| 1. |
- Fällman, Maria, et al.
(författare)
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Resistance to phagocytosis by Yersinia
- 2002
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Ingår i: International Journal of Medical Microbiology. - : Urban & Fischer. - 1438-4221 .- 1618-0607. ; 291:6-7, s. 501-509
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Tidskriftsartikel (refereegranskat)abstract
- Enteropathogenic species of the genus Yersinia penetrate the intestinal epithelium and then spread to the lymphatic system, where they proliferate extracellularly. At this location, most other bacteria are effectively ingested and destroyed by the resident phagocytes. Yersinia, on the other hand binds to receptors on the external surface of phagocytes, and from this location it blocks the capacity of these cells to exert their phagocytic function via different receptors. The mechanism behind the resistance to phagocytosis involves the essential virulence factor YopH, a protein tyrosine phosphatase that is translocated into interacting target cells via a type III secretion machinery. YopH disrupts peripheral focal complexes of host cells, seen as a rounding up of infected cells. The focal complex proteins that are dephosphorylated by YopH are focal adhesion kinase and Crk-associated substrate, the latter of which is a common substrate in both professional and non-professional phagocytes. In macrophages additional substrates have been found, the Fyn-binding/SLP-76-associated protein and SKAP-HOM. Phagocytosis is a rapid process that is activated when the bacterium interacts with the phagocyte. Consequently, the effect exerted by a microbe to block this process has to be rapid and precise. This review deals with the mechanisms involved in impeding uptake as well as with the role of the YopH substrates and focal complex structures in normal cell function.
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| 2. |
- Kolak, M., et al.
(författare)
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Molecular typing of the bacterial flora in sputum of cystic fibrosis patients
- 2003
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 293:4, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in therapy, lower airway infections remain the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Bacterial colonisation of the lower airways in CF is limited to a few bacterial species, commonly Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae. Burkholderia cepacia colonisation is much rarer, but it has been thought to be associated with more advanced lung disease and increased mortality. A rapid characterisation of the bacterial flora in sputum of CF patients is of great importance for proper treatment. The aim of this study was to establish bacterial profiles and to identify pathogenic bacteria in respiratory specimens by means of molecular methods including temporal temperature gradient gel electrophoresis (TTGE) and DNA sequencing of PCR amplicons derived from 16S rDNA variable V3 and V6 regions. Sputa of 13 CF patients (7 males/6 females, age 19-59 years) collected at the Stockholm CF centre were analysed. TTGE revealed the presence of complex bacterial profiles in all samples. The V3 and V6 PCR amplicons were cloned and sequenced by real-time DNA PyrosequencingTM. DNA from Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa, respectively, was identified together with sequences from normal oral cavity flora. The results were in reasonable agreement with those obtained by conventional bacterial culture, considering that only known CF pathogens are included in routine reports. However, the methodology seems too elaborate to be introduced into daily routine.
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| 3. |
- Popp, A, et al.
(författare)
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Signal transduction pathways induced by virulence factors of Neisseria gonorrhoeae
- 2001
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 291:4, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- The obligate human pathogen Neisseria gonorrhoeae infects a variety of human tissues. In recent years, several host cell receptors for the major bacterial adhesins have been identified. While the knowledge of the molecular mechanism of colonisation has helped to understand special aspects of the infection, like the explicit tropism of gonococci for human tissues, the long-term consequences of engaging these receptors are still unknown. A variety of signalling pathways initiated by the activated receptors and by bacterial proteins transferred to the infected cell have been defined which include lipid second messenger, protein kinases, proteases and GTPases. These pathways control important steps of the infection, such as tight adhesion and invasion, the induction of cytokine release, and apoptosis. The detailed knowledge of bacteria-induced signalling pathways could allow the design of new therapeutic approaches which might be advantageous over the classical antibiotics therapy.
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| 4. |
- Ståhl, Stefan, et al.
(författare)
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Staphylococcal surface display and its applications
- 2000
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 290:7, s. 571-577
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Forskningsöversikt (refereegranskat)abstract
- Novel surface proteins can be introduced onto the bacterial cell surface by recombinant means. Here, we describe the development of such display systems for two food-grade bacteria, Staphylococcus carnosus and Staphylococcus xylosus, and present how such engineered bacteria can be used in different applications. A study will be described in which such staphylococci were employed as vaccine delivery vehicles to elicit protective antibody responses to respiratory syncytial virus (RSV). The use of surface-engineered staphylococci as novel microbial biocatalysts, as a new type of whole-cell diagnostic devices or for adsorption of metal ions with potential environmental or biosensor applications, will also be discussed.
