1. |
- Nilson, Bo, et al.
(författare)
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Structure and stability of protein H and the M1 protein from Streptococcus pyogenes. Implications for other surface proteins of gram-positive bacteria
- 1995
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 34:41, s. 13688-13698
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Tidskriftsartikel (refereegranskat)abstract
- M proteins and other members of the M protein family, expressed on the surface of Streptococcus pyogenes, bind host proteins such as immunoglobulins, albumin, and fibrinogen. Protein H and the M1 protein are expressed by adjacent genes and both belong to the M protein family. In this work, the structure and stability of these two proteins have been investigated. As judged from sequence analysis and circular dichroism spectroscopy, the proteins are almost entirely in an alpha-helix conformation. The amino acids are arranged in a seven-residue (heptad) repeat pattern along the greater part of the proteins. These observations support the previously accepted model of M proteins as coiled-coil dimers. However, it was also found that the structures of both proteins were thermally unstable; i.e., the content of helix conformation was greatly reduced at 37 degrees C as compared to 25 degrees C or below. Together with previous findings that these proteins appear as monomers at 37 degrees C and dimers at low temperatures, the results suggest that the coiled-coil dimers are unfolded at 37 degrees C. The heptad patterns of protein H and the M1 protein showed a nonoptimal distribution of residues expected for a coiled-coil conformation. This is a possible explanation for the low thermal stability of the proteins. It was also demonstrated that the proteins were stabilized in the presence of the ligands IgG and/or albumin. Protein H and M1 protein show a high degree of sequence similarity in their C-terminal regions, and a fragment from this region displayed a high content of helix conformation, whereas fragments from the nonsimilar N-terminal parts did not adopt any stable folded structure. Thus, the C-terminal parts, which are conserved within the M protein family, may constitute a framework for the formation of the parallel helical coiled-coil structure, and we propose that the less stable N-terminal part may also participate in antiparallel interaction with M proteins on adjacent bacteria. The results suggest that temperature fluctuations in the environment could change the properties of bacterial surface proteins, thereby affecting the molecular interactions between the bacterium and its host.
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2. |
- Axelsson, Carolina, et al.
(författare)
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Rapid detection of antibiotic resistance in positive blood cultures by MALDI-TOF MS and an automated and optimized MBT-ASTRA protocol for Escherichia coli and Klebsiella pneumoniae
- 2020
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 52:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: For fast and effective antibiotic therapy of serious infections like sepsis, it is crucial with rapid information about antibiotic susceptibility, especially in a time when the number of infections caused by multi resistant bacteria has escalated in the world. Methods: Here, we have used a semi-quantitative MALDI-TOF-MS based method for antibiotic resistance detection, MBT-ASTRA™, which is based on the comparison of growth rate of the bacteria cultivated with and without antibiotics. We demonstrate a new protocol where several parameters have been optimized and automated leading to reduced hands-on time and improved capacity to simultaneously analyse multiple clinical samples and antibiotics. Results: Ninety minutes of incubation at 37 °C with agitation was sufficient to differentiate the susceptible and resistant strains of E. coli and K. pneumoniae, for the antibiotics cefotaxime, meropenem and ciprofloxacin. In total, 841 positive blood culture analyses of 14 reference strains were performed. The overall sensitivity was 99%, specificity 99% and the accuracy 97%. The assay gave no errors for cefotaxime (n = 263) or meropenem (n = 289) for sensitive and resistant strains, whilst ciprofloxacin (n = 289) gave six (0.7%) major errors (false resistance) and four (0.5%) very major errors (false susceptibility). The intermediate strains showed a larger variety compared to the E-test MIC values. Conclusions: The hands-on time and the analysis time to detect antibiotic resistance of clinical blood samples can be substantially reduced and the sample capacity can be increased by using automation and this improved protocol.
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3. |
- Banke, Elin, et al.
(författare)
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Superantigen activates the gp130 receptor on adipocytes resulting in altered adipocyte metabolism.
- 2014
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 63:6, s. 831-840
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Tidskriftsartikel (refereegranskat)abstract
- The bacteria Staphylococcus aureus is part of the normal bacterial flora and produces a repertoire of enterotoxins which can cause food poisoning and toxic shock and might contribute to the pathogenesis of inflammatory diseases. These enterotoxins directly cross-link the T cell receptor with MHC class II, activating large amounts of T cells and are therefore called superantigens. It was recently discovered that the superantigen SEA binds to the cytokine receptor gp130. As obesity and type 2 diabetes are highly associated with inflammation of the adipose tissue and gp130 has been shown to play an important role in adipocytes, we wanted to investigate the effect of SEA on adipocyte signaling and function.
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4. |
- Berge, Andreas, et al.
