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Engstrand, Lars
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Publications (10 of 53) Show all publications
Nilsson, A., Skarp, A., Johansson, C., Kaden, R., Engstrand, L. & Rautelin, H. (2018). Characterization of Swedish Campylobacter coli clade 2 and clade 3 water isolates. MicrobiologyOpen, 7(4), Article ID e00583.
Open this publication in new window or tab >>Characterization of Swedish Campylobacter coli clade 2 and clade 3 water isolates
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2018 (English)In: MicrobiologyOpen, ISSN 2045-8827, E-ISSN 2045-8827, Vol. 7, no 4, article id e00583Article in journal (Refereed) Published
Abstract [en]

Campylobacter jejuni and Campylobacter coli are important bacterial enteropathogens. Poultry is the best-known reservoir for Campylobacter infection but natural bodies of water have also been shown to be important pathways for transmission. Campylobacter can survive in cold water but most of the studies have focused on C. jejuni only. In this paper, we take a closer look at the biology and water survival strategies of C. coil. Eight C. coil isolates cultivated from raw (incoming) surface water at water plants in Sweden were characterized using whole-genome sequencing and phenotypical assays. Phylogenetic analysis assigned the Swedish water isolates to clades 2 and 3, known to include C. coil of environmental origin. In addition, 53 earlier published sequences of C. coil clade 2 and 3 from environmental waters were included for in silico analyses. Generally, clade 2 isolates had larger genomes, which included a functional tricarballylate utilization locus, while clade 3 isolates contained different genes involved in oxidative stress as well as putative virulence factors. The Swedish water isolates of clade 2 formed large, blurry bacterial colonies on agar, whereas clade 3 colonies were smaller. All Swedish isolates were motile, but clade 3 isolates formed larger motility zones on soft agar, and none of these isolates produced biofilm. Although water survival varied between the analyzed isolates, there were hardly any clade-specific significant differences. Our results highlight the diversity of C. coil in general, and show differences in metabolic capabilities and ways to handle oxidative stress between clade 2 and 3 water isolates.

Keywords
Campylobacter coli, phenotypic identification, waterborne pathogens, whole-genome sequencing
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-332076 (URN)10.1002/mbo3.583 (DOI)000440928500006 ()29424055 (PubMedID)
Funder
Swedish Research Council Formas, 221- 2012-1442Swedish Research Council, 521-2011-3527
Available from: 2018-01-30 Created: 2018-01-30 Last updated: 2018-10-31Bibliographically approved
Nilsson, A., Johansson, C., Skarp, A., Kaden, R., Engstrand, L. & Rautelin, H. (2017). Genomic and phenotypic characteristics of Swedish C. jejuni water isolates. PLoS ONE, 12(12), Article ID e0189222.
Open this publication in new window or tab >>Genomic and phenotypic characteristics of Swedish C. jejuni water isolates
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0189222Article in journal (Refereed) Published
Abstract [en]

Campylobacter jejuni is the most common cause of bacterial gastroenteritis. Major reservoirs are warm-blooded animals, poultry in particular, but Campylobacter can also be transmitted via water. In this paper, we have taken a closer look at the biology and potential virulence of C. jejuni water isolates. Seven C. jejuni isolates from incoming surface water at water plants in Sweden were characterized with whole genome sequencing and phenotypical testing. Multi locus sequence typing analysis revealed that these isolates belonged to groups known to include both common (ST48CC) and uncommon (ST1275CC, ST683, ST793 and ST8853) human pathogens. Further genomic characterization revealed that these isolates had potential for arsenic resistance (due to presence of arsB gene in all isolates), an anaerobic dimethyl sulfoxide oxidoreductase (in three isolates) and lacked the MarR-type transcriptional regulator gene rrpB (in all but one isolate) earlier shown to be involved in better survival under oxidative and aerobic stress. As putative virulence factors were concerned, there were differences between the water isolates in the presence of genes coding for cytolethal distending toxin (cdtABC), Type VI secretion system and sialylated LOS, as well as in biofilm formation. However, all isolates were motile and could adhere to and invade the human HT-29 colon cancer cell line in vitro and induce IL-8 secretion suggesting potential to infect humans. This is, to the best of our knowledge, the first study where C. jejuni water isolates have been characterized using whole genome sequencing and phenotypical assays. We found differences and shared traits among the isolates but also potential to infect humans.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-339657 (URN)10.1371/journal.pone.0189222 (DOI)000417337800098 ()29216271 (PubMedID)
Funder
Swedish Research Council Formas, 221-2012-1442
Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-03-08Bibliographically approved
Lytsy, B., Engstrand, L., Gustafsson, Å. & Kaden, R. (2017). Time to review the gold standard for genotyping vancomycin-resistant enterococci in epidemiology: Comparing whole-genome sequencing with PFGE and MLST in three suspected outbreaks in Sweden during 2013–2015. Infection, Genetics and Evolution, 54, 74-80
Open this publication in new window or tab >>Time to review the gold standard for genotyping vancomycin-resistant enterococci in epidemiology: Comparing whole-genome sequencing with PFGE and MLST in three suspected outbreaks in Sweden during 2013–2015
2017 (English)In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 54, p. 74-80Article in journal (Refereed) Published
Abstract [en]