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| 5. |
- Aili, Margareta, et al.
(författare)
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Regulation of Yersinia Yop-effector delivery by translocated YopE
- 2008
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Ingår i: International Journal of Medical Microbiology. - : Elsevier. - 1438-4221 .- 1618-0607. ; 298:3-4, s. 183-192
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial pathogen Yersinia pseudotuberculosis uses a type III secretion (T3S) system to translocate Yop effectors into eukaryotic cells. Effectors are thought to gain access to the cytosol via pores formed in the host cell plasma membrane. Translocated YopE can modulate this pore formation through its GTPase-activating protein (GAP) activity. In this study, we analysed the role of translocated YopE and all the other known Yop effectors in the regulation of effector translocation. Elevated levels of Yop effector translocation into HeLa cells occurred by YopE-defective strains, but not those defective for other Yop effectors. Only Yersinia devoid of YopK exhibits a similar hyper-translocation phenotype. Since both yopK and yopE mutants also failed to down-regulate Yop synthesis in the presence of eukaryotic cells, these data imply that translocated YopE specifically regulates subsequent effector translocation by Yersinia through at least one mechanism that involves YopK. We suggest that the GAP activity of YopE might be working as an intra-cellular probe measuring the amount of protein translocated by Yersinia during infection. This may be a general feature of T3S-associated GAP proteins, since two homologues from Pseudomonas aeruginosa, exoenzyme S (ExoS) and exoenzyme T (ExoT), can complement the hyper-translocation phenotypes of the yopE GAP mutant.
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| 6. |
- Asmat, Tauseef M, et al.
(författare)
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Endocytosis of Streptococcus pneumoniae via the polymeric immunoglobulin receptor of epithelial cells relies on clathrin and caveolin dependent mechanisms.
- 2014
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 304:8, s. 1233-1246
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Tidskriftsartikel (refereegranskat)abstract
- Colonization of Streptococcus pneumoniae (pneumococci) is a prerequisite for bacterial dissemination and their capability to enter the bloodstream. Pneumococci have evolved various successful strategies to colonize the mucosal epithelial barrier of humans. A pivotal mechanism of host cell invasion implicated with invasive diseases is promoted by the interaction of pneumococcal PspC with the polymeric Ig-receptor (pIgR). However, the mechanism(s) of pneumococcal endocytosis and the intracellular route of pneumococci upon uptake by the PspC-pIgR-interaction are not known. Here, we demonstrate by using a combination of pharmacological inhibitors and genetics interference approaches the involvement of active dynamin-dependent caveolae and clathrin-coated vesicles for pneumococcal uptake via the PspC-pIgR mechanism. Depleting cholesterol from host cell membranes and disruption of lipid microdomains impaired pneumococcal internalization. Moreover, chemical inhibition of clathrin or functional inactivation of dynamin, caveolae or clathrin by RNA interference significantly affected pneumococcal internalization suggesting that clathrin-mediated endocytosis (CME) and caveolae are involved in the bacterial uptake process. Confocal fluorescence microscopy of pIgR-expressing epithelial cells infected with pneumococci or heterologous Lactococcus lactis expressing PspC demonstrated bacterial co-localization with fluorescent-tagged clathrin and early as well as recycling or late endosomal markers such as Lamp1, Rab5, Rab4, and Rab7, respectively. In conclusion these data suggest that PspC-promoted uptake is mediated by both CME and caveolae. After endocytosis pneumococci are routed via the endocytic pathway into early endosomes and are then sorted into recycling or late endosomes, which can result in pneumococcal killing in phagolysosomes or transcytosis via recycling endosomes.
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| 7. |
- Baranwal, Gaurav, et al.
(författare)
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Impact of cell wall peptidoglycan O-acetylation on the pathogenesis of Staphylococcus aureus in septic arthritis.
