Spectrum of CNS disease caused by rapidly growing mycobacteria

Talati, Naasha J; Rouphael, Nadine; Kuppalli, Krutika; Franco‐Paredes, Carlos

doi:10.1016/s1473-3099(08)70127-0

Cited by 62 publications

(57 citation statements)

References 58 publications

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“…Abscesses in the CNS developed rapidly and were followed by larval death. This observation is of particular interest in light of recent clinical reports of human patients with M. abscessus infections in the CNS (39,40). Interestingly, in ZF embryos the colonization of the CNS by infected macrophages coincides with the appearance of the microglia, the resident brain macrophages (41).…”

Section: Discussionmentioning

confidence: 82%

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Bernut

Herrmann

Kissa

et al. 2014

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

297

493

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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: Discussionmentioning

confidence: 82%

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Bernut

Herrmann

Kissa

et al. 2014

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

297

493

View full text Add to dashboard Cite

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“…M. abscessus is also regarded as a major rapidly-growing mycobacterial species responsible for nosocomial and iatrogenic infections in humans. Moreover, several recent reports highlighted the possibility that M. abscessus could cross the blood-brain barrier and induce important lesions in the central nervous system (CNS) 5,6 . Despite being a rapid grower, M. abscessus exhibits also several pathogenic features that are related to those of Mycobacterium tuberculosis, including the capacity to remain silent for years within granulomatous structures and to generate caseous lesions in the lungs 7 .…”

Section: Introductionmentioning

confidence: 99%

Deciphering and Imaging Pathogenesis and Cording of <em>Mycobacterium abscessus</em> in Zebrafish Embryos

Bernut

Dupont

Sahuquet

et al. 2015

JoVE

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Zebrafish (Danio rerio) embryos are increasingly used as an infection model to study the function of the vertebrate innate immune system in host-pathogen interactions. The ease of obtaining large numbers of embryos, their accessibility due to external development, their optical transparency as well as the availability of a wide panoply of genetic/immunological tools and transgenic reporter line collections, contribute to the versatility of this model. In this respect, the present manuscript describes the use of zebrafish as an in vivo model system to investigate the chronology of Mycobacterium abscessus infection. This human pathogen can exist either as smooth (S) or rough (R) variants, depending on cell wall composition, and their respective virulence can be imaged and compared in zebrafish embryos and larvae. Micro-injection of either S or R fluorescent variants directly in the blood circulation via the caudal vein, leads to chronic or acute/lethal infections, respectively. This biological system allows high resolution visualization and analysis of the role of mycobacterial cording in promoting abscess formation. In addition, the use of fluorescent bacteria along with transgenic zebrafish lines harbouring fluorescent macrophages produces a unique opportunity for multi-color imaging of the host-pathogen interactions. This article describes detailed protocols for the preparation of homogenous M. abscessus inoculum and for intravenous injection of zebrafish embryos for subsequent fluorescence imaging of the interaction with macrophages. These techniques open the avenue to future investigations involving mutants defective in cord formation and are dedicated to understand how this impacts on M. abscessus pathogenicity in a whole vertebrate. Video LinkThe video component of this article can be found at

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“…Group IV NTM, according to Runyon's original classification, 9 such as Mycobacterium fortuitum, M. chelonae, and M. abscessus, are distinguished as rapidly growing mycobacteria (RGM) and can be isolated during the 1st week of incubation. They are variably acid-fast positive and are sometimes reported as branching grampositive rods, 10 which may confuse the clinical picture and delay appropriate therapy.…”

confidence: 99%

“…They have been isolated in 55% of water supplies to dialysis centers and 30%-78% of soil specimens 10 and are commonly found in tap water. Different NTM species have the propensity to cause infection in specific clinical settings.…”

Section: Epidemiologymentioning

confidence: 99%

“…The most comprehensive review of CNS disease 10 caused by rapidly growing mycobacteria includes 19 reported cases since 1970, not including single cases of intrathecal baclofen pump infection, 1 a Mycobacterium goodii shunt infection, 11 or our case. Of the 19 primary and secondary CNS infections reviewed, 14 were caused by M. fortuitum.…”

Section: Cns Infection With Rapidly Growing Mycobacteriamentioning

confidence: 99%

See 1 more Smart Citation

Ventriculoperitoneal shunt infection with Mycobacterium fortuitum: a rare offending organism

Cadena¹,

Wiedeman

Boggan³

2014

PED

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Postsurgical infection is one of the greatest potential morbidities of ventriculoperitoneal shunt surgery. The majority of infections can be linked to contamination with skin flora at the time of surgery, a phenomenon that has been well described. However, there is a paucity of literature regarding infection with nontuberculous mycobacteria. The authors report a case of postoperative ventriculoperitoneal shunt infection with Mycobacterium fortuitum and review the available neurosurgical literature and treatment strategies.

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Spectrum of CNS disease caused by rapidly growing mycobacteria

Cited by 62 publications

References 58 publications

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Deciphering and Imaging Pathogenesis and Cording of <em>Mycobacterium abscessus</em> in Zebrafish Embryos

Ventriculoperitoneal shunt infection with Mycobacterium fortuitum: a rare offending organism

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