Vancomycin-resistant enterococci (VRE) are a challenge to the health-care system regarding transmission rate and treatment of infections. VRE outbreaks have to be controlled from the first cases which means that appropriate and sensitive genotyping methods are needed.

The aim of this study was to investigate the applicability of whole genome sequencing based analysis compared to Pulsed-Field Gel Electrophoresis (PFGE) and Multi-Locus Sequence Typing (MLST) in epidemiological investigations as well as the development of a user friendly method for daily laboratory use.

Out of 14,000 VRE - screening samples, a total of 60 isolates positive for either vanA or vanB gene were isolated of which 38 were from patients with epidemiological links from three suspected outbreaks at Uppsala University Hospital. The isolates were genotypically characterised with PFGE, MLST, and WGS based core genome Average Nucleotide Identity analysis (cgANI). PFGE was compared to WGS and MLST regarding reliability, resolution, and applicability capacity.

The PFGE analysis of the 38 isolates confirmed the epidemiological investigation that three outbreaks had occurred but gave an unclear picture for the largest cluster. The WGS analysis could clearly distinguish six ANI clusters for those 38 isolates.

As result of the comparison of the investigated methods, we recommend WGS-ANI analysis for epidemiological issues with VRE. The recommended threshold for Enterococcus faecium VRE outbreak strain delineation with core genome based ANI is 98.5%.

All referred sequences of this study are available from the NCBI BioProject number PRJNA301929.

Keywords
PFGE; MLST; NGS; ANI; VRE; Cut off point WGS
National Category
Microbiology in the medical area
Research subject
Biology with specialization in Microbiology; Epidemiology
Identifiers
urn:nbn:se:uu:diva-326585 (URN)10.1016/j.meegid.2017.06.010 (DOI)000411461400010 ()28627467 (PubMedID)
Available from: 2017-07-14 Created: 2017-07-14 Last updated: 2018-01-13Bibliographically approved
Ljungdahl, M., Österberg, J., Ransjö, U., Engstrand, L. & Haglund, U. (2007). Inflammatory response in patients with malignant obstructive jaundice. Scandinavian Journal of Gastroenterology, 42(1), 94-102
Open this publication in new window or tab >>Inflammatory response in patients with malignant obstructive jaundice
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2007 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 1, p. 94-102Article in journal (Refereed) Published
Abstract [en]

Objective. Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract. Material and methods. Patients with obstructive jaundice (group HPB+) were compared with those without (HPB-). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-α, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis). Results. Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB+. The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased. Conclusions. Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.

Keywords
Apoptosis, bacterial translocation, cytokines, endotoxins, lymphocytes, obstructive jaundice, surgery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92557 (URN)10.1080/00365520600825190 (DOI)000243724800016 ()17190769 (PubMedID)
Available from: 2005-02-17 Created: 2005-02-17 Last updated: 2017-12-14Bibliographically approved
Nilsson, C., Skoglund, A., Moran, A. P., Annuk, H., Engstrand, L. & Normark, S. (2006). An enzymatic ruler modulates Lewis antigen glycosylation of Helicobacter pylori LPS during persistent infection. Proceedings of the National Academy of Sciences of the United States of America, 103(8), 2863-2868
Open this publication in new window or tab >>An enzymatic ruler modulates Lewis antigen glycosylation of Helicobacter pylori LPS during persistent infection
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2006 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 103, no 8, p. 2863-2868Article in journal (Other academic) Published
Abstract [en]