- 2017
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Ingår i: International journal of medical microbiology : IJMM. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 307:7, s. 388-397
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus (S. aureus) is one of the most common pathogen causing septic arthritis. To colonize the joints and establish septic arthritis this bacterium needs to resist the host innate immune responses. Lysozyme secreted by neutrophils and macrophages is an important defense protein present in the joint synovial fluids. S. aureus is known to be resistant to lysozyme due to its peptidoglycan modification by O-acetylation of N-acetyl muramic acid. In this study we have investigated the role of O-acetylated peptidoglycan in septic arthritis. Using mouse models for both local and hematogenous S. aureus arthritis we compared the onset and progress of the disease induced by O-acetyl transferase mutant and the parenteral wild type SA113 strain. The disease progression was assessed by observing the clinical parameters including body weight, arthritis, and functionality of the affected limbs. Further X-ray and histopathological examinations were performed to monitor the synovitis and bone damage. In local S. aureus arthritis model, mice inoculated with the ΔoatA strain developed milder disease (in terms of knee swelling, motor and movement functionality) compared to mice inoculated with the wild type SA113 strain. X-ray and histopathological data revealed that ΔoatA infected mice knee joints had significantly lesser joint destruction, which was accompanied by reduced bacterial load in knee joints. Similarly, in hematogenous S. aureus arthritis model, ΔoatA mutant strain induced significantly less severe clinical septic arthritis compared to its parental strain, which is in accordance with radiological findings. Our data indicate that peptidoglycan O-acetylation plays an important role in S. aureus mediated septic arthritis.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Edvinsson, Marie, et al.
(författare)
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Chlamydophila pneumoniae changes iron homeostasis in infected tissues
- 2008
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 298:7-8, s. 635-44
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Tidskriftsartikel (refereegranskat)abstract
- Many bacteria, including Chlamydophila pneumoniae (C. pneumoniae), are dependent on iron (Fe) for their growth. However, it is not known whether bacterial infections affect gastrointestinal uptake and uptake of trace elements in infected tissues. A human C. pneumoniae strain adapted to C57BL/6J mice was used to study hepcidin gene expression in the liver and divalent metal transporter 1 (DMT1) content in the liver and intestine and whether Fe is concomitantly changed in serum, liver, and intestine. The copper/zinc (Cu/Zn) ratio in the serum was used as a marker for infection. Bacterial DNA, mRNA, and hepcidin were measured by real-time PCR, DMT1 by Western blot, and trace elements by ICP-MS on days 2, 5, and 8 of the infection. C. pneumoniae DNA was found in the liver on all days but the number of viable bacteria peaked on day 8. Hepcidin expression increased on days 2 and 5, whereas DMT1 content in the liver increased on day 8. Fe decreased in serum, increased in the liver but was not changed in the intestine during the disease. In the serum, the Cu/Zn ratio peaked on day 5. The peak of viable bacteria in the liver was associated with increased DMT1 and Fe contents and increased hepcidin expression, but this did not affect intestinal Fe uptake. Thus, growth of C. pneumoniae in tissues parallels a redistribution of Fe to those tissues resulting in a changed body homeostasis of Fe.
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| 12. |
- Ellström, Patrik, et al.
(författare)
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Characterization of clinical Campylobacter jejuni isolates with special emphasis on lipooligosaccharide locus class, putative virulence factors and host response
- 2013
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 303:3, s. 134-139
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have indicated a role of the lipooligosaccharide (LOS) of Campylobacter jejuni in the severe neurological Guillain Barre syndrome, as well as in development of more severe symptoms of acute enteritis. We evaluated the role of the LOS locus class in C jejuni infection among 163 enteritis patients. The prevalence of LOS locus classes differed according to the origin of the isolates. Furthermore, LOS locus classes A and B were significantly associated with susceptibility or resistance to ciprofloxacin and doxycycline. However, our results do not corroborate earlier findings that isolates with potential to sialylate LOS might be associated with more severe symptoms of enteritis. Instead, in an infection model, such isolates gave weaker epithelial IL-8 responses than nonsialylated isolates. Absence of the iron transport protein encoded by the gene ceuE as well as the putative fucose permease gene cj0486 was associated with increased in vitro IL-8 secretion.
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| 13. |
- Engström, Patrik, et al.
