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- Jönsson, Bodil, 1959, et al.
(författare)
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Molecular epidemiology of Mycobacterium abscessus, with focus on cystic fibrosis.
- 2007
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 45:5, s. 1497-504
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium abscessus has been isolated increasingly often from the respiratory tracts of cystic fibrosis (CF) patients. It is not known whether these organisms are transmitted from person to person or acquired from environmental sources. Here, colony morphology and pulsed-field gel electrophoresis (PFGE) pattern were examined for 71 isolates of M. abscessus derived from 14 CF patients, three non-CF patients with chronic respiratory M. abscessus infection or colonization, one patient with mastoiditis, and four patients with infected wounds, as well as for six isolates identified as environmental contaminants in various clinical specimens. Contaminants and wound isolates mainly exhibited smooth colony morphology, while a rough colony phenotype was significantly associated with chronic airway colonization (P=0.014). Rough strains may exhibit increased airway-colonizing capacity, the cause of which remains to be determined. Examination by PFGE of consecutive isolates from the same patient showed that they all represented a single strain, even in cases where both smooth and rough isolates were present. When PFGE patterns were compared, it was shown that 24 patients had unique strains, while four patients harbored strains indistinguishable by PFGE. Two of these were siblings with CF. The other two patients, one of whom had CF, had not had contact with each other or with the siblings. Our results show that most patients colonized by M. abscessus in the airways have unique strains, indicating that these strains derive from the environment and that patient-to-patient transmission rarely occurs.
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| 2. |
- Jönsson, Bodil, 1959
(författare)
-
Epidemiological and immunological studies of environmental mycobacteria - with focus on Mycobacterium abscessus
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mycobacterium avium, M. abscessus and M. gordonae are three mycobacterial species that are ubiquitous in the environment. M. gordonae is non-pathogenic, while M. avium and M. abscessus can cause skin abscesses and airway disease, the latter mainly in patients with cystic fibrosis. The aim of this thesis was to examine the molecular epidemiology of M. abscessus and interactions of environmental mycobacteria with the human immune system. M. abscessus isolates from the airways of cystic fibrosis patients and from skin infections in patients injured during the tsunami catastrophe in Thailand 2004 were analysed by pulsed-field gel electrophoresis (PFGE). Almost all patients had unique strains, indicating that patient-to-patient transmission was rare. M. abscessus exhibits two colony variants; smooth and rough, the latter thought to be more virulent. Rough isolates dominated in chronic airway infection, while smooth strains caused wound infection or were transient colonizers of the airways, without associated symptoms. Environmental mycobacteria induced a unique cytokine pattern in human peripheral blood mononuclear cells (PBMC) characterized by very high levels of IL-17, high levels of IL-10, moderate levels of IL-23, relatively little IFN-, and no IL-12. The cytokine pattern induced by M. abscessus, M. avium and M. gordonae was identical, despite differences in pathogenic potential. Mycobacterial surface lipids and lipoarabinomannans induced very large amounts of IL-17, but down-regulated production of Th1 cytokines. Morphological analysis of PBMC interacting with M. abscessus showed that smooth isolates were readily phagocytosed, while rough strains formed multibacterial cords that escaped phagocytosis. Instead, monocytes appeared to entrap cord-forming bacteria in meshworks containing dsDNA and histones. These meshworks resembled NETs previously described in neutrophils, but to our knowledge, extracellular traps formed by monocytes have not previously been described. Rough isolates of M. abscessus induced significantly less IL-10 and IL-23, but more IL-1 than smooth isolates. Our results suggest that cord formation increases mycobacterial virulence and that mycobacterial cell wall lipids efficiently modulate innate responses and possess unique IL-17 inducing properties. The cellular basis for this IL-17 production remains to be determined.
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