Helicobacter pylori persistently colonizes about half the human population and contributes to the development of peptic ulcer disease and gastric cancer. This organism has evolved means to structurally alter its surface characteristics to evade innate and adaptive immune responses. H. pylori produces LPS O-antigen units that can be posttranslationally fucosylated to generate Lewis antigens, structures also found on human epithelial cells. We demonstrate an extensive diversity of Lewis x and Lewis y expression in LPS O-antigen units, occurring over time and in different regions of the human stomach. Lewis expression patterns were correlated with the on/off status of the three fucosyltransferases (FucT), FutA, FutB, and FutC, which are regulated via slipped-strand mispairing in intragenic polyC tract regions of the corresponding genes. The alpha1,3-FucT, FutA and FutB, each contain a C-terminal heptad repeat region, consisting of a variable number of DD/NLRV/INY tandem repeats. Variations in the number of heptad repeats correlated to the sizes of O-antigen polymers to become decorated by fucose residues. Our data support a molecular ruler mechanism for how H. pylori varies its LPS fucosylation pattern, where one heptad repeat in the enzyme corresponds to one N-acetyl-beta-lactosamine unit in the O-antigen polysaccharide.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-77261 (URN)10.1073/pnas.0511119103 (DOI)16477004 (PubMedID)
Available from: 2006-03-13 Created: 2006-03-13 Last updated: 2017-12-14Bibliographically approved
Oh, J. D., Kling-Bäckhed, H., Giannakis, M., Engstrand, L. G. & Gordon, J. I. (2006). Interactions between gastric epithelial stem cells and Helicobacter pylori in the setting of chronic atrophic gastritis.. Curr Opin Microbiol, 9(1), 21-7
Open this publication in new window or tab >>Interactions between gastric epithelial stem cells and Helicobacter pylori in the setting of chronic atrophic gastritis.
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2006 (English)In: Curr Opin Microbiol, ISSN 1369-5274, Vol. 9, no 1, p. 21-7Article in journal (Other scientific) Published
Keywords
Carcinoid Tumor/diagnosis/*radionuclide imaging, Humans, Positron-Emission Tomography/*methods, Reproducibility of Results
Identifiers
urn:nbn:se:uu:diva-77255 (URN)16406776 (PubMedID)
Available from: 2007-03-01 Created: 2007-03-01 Last updated: 2011-01-11
Willen, R., Wanders, A. & Engstrand, L. (2006). Intestinal spirochaetosis [Letter to the editor]. Histopathology, 49(6), 658-659
Open this publication in new window or tab >>Intestinal spirochaetosis
2006 (English)In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 49, no 6, p. 658-659Article in journal, Letter (Refereed) Published
Keywords
Antibodies; Bacterial/analysis, Antigens; Bacterial/immunology, Fluorescent Antibody Technique; Indirect, Humans, Intestinal Diseases; Parasitic/*diagnosis/immunology/microbiology, Intestinal Mucosa/immunology/microbiology/*pathology, Spirochaetales/classification/immunology/*isolation & purification, Spirochaetales Infections/*diagnosis/immunology/microbiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-10573 (URN)17163854 (PubMedID)
Available from: 2007-04-05 Created: 2007-04-05 Last updated: 2017-12-11Bibliographically approved
Henriksnäs, J., Phillipson, M., Petersson, J., Engstrand, L. & Holm, L. (2005). An in vivo model for gastric physiological and pathophysiological studies in the mouse. Acta Physiologica Scandinavica, 184(2), 151-159
Open this publication in new window or tab >>An in vivo model for gastric physiological and pathophysiological studies in the mouse
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2005 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 184, no 2, p. 151-159Article in journal (Refereed) Published
Abstract [en]

Aim:  In vivo models for studying gastrointestinal physiology and pathophysiology are well established in rats. Since a number of genetically modified mice are available there is a need for reliable mouse models. The aim of this project was to develop an in vivo mouse model for gastrointestinal studies.