(författare)
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Enterococcus faecalis bacteremia, cardiac implantable electronic device, extraction, and the risk of recurrence
- 2022
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Ingår i: Infection. - : Springer Science and Business Media LLC. - 0300-8126 .- 1439-0973. ; 50:6, s. 1517-1523
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In all patients with cardiac implantable electronic devices (CIED) and Enterococcus faecalis bacteremia (EfsB), endocarditis (IE) and CIED infection should be suspected. Guidelines recommend extraction of the CIED when CIED infection or IE is diagnosed. Whether extraction of the CIED should be done in other situations with EfsB is not known. We aimed to describe the management and outcome of patients with CIED and monomicrobial EfsB, in relation to extraction and recurrent EfsB. Methods: A population-based cohort of patients with monomicrobial EfsB from January 2014 to November 2020 was identified through microbiology registers in the Region Skåne, Sweden. Data on CIED and other clinical features were collected from medical records. Results: Among 1087 episodes of EfsB, 72 patients with CIED and monomicrobial EfsB were identified. Five of these patients were diagnosed with IE (7%), three of whom had echocardiographic changes on the CIED. Four CIED were extracted (6%). Recurrences were found in seven of 68 patients (10%) not subjected to extraction and in none of the extracted. In the group of patients without extraction, community acquisition and predisposition for IE were significantly associated with recurrent infection in univariate analyses. No infections involving the CIED were diagnosed during the recurrences. Conclusions: In patient with monomicrobial EfsB, it seems safe to omit extraction if no structural changes are found on the CIED.
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5. |
- Berge, Andreas, et al.
(författare)
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Epidemiology, bacteriology, and clinical characteristics of HACEK bacteremia and endocarditis : a population-based retrospective study
- 2020
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373.
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to describe the epidemiology, bacteriology, clinical presentation, risk factors for endocarditis (IE), diagnostic workup, and outcome of patients with bacteremia caused by the non-influenzae Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella genera (HACEK). A retrospective population-based cohort of patients with bacteremia collected from 2012 to 2017 was identified. Clinical data from identified patients were collected from medical records to classify patients, calculate incidences, analyze risk factors of IE, and describe the management and outcome of the cohort. A total of 118 episodes of HACEK bacteremia were identified, of which 27 were definite IE. The incidence of HACEK bacteremia was 5.2 and of HACEK IE 1.2 episodes per 1,000,000 inhabitants per year. Other focal infections were identified in 55 of 118 of the episodes, most commonly within the abdomen (26 episodes). The propensity to cause IE ranged from 62 in Aggregatibacter actinomycetemcomitans to 6% in Eikenella. Risk factors for IE were cardiac implantable electronical device, predisposing cardiac conditions, community acquisition, long duration of symptoms, multiple positive blood cultures, fever, heart murmur, embolization, and unknown origin of infection. The scoring system DENOVA developed to predict IE in bacteremia with Enterococcus faecalis also had a high sensitivity and specificity for predicting IE in HACEK bacteremia. The 30-day mortality was 4% in IE and 15% in non-IE bacteremia, and only one case of relapse was found. IE is common in bacteremia with Aggregatibacter, Cardiobacterium, and Kingella but relatively rare in Haemophilus and Eikenella. Treatment failures are very rare, and DENOVA can be used to evaluate the need for transesophageal echocardiography.
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6. |
- Berge, Andreas, et al.
(författare)
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Risk for Endocarditis in Bacteremia with Streptococcus-Like Bacteria : A Retrospective Population-Based Cohort Study
- 2019
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many genera and species of Streptococcus-like bacteria (SLB) can cause infective endocarditis (IE), but little is known about the epidemiology of and the risk factors for IE in SLB-bacteremia. The aim of the study was to analyze this in a cohort of patients with SLB-bacteremia, focusing on Abiotrophia, Aerococcus, Gemella, and Granulicatella. We also evaluated whether published scoring systems generated for other Gram-positive bacteria known to cause IE (HANDOC for streptococci and NOVA and DENOVA for enterococci) could be used in SLB bacteremia to decide whether transesophageal echocardiography (TEE) could be omitted. Methods: Positive blood cultures with SLB were retrieved from population-based registries in Sweden (3.2 million inhabitants), from January 2012 to December 2017. Clinical data were collected from medical records. Risk factors for IE were analyzed and the performances of the scoring systems were calculated. Results: The incidence of bacteremia with the 4 SLB genera was 30 episodes/1 000 000 population per year, of which Aerococcus contributed with 18. Among 568 episodes of bacteremia, 32 cases of IE were identified (5.6%). Infective endocarditis was most common in bacteremia with Abiotrophia (4 of 19) followed by Granulicatella (9 of 124), Gemella (6 of 87), and Aerococcus (13 of 338). NOVA had 100% sensitivity to identify IE but a low specificity (15%). For HANDOC and DENOVA, the sensitivities were 97% and 91%, respectively, whereas specificities were 85% and 90%, respectively, and numbers needed to screen were 3.6 and 2.8, respectively. Conclusions: Bacteremia with these SLB is relatively rare, and the decision whether TEE should be performed or not could be based on either HANDOC or DENOVA.