(författare)
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Expansion of the Chlamydia trachomatis inclusion does not require bacterial replication
- 2015
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 305:3, s. 378-382
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis replication takes place inside of a host cell, exclusively within a vacuole known as the inclusion. During an infection, the inclusion expands to accommodate the increasing numbers of C. trachomatis. However, whether inclusion expansion requires bacterial replication and/or de novo protein synthesis has not been previously investigated in detail. Therefore, using a chemical biology approach, we herein investigated C. trachomatis inclusion expansion under varying conditions in vitro. Under normal cell culture conditions, inclusion expansion correlated with C trachomatis replication. When bacterial replication was inhibited using KSK120: an inhibitor that targets C. trachomatis glucose metabolism, inclusions expanded even in the absence of bacterial replication. In contrast, when bacterial protein synthesis was inhibited using chloramphenicol, expansion of inclusions was blocked. Together, these data suggest that de novo protein synthesis is necessary, whereas bacterial replication is dispensable for C trachomatis inclusion expansion. (C) 2015 The Authors. Published by Elsevier GmbH.
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| 14. |
- Eriksson, Per-Olof, et al.
(författare)
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Spontaneous development of otitis media in plasminogen-deficient mice
- 2006
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 296:7, s. 501-509
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory conditions of the ear, otitis media, are one of the most common disease entities in children. In this study, the role of the plasminogen (plg)/plasmin system for the spontaneous development of chronic otitis media was investigated by the analysis of plg-deficient mice. Whereas essentially all of the wild-type control mice kept a healthy status of the middle ear, all the plg-deficient mice gradually developed chronic otitis media with various degrees of inflammatory changes during an 18-week observation period. Five bacterial strains were identified in materials obtained from the middle ear cavities of six plg-deficient mice. Morphological studies revealed the formation of an amorphous mass tissue and inflammatory changes in the middle ears of plg-deficient mice. Immunohistochemical studies further indicate a mass infiltration of neutrophils and macrophages as well as the presence of T and B cells in the middle ear mucosa of these mice. Extensive fibrin deposition and an abnormal keratin formation were also observed in the tympanic membrane, the middle ear cavity and external ear canal in these mice. These results suggest that plg plays an essential role in protecting against the spontaneous development of chronic otitis media. Our findings also suggest the possibility of using plg for clinical therapy of certain types of otitis media.
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| 15. |
- Fulton, Kelly M., et al.
(författare)
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Immunoproteomic analysis of the human antibody response to natural tularemia infection with Type A or Type B strains or LVS vaccination
- 2011
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 301:7, s. 591-601
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is pathogenic for many mammalian species including humans, causing a spectrum of diseases called tularemia. The highly virulent Type A strains have associated mortality rates of up to 60% if inhaled. An attenuated live vaccine strain (LVS) is the only vaccine to show efficacy in humans, but suffers several barriers to licensure, including the absence of a correlate of protection. An immunoproteomics approach was used to survey the repertoire of antibodies in sera from individuals who had contracted tularemia during two outbreaks and individuals from two geographical areas who had been vaccinated with NDBR Lot 11 or Lot 17 LVS. These data showed a large overlap in the antibodies generated in response to tularemia infection or LVS vaccination. A total of seven proteins were observed to be reactive with 60% or more sera from vaccinees and convalescents. A further four proteins were recognised by 30-60% of the sera screened. These proteins have the potential to serve as markers of vaccination or candidates for subunit vaccines. Crown Copyright (C) 2011 Published by Elsevier GmbH. All rights reserved.
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| 16. |
- Gustafsson, Erik, et al.
(författare)
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Mathematical modelling of the regulation of spa (protein A) transcription in Staphylococcus aureus.
- 2009
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Ingår i: International journal of medical microbiology : IJMM. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 299:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- In the present work a general systems biology approach has been used to study the complex regulatory network controlling the transcription of the spa gene, encoding protein A, a major surface protein and an important virulence factor of Staphylococcus aureus. A valid mathematical model could be formulated using parameter values, which were fitted to quantitative Northern blot data from various S. aureus regulatory mutants using a gradient search method. The model could correctly predict spa expression levels in 4 different regulatory mutants not included in the parameter value search, and in 2 other S. aureus strains, SH1000 and UAMS-1. The mathematical model revealed that sarA and sarS seem to balance each other in a way that when the activating impact of sarS is small, e.g. in the wild-type, the repressive impact of sarA is small, while in an agr-deficient background, when the impact of sarS is maximal, the repressive impact of sarA is close to its maximum. Furthermore, the model revealed that Rot and SarS act synergistically to stimulate spa expression, something that was not obvious from experimental data. We believe that this mathematical model can be used to evaluate the significance of other putative interactions in the regulatory network governing spa transcription.