Methods: C57bl/6, NMRI and transgenic FVB/N (expressing human α-1,3/4-fucosyltransferase) mice were anaesthetized with isoflurane and the gastric mucosa exteriorized for intravital microscopy. Acid–base status and acid secretion were measured and blood pressure was continuously monitored. Gastric mucosal blood flow was recorded by laser-Doppler flowmetry. Mucus thickness and accumulation rate were measured with micropipettes.

Results: We have developed an in vivo mouse model for studies of the gastric mucosa. With isoflurane anaesthesia the preparation can be studied for up to 5 h with stable blood pressure and mucosal blood flow. Acid–base status agrees with results from other laboratories. Blood flow increased in both C57bl/6 and α1.3/4-FT mice in response to luminal HCl, and the mucus gel could be divided into a firmly and a loosely adherent layer, all comparable with results in the rat. However, the firmly adherent mucus layer was thinner (45 ± 2 μm), and the mucus accumulation rate lower, than in the rat. Furthermore, both basal and stimulated acid secretion showed lower outputs than in the rat.

Conclusions: This model has great potential for investigations of gastrointestinal physiology and pathophysiology and can be applied for Helicobacter pylori infection studies.

Keywords
Acid-Base Equilibrium/physiology, Acids/metabolism, Animals, Blood Flow Velocity/physiology, Gastric Mucosa/anatomy & histology/physiology, Gastrointestinal Tract/*physiology/physiopathology, Male, Mice, Mice; Inbred C57BL, Mice; Transgenic, Models; Animal, Research Support; Non-U.S. Gov't, Stomach/physiology/physiopathology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-79817 (URN)10.1111/j.1365-201X.2005.01434.x (DOI)15916675 (PubMedID)
Available from: 2007-01-26 Created: 2007-01-26 Last updated: 2017-12-14Bibliographically approved
Kivi, M., Tindberg, Y., Bengtsson, C., Engstrand, L. & Granström, M. (2005). Assessment of the cag pathogenicity island status of Helicobacter pylori infections with serology and PCR.. Clin Microbiol Infect, 11(1), 66-8
Open this publication in new window or tab >>Assessment of the cag pathogenicity island status of Helicobacter pylori infections with serology and PCR.
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2005 (English)In: Clin Microbiol Infect, ISSN 1198-743X, Vol. 11, no 1, p. 66-8Article in journal (Other scientific) Published
Keywords
Antibodies; Bacterial/*blood, Antigens; Bacterial/genetics/*immunology, Bacterial Proteins/genetics/*immunology, Comparative Study, Genomic Islands/*genetics/immunology, Helicobacter Infections/epidemiology/microbiology, Helicobacter pylori/genetics/immunology/*pathogenicity, Humans, Immunoblotting, Polymerase Chain Reaction/*methods, Research Support; Non-U.S. Gov't, Serologic Tests
Identifiers
urn:nbn:se:uu:diva-77240 (URN)15649307 (PubMedID)
Available from: 2006-06-27 Created: 2006-06-27 Last updated: 2011-01-11
Jönsson, M., Qvarnström, Y., Engstrand, L. & Swedberg, G. (2005). Clarithromycin treatment selects for persistent macrolide-resistant bacteria in throat commensal flora.. Int J Antimicrob Agents, 25(1), 68-74
Open this publication in new window or tab >>Clarithromycin treatment selects for persistent macrolide-resistant bacteria in throat commensal flora.
2005 (English)In: Int J Antimicrob Agents, ISSN 0924-8579, Vol. 25, no 1, p. 68-74Article in journal (Refereed) Published
Keywords
Anti-Bacterial Agents/administration & dosage/*pharmacology/*therapeutic use, Clarithromycin/administration & dosage/*therapeutic use, Drug Resistance; Bacterial/*drug effects/genetics, Helicobacter Infections/*drug therapy/microbiology, Helicobacter pylori/drug effects, Humans, Macrolides/administration & dosage/*pharmacology/therapeutic use, Microbial Sensitivity Tests, Neisseria/drug effects/growth & development, Pharynx/drug effects/*microbiology, Research Support; Non-U.S. Gov't, Streptococcus/*drug effects/growth & development
Identifiers
urn:nbn:se:uu:diva-68023 (URN)15620829 (PubMedID)
Available from: 2006-10-03 Created: 2006-10-03 Last updated: 2011-01-12
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