| 1. |
- Hoffner, S, et al.
(författare)
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Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience
- 2013
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 17:11, s. 1486-1490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organizations yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. less thanbrgreater than less thanbrgreater thanOBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. less thanbrgreater than less thanbrgreater thanMETHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. less thanbrgreater than less thanbrgreater thanRESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.
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| 2. |
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| 3. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Non-tuberculous mycobacteria and their surface lipids efficiently induced IL-17 production in human T cells
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:13, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-17 (IL-17) is produced by a subset of CD4(+) T helper (Th) lymphocytes known as Th17 cells. In humans, IL-1 beta, enhanced by IL-6 and IL-23 is crucial for differentiation of these cells. IL-17 evokes inflammation and is involved in host defence against microorganisms, although little is known about its role in diseases caused by non-tuberculous mycobacteria. The genus Mycobacterium contains both obligate and opportunistic pathogens as well as saprophytes, and the mycobacterial cell envelope is unique in its abundance of lipids. Here we investigated IL-17 and IL-23 production in human PBMC in response to intact UV-inactivated mycobacteria and mycobacterial surface lipids from two opportunistic (Mycobacterium avium and Mycobacterium abscessus) and one generally non-pathogenic (Mycobacterium gordonae) species. Representative Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria were included as controls. Intact mycobacteria induced production of large amounts of IL-17, while IL-17 responses to control bacteria were negligible. Purified CD4(+) T cells, but not CD4-depleted cell fractions, produced this IL-17. Isolated mycobacterial surface lipids induced IL-17, but not IL-23 production. The ability of the non-tuberculous mycobacteria to induce IL-17 production in CD4(+) T cells was the same regardless of the pathogenic potential of the particular mycobacterial species.
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| 4. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Phagocytosis and cytokine response to rough and smooth colony variants of Mycobacterium abscessus by human peripheral blood mononuclear cells.
- 2013
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 121:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium abscessus is a non-tuberculous mycobacteria able to cause opportunistic infections in selected patient groups. During the last decades it has emerged as a cause of chronic pulmonary infection in patients with cystic fibrosis (CF). M. abscessus strains exhibit either smooth or rough colony morphology. Strains exhibiting the rough phenotype more often cause pulmonary infections in CF patients than did the smooth ones. Here, we examined phagocytosis and production of cytokines by human peripheral blood mononuclear cells, in response to M. abscessus strains with smooth and rough colony phenotype. The rough isolates all formed multicellular cords, similar to what is observed in Mycobacterium tuberculosis. Monocytes were generally unable to internalize these rough cord isolates, in contrast with the smooth ones. Furthermore, the rough M. abscessus strains induced a distinct cytokine profile differing from that induced by the smooth ones. Rough isolates induced significantly less IL-10 and tumour necrosis factor compared to smooth strains, but more IL-1β. Both varieties induced equal amounts of IFN-γ, IL-17, IL-23, IL-6, IL-8 and equally little IL-12. The ability to withstand phagocytosis might be a virulence factor contributing to the capacity of rough M. abscessus strains to give persistent pulmonary infections.
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| 5. |
- Jönsson, Bodil, 1959, et al.
(författare)
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The surface lipids of non-tuberculous mycobacteria suppress production of phagocyte activating cytokines in human peripheral blood mononuclear cells
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:9, s. 768-777
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Tidskriftsartikel (refereegranskat)abstract
- The genus Mycobacterium includes obligate pathogens as well as opportunistic and non-pathogenic species ubiquitous in the environment. Mycobacteria have a unique cell wall abundant in lipids. Here we investigated cytokine production by human peripheral blood mononuclear cells (PBMC) in response to the opportunistic mycobacteria Mycobacterium avium and Mycobacterium abscessus, the non-pathogenic Mycobacterium gordonae and extracted surface lipids from the three species. The cytokine response elicited by mycobacteria, regardless of their pathogenic potential, differed distinctly from that induced by control Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria. Mycobacteria induced no IL-12 and less TNF and IFN-γ compared with conventional Gram-positive bacteria. IL-10 was induced by all the mycobacteria and this production was partly responsible for the down-regulation of IL-12 and IFN-γ. The capacity of the Gram-positive bacterium E. faecalis to induce IL-12, as well as TNF and IFN-γ, in human PBMCs was strongly reduced when mycobacterial lipids were added. The mycobacterial surface lipids down-regulated the production of IL-12 and IFN-γ without eliciting IL-10 production. Our results show that mycobacteria evade triggering production of phagocyte activating cytokines (IL-12, TNF and IFN-γ) and that the mycobacterial cell wall surface lipids may play a significant role in this process.
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| 6. |
- Kondori, Nahid, 1967, et al.
(författare)
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High recovery rate of Exophiala dermatitidis in the airways of cystic fibrosis patients is associated with pancreatic insufficiency.
- 2011
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Ingår i: Journal of clinical microbiology. - 1098-660X. ; Mar (49):3, s. 1004-9
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Tidskriftsartikel (refereegranskat)abstract
- The black pigmented fungus, Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens of CF patients, transplant recipients and subjects with other respiratory disorders in Sweden. Secondly, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways, and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples (n=492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens of 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6-25 days of incubation on erythritol-chloramphenicol (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples (P= 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis. To conclude, E. dermatitidis is a frequent colonizer of the respiratory tract of CF patients in Sweden, and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic or not remains to be elucidated.
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| 7. |
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| 8. |
- Winther, Malene, et al.
(författare)
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Antibacterial activity of pepducins, allosterical modulators of formyl Peptide receptor signaling.
- 2014
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Ingår i: Antimicrobial agents and chemotherapy. - 1098-6596. ; 58:5, s. 2985-8
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Tidskriftsartikel (refereegranskat)abstract
- Pepducins containing a fatty acid linked to an amino acid sequence derived from cytosolic parts of a G-protein-coupled receptor (GPCR) constitute a new group of lipopeptide tools in GPCR studies. Pepducins corresponding to the third intracellular loop of formyl peptide receptor 2 (FPR2) activate human neutrophils, and we show here that, in addition, these allosteric modulators of receptor activity also kill bacteria. The functional dualism of FPR2 pepducins could potentially be explored as a novel class of antibacterial drugs with immunomodulatory properties.
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