<i>Mycobacterium abscessus</i>and Children with Cystic Fibrosis

Sermet‐Gaudelus, Isabelle; Bourgeois, M. Le; Pierre-Audigier, Catherine; Offredo, Catherine; Guillemot, Didier; Halley, Sophie; Akoua-Koffi, Chantal; Vincent, Véronique; Sivadon-Tardy, Valérie; Ferroni, Agnès; Berche, Patrick; Scheinmann, P.; Lenoir, G.; Gaillard, Jean‐Louis

doi:10.3201/eid0912.020774

Cited by 152 publications

(143 citation statements)

References 22 publications

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“…Infected macrophages migrate from the vasculature to the nervous tissues, become heavily infected (4), and eventually die (5). Apoptosis leads to the release of S variants (blue pathway) that subsequently are phagocytosed by newly recruited macrophages to form cellular aggregates (6). Bacterial multiplication is controlled, and a chronic infection is established.…”

Section: Methodsmentioning

confidence: 99%

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Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Bernut

Herrmann

Kissa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Mycobacterium abscessus is a rapidly growing Mycobacterium causing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. The M. abscessus rough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of the M. abscessus R variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears that M. abscessus is transported to the CNS within macrophages. The release of M. abscessus from apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology of M. abscessus infection and emphasizes cording as a mechanism of immune evasion.morphotype | pathogenesis | granuloma | innate immunity T he rapidly growing mycobacterium (RGM) Mycobacterium abscessus (M. abscessus) is an emerging pathogen that infects a wide spectrum of tissues in humans, including lungs, skin, and soft tissues (1, 2). M. abscessus lung disease is highly prevalent in patients with cystic fibrosis (CF) and is becoming a major issue for most CF centers worldwide (3-6). Although M. abscessus is an RGM, it can persist and cause lung disease with caseous lesions (7).M. abscessus exists as two variants: rough (R) and smooth (S). Ex vivo and in vivo studies have described the hypervirulence phenotype of the R versus the S morphotype (8, 9), and epidemiological studies have confirmed the persistence and acute respiratory syndromes caused by the R morphotype (4, 10, 11). The major difference between the R and S variants is the loss of a surface-associated glycopeptidolipid (GPL) (12). Analysis of the pathogenicity of M. abscessus has been hampered by the lack of genetic tools and the restricted panel of cellular/animal models. However, new genetic tools, including conditional gene expression, recently have been applied to both the S and R morphotypes (13, 14), but developing new animal models amenable to the manipulation of the host response is still challenging. The M. abscessus genome harbors a mercury-resistance plasmid sharing 99% identity with an episome from the slowgrowing fish pathogen Mycobacterium marinum, indicating that these species have exchanged this plasmid in a shared ecosystem (15). M. abscessus has been described in wild and captive fish species (16,17), and hand infections caused by M. abscessus have been reported in healthy fish handlers (18), sug...

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Section: Methodsmentioning

confidence: 99%

“…M. abscessus lung disease is highly prevalent in patients with cystic fibrosis (CF) and is becoming a major issue for most CF centers worldwide (3)(4)(5)(6). Although M. abscessus is an RGM, it can persist and cause lung disease with caseous lesions (7).…”

mentioning

confidence: 99%

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Bernut

Herrmann

Kissa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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302

493

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“…It is also a pulmonary pathogen in patients with cystic fibrosis (Cullen et al, 2000;Fauroux et al, 1997;Olivier et al, 2003;Sermet-Gaudelus et al, 2003). In some instances, isolation of M. abscessus from the sputum is not associated with progressive lung infection and may be the result of transient airway colonization (Griffith et al, 2007;Jönsson et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response

et al. 2011

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Mycobacterium abscessus is considered to be the most virulent of the rapidly growing mycobacteria. Generation of bacterial gene knockout mutants has been a useful tool for studying factors that contribute to virulence of pathogenic bacteria. Until recently, the optimal genetic approach to generation of M. abscessus gene knockout mutants was not clear. Based on the recent identification of genetic recombineering as the preferred approach, a M. abscessus mutant was generated in which the gene mmpL4b, critical to glycopeptidolipid synthesis, was deleted. Compared to the previously well-characterized parental strain 390S, the mmpL4B deletion mutant had lost sliding motility and the ability to form biofilm, but acquired the ability to replicate in human macrophages and stimulate macrophage Toll-like receptor 2. This study demonstrates that deletion of a gene associated with expression of a cell-wall lipid can result in acquisition of an immunostimulatory, invasive bacterial phenotype and has important implications for the study of M. abscessus pathogenesis at the cellular level.

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“…The NTM most frequently isolated from CF patients are Mycobacterium abscessus complex (MABSC) (also called Mycobacterium abscessus sensu lato, comprising the closely related species Mycobacterium asbcessus sensu stricto, Mycobacterium massiliense and Mycobacterium bolletii) and Mycobacterium avium complex. MABSC accounts for 16-51% of the species isolated [1][2][3][4][5]. In addition, MABSC fulfills the American Thoracic Society (ATS) criteria for pulmonary NTM infection in 60-80% of patients, far more than for other mycobacteria [1,6].…”

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confidence: 99%

Inhaled therapies, azithromycin andMycobacterium abscessusin cystic fibrosis patients

Catherinot¹,

Roux²,

Vibet³

et al. 2012

Eur Respir J

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Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections.We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres.No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates.In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

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Mycobacterium abscessusand Children with Cystic Fibrosis

Cited by 152 publications

References 22 publications

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response

Inhaled therapies, azithromycin andMycobacterium abscessusin cystic fibrosis patients

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