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| 17. |
- Hellmark, Bengt, 1971-, et al.
(författare)
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Comparison of Staphylococcus epidermidis isolated from prosthetic joint infections and commensal isolates in regard to antibiotic susceptibility, agr type, biofilm production, and epidemiology
- 2013
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Ingår i: International Journal of Medical Microbiology. - Jena, Germany : Elsevier. - 1438-4221 .- 1618-0607. ; 303:1, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus epidermidis is the predominant bacterial species in the normal flora of the human skin and superficial mucosal membranes. However, it has also emerged as the most important pathogen in infections related to foreign-body materials, such as prosthetic joints and heart valves. The aims of this study were to characterise S. epidermidis isolated from prosthetic joint infections (PJI; n = 61) and commensal isolates from healthy individuals (n = 24) in regard to antimicrobial sensitivity, agr type, hid gene presence, biofllm production including presence of ica and aap genes involved in the biofilm formation process and epidemiology using both phenotypic (the PhenePlate-system) and genotypic [multilocus sequence typing (MLST)] methods. Among the PJI isolates, the majority (67%) were multidrug-resistant. Two major clusters of PJI isolates could be identified; 44% belonged to MLST sequence type (ST) 2, all but one were of agr type 1, and 31% were assigned ST215 and were of agr type 3. Of the commensal isolates, only one isolate was multidrug-resistant, and they were more molecular epidemiologically diverse with mainly MLST singletons and a maximum of 3 isolates assigned to the identical ST. Biofilm production was detected in 41% of the PJI isolates and 58% of the commensal isolates, with the aap gene (95%) more frequently detected than the ica genes (62%) in the biofilm-positive isolates. In conclusion, S. epidermidis isolated from PJIs and commensal isolates differed regarding antimicrobial sensitivity and molecular epidemiological typing using MLST, but not substantially in the distribution of agr types, biofilm production, or the presence of ica and aap genes.
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| 18. |
- Hällgren, Anita, et al.
(författare)
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Molecular detection of aggregation substance, enterococcal surface protein, and cytolysin genes and in vitro adhesion to urinary catheters of Enterococcus faecalis and E. faecium of clinical origin
- 2009
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 299:5, s. 323-332
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that nosocomial enterococci might have virulence factors that enhance their ability to colonise hospitalised patients. The objectives of this study were to investigate the prevalence of genes encoding 3 virulence factors: aggregation substance (asa1), enterococcal surface protein (esp), and 5 genes within the cytolysin operon (cylA, cylB, cylM, cylL(L), cylL(S)) and cytolysin production in 115 enterococcal clinical isolates (21 Enterococcus faecium and 94 E. faecalis). Adhesion to siliconized latex urinary catheters in relation to presence of esp was analysed in a subset of isolates. The isolates were previously characterised by pulsed-field gel electrophoresis (PFGE). esp was the only virulence gene found in E. faecium. It was found in 71% of the 21 E. faecium isolates. asa1, esp, and the cyl operon were found in 79%, 73% and 13% respectively, of the 94 E. faecalis isolates. There was a complete agreement between presence of the cyl operon and phenotypic cytolysin production. Isolates belonging to a cluster of genetically related isolates carried esp and asa1 more often when compared to unique isolates. No difference was found with respect to cyl genes. E. faecalis isolates adhered with higher bacterial densities than E. faecium. E. faecalis isolates within the same PFGE cluster adhered with similar bacterial densities, but there was no association between adhesion and the presence of esp when isolates within the same cluster were compared. In conclusion, E. faecalis isolates with high-level gentamicin resistance (HLGR) belonging to clusters of genetically related isolates widely distributed in Swedish hospitals, were likely to carry both esp and asa1. Adhesion was not affected by esp.
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| 19. |
- Joffre, Enrique, et al.
