| 1. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications
- 2003
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Ingår i: Microbes Infect. - 1286-4579 .- 1769-714X. ; 5:12, s. 1057-63
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Tidskriftsartikel (refereegranskat)abstract
- Cells of the mucosal lining are the first to encounter invading bacteria during infection, and as such, they have developed numerous ways of detecting microbial intruders. Recently, we showed that epithelial cells recognize lipopolysaccharide (LPS) through the CD14-Toll-like receptor (TLR)-4 complex. Here, we identify the substructures of LPS that are recognized by the TLR4 receptor complex. In contrast to lipid A, the O-antigen does not mediate an inflammatory response; rather it interferes with the lipid A recognition. An Escherichia coli strain genetically modified to express penta-acylated lipid A not only showed reduced immunogenicity, but was also found to inhibit pro-inflammatory signalling induced by wild-type E. coli (hexa-acylated lipid A) as well as LPS from other bacteria of the Enterobacteriaceae family. Furthermore, penta-acylated LPS from Pseudomonas aeruginosa acted as an antagonist to hexa-acylated E. coli LPS, as did E. coli, as shown by its inhibitory effect on IL-8 production in stimulated cells. Hypo-acylated lipid A, such as that of P. aeruginosa, is found in several species within the gut microflora as well as in several bacteria causing chronic infections. Thus, our results suggest that the composition of the microflora may be important in modulating pro-inflammatory signalling in epithelial cells under normal as well as pathologic conditions.
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| 2. |
- Verdrengh, M, et al.
(författare)
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Integrin-associated protein (IAP)-deficient mice are less susceptible to developing Staphylococcus aureus induced arthritis
- 1999
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Ingår i: Microbes and infection. - 1286-4579 .- 1769-714X. ; 1:10, s. 745-751
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Tidskriftsartikel (refereegranskat)abstract
- The integrin-associated protein (IAP) has been shown to function in a signaling complex with β3 integrins, influencing the migration of phagocytic cells into inflamed tissues. We have previously shown that gene-targeted mice deficient for IAP succumbed to peritonitis when inoculated with Gram-negative bacteria. The aim of this study was to assess the role of IAP in our recently established model of haematogenously induced Staphylococcus aureus septicaemia and arthritis. In this model, neutrophils play a crucial role in the early phase of the infection. Mice lacking IAP and congenic controls were intravenously inoculated with S. aureus LS-1. The IAP-/- mice were resistant to developing clinical signs of arthritis compared with their IAP-expressing littermates. The clinical findings were corroborated by histopathological evaluation indicating that the IAP-/- mice had less cartilage and bone destruction in the joints. We believe that a delayed migration of leukocytes into the joints of mice lacking IAP expression leads to decreased susceptibility to develop S. aureus-induced arthritis.
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| 3. |
- Ahrné, Siv, et al.
(författare)
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Lactobacilli in the intestinal microbiota of Swedish infants
- 2005
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 7:11-12, s. 1256-62
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Tidskriftsartikel (refereegranskat)abstract
- Lactobacillus colonisation was examined in 112 Swedish infants. Faecal samples obtained at 1, 2, 4 and 8 weeks and at 6, 12 and 18 months of age were cultivated quantitatively on Rogosa agar. Lactobacilli were speciated by PCR and typed to the strain level by randomly amplified polymorphic DNA (RAPD). Lactobacilli reached a peak at 6 months when 45% of the infants were colonised. L. rhamnosus and L. gasseri were the most common species in this period. Colonisation by lactobacilli in general (P < 0.01) and L. rhamnosus in particular (P < 0.05) was more common in breast-fed than in weaned infants at 6 months of age. Lactobacillus isolation reached a nadir of 17% by 12 months (P < 0.0001), but increased to 31% by 18 months of age P < 0.05). The food-related species L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii dominated in this second phase. A single strain persisted for at least 3 weeks in 17% of the infants during the first 6 months, most commonly L. rhamnosus. Lactobacillus population counts in colonised infants increased from 10(6.4) cfu/g at 1 week to 10(8.8) cfu/g at 6 months, and then dropped to 10(5.4) cfu/g faeces at 12 months of age. Lactobacillus colonisation was not significantly related to delivery mode, or to presence of siblings or pets in the household. Our results suggest that certain Lactobacillus species, especially L. rhamnosus, thrive in the intestinal flora of breast-fed infants. After weaning they are replaced by other Lactobacillus species of types found in food.
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| 4. |
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| 6. |
- Bereczky, Sándor, et al.
(författare)
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Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population
- 2007
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 9:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
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| 7. |
- Berglund, Carolina, et al.
(författare)
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The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus
- 2008
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Ingår i: Microbes and infection. - Paris : Elsevier. - 1286-4579 .- 1769-714X. ; 10:8, s. 878-884
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Methicillin-resistant Staphylococcus aureus isolated in the community (CA-MRSA) have been reported to carry the loci for Panton Valentine leukocidin (PVL) in high frequency. CA-MRSA in Orebro County, Sweden, constitutes at least 50% of MRSA and the PVL locus is detected in as many as 66% of these CA-MRSA isolates. The aim of this study was to characterize PVL-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus by molecular methods, to determine the nucleotide sequence of lukS-PV and lukF-PV in S. aureus isolates of different origins, and to investigate the biological consequence of variations occurring in the genes. The PVL-positive MRSA investigated were composed of six different STs (ST8, 36, 80, 152, 154, and 256). Six additional STs (ST5, 22, 25, 30, 88, and 567) were detected when investigating PVL-positive methicillin-susceptible S. aureus with MLST. Despite the different genetic origins of the isolates analyzed, the PVL genes were well conserved and only one mutation was non-synonymous. Evaluation of the consequence of this mutation showed that the mutated toxin and wild-type toxin had comparable biological activity on human polymorphonuclear cells.
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| 8. |
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| 9. |
- Charpentier, E, et al.
(författare)
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Mechanisms of antibiotic resistance and tolerance in Streptococcus pneumoniae.
- 2000
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Ingår i: Microbes and infection. - 1286-4579 .- 1769-714X. ; 2:15, s. 1855-64
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae is a major pathogen causing potentially life-threatening community-acquired diseases in both the developed and developing world. Since 1967, there has been a dramatic increase in the incidence of penicillin-resistant and multiply antibiotic-resistant pneumococci worldwide. Prevention of access of the antibiotic to the target, inactivation of the antibiotic and alteration of the target are mechanisms that S. pneumoniae has developed to resist antibiotics. Recent studies on antibiotic-tolerant pneumococcal mutants permitted development of a novel model for the control of bacterial cell death.
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| 10. |
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