Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations

Catherinot, Émilie; Roux, Anne-Laure; Vibet, Marie-Anne; Bellis, Gil; Ravilly, S.; Lemonnier, Lydie; Roux, E; Bernède-Bauduin, Claire; Bourgeois, M. Le; Herrmann, Jean-Louis; Guillemot, Didier; Gaillard, Jean‐Louis

doi:10.1016/j.jcf.2012.06.009

Cited by 86 publications

(94 citation statements)

References 27 publications

(45 reference statements)

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“…There is general consensus that, in CF and non-CF populations, M. abscessus is a more virulent bacteria than MAC (13,17,28,29,36), that it may be associated with a greater rate of FEV 1 decline (7,30), and that it is more difficult to treat (17,26,37). However, our results demonstrate that both MAC and M. abscessus can be cleared spontaneously in a subset of patients with CF or can result in an apparently indolent infection.…”

Section: Original Researchmentioning

confidence: 56%

“…In those who were treated, lung function decline stabilized in the year after therapy initiation even though the organism was often not eradicated. Azithromycin use has recently been shown to block autophagy, suggesting that it has the potential to predispose patients with CF to mycobacterial infection (39), although this effect has not been seen in case-control studies (29,40). In addition, a recent nested case-control study by Binder and colleagues showed that patients with CF with incident NTM infections were less likely to have had chronic azithromycin treatment in the last year (41).…”

Section: Original Researchmentioning

confidence: 99%

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Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

et al. 2014

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Rationale: Little is known about outcomes of infection with nontuberculous mycobacteria (NTM) in cystic fibrosis (CF) or about the significance of a positive NTM culture. Determining which patients are at risk for active NTM disease is clinically valuable.Objectives: To examine the clinical course of subjects with CF with an initial positive NTM culture and identify characteristics associated with active NTM disease.Methods: We performed a retrospective study of pediatric and adult subjects with CF with at least one positive NTM culture at the Colorado CF Center from 2000 to 2010.Measurements and Main Results: Mycobacterium avium complex was the first identified NTM in the majority of subjects (73%). The frequency of growing a second NTM species was 26% at 5 years. Clinical characteristics and distribution of NTM species between pediatric and adult subjects were similar except for differences in baseline FEV 1 (89% vs. 71%; P , 0.001) and coinfection with Pseudomonas aeruginosa (33% vs. 55%; P = 0.04). Over 60% of subjects had transient or persistent infection but not active NTM disease. Subjects who developed active NTM disease were distinguished from those with transient or persistent infection, respectively, by FEV 1 at the time of first positive NTM culture (72% vs. 84 or 86%; P = 0.02) and FEV 1 decline in the prior year (25.8%/yr vs. 20.7%/yr [P = 0.009] or 20.4%/yr [P = 0.001]). Conclusions:The majority of patients with CF with a first positive NTM culture do not progress to active disease. Lower lung function and accelerated lung function decline appear to be indicators of the significance of an initial positive NTM culture.

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Section: Original Researchmentioning

confidence: 56%

Section: Original Researchmentioning

confidence: 99%

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

et al. 2014

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“…Nine out of the eighteen CF patients infected with M. abscessus complex bacteria (50%) were also culture positive for Aspergillus (Table 2). Aspergillosis is associated with M. abscessus complex isolation from cystic fibrosis patients in many countries [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of Mycobacterium abscessus complex isolates in Ireland

O'Driscoll

Konjek

Heym

et al. 2016

Journal of Cystic Fibrosis

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“…DAG has been shown to activate protein kinase C, which is known to modulate the activation of neutrophils and macrophages (45). This activity further emphasizes the inflammatory response observed in CF lungs and participates in the increased virulence of M. abscessus in CF patients compared to other mycobacteria (46).…”

Section: Discussionmentioning

confidence: 83%

Mycobacterium abscessus Phospholipase C Expression Is Induced during Coculture within Amoebae and Enhances M. abscessus Virulence in Mice

et al. 2015

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Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence of M. abscessus showed that this bacterium is endowed with the metabolic pathways typically found in environmental microorganisms that come into contact with soil, plants, and aquatic environments, where free-living amoebae are frequently present. M. abscessus also contains several genes that are characteristically found only in pathogenic bacteria. One of them is MAB_0555, encoding a putative phospholipase C (PLC) that is absent from most other rapidly growing mycobacteria, including Mycobacterium chelonae and Mycobacterium smegmatis. Here, we report that purified recombinant M. abscessus PLC is highly cytotoxic to mouse macrophages, presumably due to hydrolysis of membrane phospholipids. We further showed by constructing and using an M. abscessus PLC knockout mutant that loss of PLC activity is deleterious to M. abscessus intracellular survival in amoebae. The importance of PLC is further supported by the fact that M. abscessus PLC was found to be expressed only in amoebae. Aerosol challenge of mice with M. abscessus strains that were precultured in amoebae enhanced M. abscessus lung infectivity relative to M. abscessus grown in broth culture. Our study underlines the importance of PLC for the virulence of M. abscessus. Despite the difficulties of isolating M. abscessus from environmental sources, our findings suggest that M. abscessus has evolved in close contact with environmental protozoa, which supports the argument that amoebae may contribute to the virulence of opportunistic mycobacteria.T he recognition of the role of Mycobacterium abscessus in human pathology has taken several decades, due to confusion in many studies between this mycobacterium and the very closely related species Mycobacterium chelonae. It was only in 1992 that these two species were distinguished and M. abscessus elevated to the rank of species (1).These two phylogenetically closely related, rapidly growing mycobacteria (RGM), which have identical 16S ribosomal rRNA gene sequences, are distinguished by different pathogenicity patterns. M. chelonae, generally less pathogenic than M. abscessus, is implicated in skin and soft tissue infections and only occasionally involved in lung infections. M. abscessus is currently the most frequently isolated RGM in human pathology and the main RGM involved in lung infections (2, 3), with a particular link to cystic fibrosis (CF) patients (4-6). M. abscessus is also the main RGM responsible for iatrogenic infections in humans (postinjection abscesses, cardiac surgery infections, and plastic surgery infections) (7-9).The environmental source of M. abscessus that might serve as a reservoir for human infection is currently unknown (10). Although the gene pool of M. abscessus (11) suggests that this bacterium has evolved in an aquatic environment at the interface with plant...

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Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations

Abstract: MAC affects adult patients with a mild form of CF, whereas MABSC affects younger patients with more severe CF and more frequent intravenous antimicrobial treatment.

Cited by 86 publications

References 27 publications

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

Molecular epidemiology of Mycobacterium abscessus complex isolates in Ireland

Mycobacterium abscessus Phospholipase C Expression Is Induced during Coculture within Amoebae and Enhances M. abscessus Virulence in Mice

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