolated from the cecal mucus, cecal contents, and feces were measured and correlated with the ribosomal contents of bacteria growing in vitro at defined rates. The data suggest that E. coli BJ4 grows at an overall high rate in the intestine. However, when taking into account the total intestinal volume and numbers of bacteria present in cecal mucus, cecal contents, and feces, we suggest that E. coli BJ4 in the intestine consists of two populations, one in the mucus which has an apparent generation time of 40 to 80 min and one in the luminal contents which is static.

Research paper thumbnail of Epidemiological and serological investigation of a waterborneCampylobacter jejunioutbreak in a Danish town

Epidemiology and Infection, 2016

SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobac... more SUMMARYFollowing an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobactergastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis.Campylobacter jejunibelonging to two relatedflaAtypes were isolated from stool samples. Serum antibody levels againstCampylobacterwere significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-wate...

Research paper thumbnail of Lipopolysaccharide’s Role in the Association of Salmonella Cells to the Mouse Intestine Studied By Ribosomal in Situ Hybridization

Advances in Experimental Medicine and Biology, 1996

The majority of microbes most probably exist in nature in close association with particular surfa... more The majority of microbes most probably exist in nature in close association with particular surfaces. The adhesive properties of microorganisms were first recognized at the beginning of this century. Since then it has been shown that bacterial adhesion is important in plant and animal hosts, pathogenesis, medical devices, aquatic and soil ecosystems, biodegradation, and industrial processes.

Research paper thumbnail of Colonization of bacteria in the mouse intestine-Visualized by in situ hybridization of rRNA

Research paper thumbnail of Estimation of incidences of infectious diseases based on antibody measurements

Statistics in Medicine, 2009

Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a gi... more Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a given disease based on cases notified to routine public health surveillance. This is especially true for diseases that are often present in mild forms as for example diarrhoea caused by foodborne bacterial infections. This study presents a Bayesian approach for obtaining incidence estimates by use of measurements of serum antibodies against Salmonella from a cross-sectional study. By comparing these measurements with antibody measurements from a follow-up study of infected individuals it was possible to estimate the time since last infection for each individual in the cross-sectional study. These time estimates were then converted into incidence estimates. Information about the incidence of Salmonella infections in Denmark was obtained by using blood samples from 1780 persons. The estimated incidence was about 0.094 infections per person year. This number corresponds to 325 infections per culture-confirmed case captured in the Danish national surveillance system. We present a novel approach, termed as seroincidence, that has potentials to compare the sensitivity of public health surveillance between different populations, countries and over time.

Research paper thumbnail of K88 fimbrial antigens: identification of antigenic determinants by the use of synthetic peptides

Microbial Pathogenesis, 1987