(författare)
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Identification of new heat-stable (STa) enterotoxin allele variants produced by human enterotoxigenic Escherichia coli (ETEC)
- 2016
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 306:7, s. 586-594
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Tidskriftsartikel (refereegranskat)abstract
- We describe natural variants of the heat stable toxin (STa) produced by enterotoxigenic Escherichia coli (ETEC) isolates collected worldwide. Previous studies of ETEC isolated from human diarrheal cases have reported the existence of three natural STa gene variants estA1, estA2 and estA3/4 where the first variant encodes STp (porcine, bovine, and human origin) and the two latter ones encode STh (human origin). We identified STa sequences by BLASTn and profiled ST amino acid polymorphisms in a collection of 118 clinical ETEC isolates from children and adults from Asia, Africa and, Latin America that were characterized by whole genome sequencing. Three novel variants of STp and STh were found and designated STa5 and STa6, and STa7, respectively. Presence of glucose significantly decreased the production of STh and STp toxin variants (p < 0.05) as well as downregulated the gene expression (STh: p < 0.001, STp: p < 0.05). We found that the ETEC isolates producing the most common STp variant, STa5, co-expressed coli surface antigen CS6 and was significantly associated with disease in adults in this data set (p < 0.001). Expression of mature STa5 peptide as well as gene expression of tolC, involved in ST secretion, increased in response to bile (p < 0.05). ETEC expressing the common STh variant STa3/4 was associated with disease in children (p < 0.05). The crp gene, that positively regulate estA3/4 encoding STa3/4, and estA3/4 itself had decreased transcriptional levels in presence of bile. Since bile levels in the intestine are lower in children than adults, these results may suggest differences in pathogenicity of ETEC in children and adult populations. (C) 2016 The Author(s). Published by Elsevier GmbH.
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| 20. |
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| 21. |
- Kelk, Peyman, 1976-, et al.
(författare)
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IL-1beta secretion induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans is mainly caused by the leukotoxin
- 2008
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 298:5/6, s. 529-541
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Tidskriftsartikel (refereegranskat)abstract
- Aggregatibacter (Actinobacillus) actinomycetemcomitans forms a leukotoxin that selectively lyses primate neutrophils, monocytes and triggers apoptosis in promyeloic cells and degranulation of human neutrophils. Recently, we showed that the leukotoxin causes activation of caspase-1 and abundant secretion of bio-active IL-1beta from human macrophages. In this study, we show that high levels of IL-beta correlated with a high proportion of A. actinomycetemcomitans in clinical samples from a patient with aggressive periodontitis. To determine the relative contribution of leukotoxin to the overall bacteria-induced IL-1beta secretion, macrophages were isolated from peripheral blood and exposed to different concentrations of live A. actinomycetemcomitans strains with either no, low or high production of leukotoxin. Cell lysis and levels of IL-1beta, IL-6, TNF-alpha and caspase-1 were measured by ELISA and flow cytometry. Leukotoxin was the predominant cause of IL-1beta secretion from macrophages, even in the A. actinomycetemcomitans strain with low leukotoxin production. Macrophages exposed to non-leukotoxic bacteria accumulated cytosolic pro-IL-1beta, which was secreted by a secondary exposure to leukotoxic bacteria. In conclusion, the present study shows for the first time that A. actinomycetemcomitans-induced IL-1beta secretion from human macrophages in vitro is mainly caused by leukotoxin.
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| 22. |
- Knabl, Ludwig, et al.
(författare)
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Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets
- 2018
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 308:7, s. 969-976
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli-induced hemolytic uremic syndrome (eHUS) is a life-threatening complication of infection with Shiga toxin (Stx), in particular Stx2a-producing Escherichia coli. Enhanced coagulation activation with formation of microthrombi seems to be a key event in development of eHUS. Platelet activation has been postulated as a possible, but controversially debated mechanism. The present study investigated the effect of Stx2a on plasmatic coagulation and platelets. Binding studies were initially performed with ELISA and co-immunoprecipitation and supported by quartz crystal microbalance with dissipation monitoring (QCM-D). Antithrombin (AT) activity was measured using the automated BCS XP (R) system. ROTEM (R) was used for functional coagulation testing. Platelet binding and activation was studied with FACS and light-transmission aggregometry. We found binding of Stx2a to AT, an important inhibitor of blood coagulation, but only a mild albeit significant reduction of AT activity against FXa in the presence of Stx2a. QCM-D analysis also showed binding of Stx2a to heparin and an impaired binding of AT to Stx2a-bound heparin. ROTEM (R) using Stx2a-treated platelet-poor plasma revealed a significant, but only moderate shortening of clotting time. Neither binding nor activation of platelets by Stx2a could be demonstrated. In summary, data of this study suggest that Stx2a binds to AT, but does not induce major effects on plasmatic coagulation. In addition, no interaction with platelets occurred. The well-known non-beneficial administration of heparin in eHUS patients could be explained by the interaction of Stx2a with heparin.