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8. |
- Bergenman, Oskar, et al.
(författare)
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Risk of infective endocarditis and complicated infection in Staphylococcus aureus bacteremia – a retrospective cohort study on the role of bacteriuria
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - 0934-9723.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: S. aureus bacteremia (SAB) is a common and severe infection with high mortality and morbidity. The clinical relevance of the finding of concurrent S. aureus bacteriuria (SABU) is debated. The goal of this study was to analyze whether a concurrent SABU is associated with complicated SAB, infective endocarditis (IE) and mortality. Methods: We conducted a retrospective cohort study, reviewing medical charts of all episodes of SAB in patients > 18 years in the region of Skåne, Sweden, between 1st of January and 31st of June 2020. Episodes where a concurrent urine culture was performed were included for analysis. An episode was considered as complicated SAB if there was either attributable mortality, recurrent infection, embolic stroke, or occurrence of a complicated focus of infection. Results: During the study period, there were 279 episodes of SAB. 154 episodes met the eligibility criteria, of whom 37 (24%) had concurrent SABU. In 78 episodes (51%), the patients had a complicated SAB. There was a significantly lower proportion of complicated SAB for episodes with concurrent SABU (32%), compared to episodes without concurrent SABU (56%), p-value 0.014. Moreover, in the cohort there were 11 episodes (7.1%) of IE and a 30 days mortality rate of 16%, with no difference between the groups with or without SABU. Conclusions: There is an association between concurrent SABU and a decreased risk for complicated SAB among patients with SAB. This study found no significant association between SABU and neither IE nor mortality for patients with SAB.
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9. |
- Bläckberg, Anna, et al.
(författare)
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Eubacterium bacteremia – a retrospective observational study of a seldom found anaerobic pathogen
- 2024
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Ingår i: Diagnostic Microbiology and Infectious Disease. - 1879-0070. ; 108:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHuman infections due to Eubacterium are rare and knowledge of the condition is limited. This study aimed to describe clinical characteristics and outcome in patients with Eubacterium bacteremia.MethodsEpisodes of Eubacterium bacteremia were identified through the clinical microbiology laboratory in Lund, Sweden. Medical records were retrospectively reviewed. Blood isolates of Eubacterium were collected and antibiotic susceptibility testing was performed with agar dilution.ResultsSeventeen patients with Eubacterium bacteremia were identified of whom six had monomicrobial bacteremia. The incidence was 1.7 cases of Eubacterium bacteremia per million inhabitants and year. The median age was 67 years (interquartile range 63-79 years), and six patients had some form of malignancy. Most of the patients an abdominal focus of infection and the 30-day mortality was low (n=1).ConclusionsInvasive infections with Eubacterium have a low incidence. The condition has a low mortality and an abdominal focus of infection, and malignancy, is common.
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10. |
- Bläckberg, Anna, et al.
(författare)
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Infective endocarditis due to Streptococcus dysgalactiae: clinical presentation and microbiological features
- 2018
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 37:12, s. 2261-2272
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of infective endocarditis (IE) caused by Streptococcus dysgalactiae (SD) is limited. This study aimed to identify the clinical and microbiological features of SD-caused IE and to investigate any possible synergy between penicillin and gentamicin on SD isolates. Cases of IE 2008-2016 due to SD reported to the Swedish Registry of Infective Endocarditis (SRIE) were identified. Isolates were emm typed and synergy between antibiotics was determined in time-kill experiments. Medical records were reviewed and SD-cases were compared to cases of IE due to other pathogens reported to the SRIE. Fifty cases of SD-caused IE were confirmed. emm types stC74a, stG62647, and stG643 were most commonly encountered. The patients had a median age of 74years (range 38-93) and were significantly older compared to patients with Staphylococcus aureus-caused IE, (65years (p=0.003)). The median time to diagnosis from symptom onset was 1day for patients with SD-caused IE which was less compared to patients with IE due to the other pathogens (2-15days). Embolization was seen in 46% and the in-hospital mortality was 8%. Etest-based methods did not indicate any synergy between penicillin and gentamicin whereas synergy was noted for four out of nine isolates applying time-kill assays. This is the largest study of SD-caused IE, a condition with an acute onset predominantly affecting elderly people. Synergy between penicillin and gentamicin against some SD isolates was distinguished but the potential benefit of this must be weighed against the risk of aminoglycoside side effects.
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