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| 23. |
- Liu, Hui, et al.
(författare)
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Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model
- 2015
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 305:3, s. 392-403
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori from different individuals exhibits substantial genetic diversity. However, the kinetics of bacterial diversification after infection with a single strain is poorly understood. We investigated evolution of H. pylori following long-term infection in the primate stomach; Rhesus macaques were infected with H. pylori strain USU101 and then followed for 10 years. H. pylori was regularly cultured from biopsies, and single colony isolates were analyzed. At 1-year, DNA fingerprinting showed that all output isolates were identical to the input strain; however, at 5-years, different H. pylori fingerprints were observed. Microarray-based comparative genomic hybridization revealed that long term persistence of USU101 in the macaque stomach was associated with specific whole gene changes. Further detailed investigation showed that levels of the BabA protein were dramatically reduced within weeks of infection. The molecular mechanisms behind this reduction were shown to include phase variation and gene loss via intragenomic rearrangement, suggesting strong selective pressure against BabA expression in the macaque model. Notably, although there is apparently strong selective pressure against babA, babA is required for establishment of infection in this model as a strain in which babA was deleted was unable to colonize experimentally infected macaques.
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| 24. |
- Lönnermark, Elisabeth, 1965, et al.
(författare)
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Oral and faecal lactobacilli and their expression of mannose-specific adhesins in individuals with and without IgA deficiency
- 2012
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 302:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Lactobacilli are present in the intestine and oral cavity of most adults. Secretory IgA in mucosal secretions may provide carbohydrate receptors for bacterial adhesins. Here, oral and faecal samples from 33 IgA-deficient individuals and 34 controls were cultured for lactobacilli, which were identified using species-specific PCR or partial 165 rDNA sequencing and tested for expression of mannose-specific adhesins. Lactobacilli were found in the oral cavity of 76% of IgA-deficient and 85% of control individuals. Lactobacillus paracasei and Lactobacillus gasseri dominated in both groups. Lactobacillus fermentum was less common in IgA-deficient individuals than in controls (p = 0.0055) and Lactobacillus salivarius was less common in symptomatic than in healthy IgA-deficient individuals (p = 0.0051). Faecal samples yielded lactobacilli in most individuals. L. paracasei was most frequent, followed by L. gasseri and Lactobacillus plantarum. Mannose-specific adhesins were expressed more frequently by oral than by faecal isolates (p = 0.032) and oral isolates adhered in higher numbers than faecal isolates (46 vs. 14 bacteria/cell, p = 0.0038). Faecal isolates from IgA-deficient individuals more frequently expressed mannose-specific adhesins than faecal isolates from controls (p = 0.039). Mannose-specific adhesins may be a colonisation factor in the oral cavity, and the presence of secretory IgA may modify adhesin expression. However, secretory IgA seems to have little influence on Lactobacillus species distribution. (C) 2011 Elsevier GmbH. All rights reserved.
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| 25. |
- Mabbett, Amanda N., et al.
(författare)
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Virulence properties of asymptomatic bacteriuria Escherichia coli
- 2009
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 299:1, s. 53-63
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Tidskriftsartikel (refereegranskat)abstract
- In asymptomatic bacteriuria (ABU), bacteria colonize the urinary tract without provoking symptoms. Here, we compared the virulence properties of a collection of ABU Escherichia coli strains to cystitis and pyelonephritis strains. Specific urinary tract infection (UTI)-associated virulence genes, hemagglutination characteristics, siderophore production, hemolysis, biofilm formation, and the ability of strains to adhere to and induce cytokine responses in epithelial cells were analyzed. ABU strains were phylogenetically related to strains that cause symptomatic UTI. However, the virulence properties of the ABU strains were variable and dependent on a combination of genotypic and phenotypic factors. Most ABU strains adhered poorly to epithelial cells; however, we also identified a subgroup of strongly adherent strains that were unable to stimulate an epithelial cell IL-6 cytokine response. Poor immune activation may represent one mechanism whereby ABU E coli evade immune detection after the establishment of bacteriuria. (C) 2008 Elsevier GmbH. All rights reserved.
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