Paradoxical conservation of a set of three cellulose-targeting genes in Mycobacterium tuberculosis complex organisms

Medie, Felix Mba; Salah, Iskandar Ben; Drancourt, Michel; Henrissat, Bernard

doi:10.1099/mic.0.037812-0

Cited by 22 publications

(18 citation statements)

References 32 publications

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“…These data agree with the previous demonstration that M. tuberculosis organisms, but not M. avium organisms, were ejected from the amoeba Dictyostelium trophozoite by using an actin-based ejectosome [12]. MTC organisms may rely on their unique cellulase equipment, which are sugar cleaving enzymes capable of hydrolysing cellulose, a major component of the amoebal cyst cell wall [31], [32], to bypass amoebal cysts; the MTC organisms which still resided into the amoebal cyst, did resist glutaraldehyde, a biocide used to decontaminate medical devices, after entrapment in the amoebal cyst.…”

Section: Discussionsupporting

confidence: 92%

Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

et al. 2011

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BackgroundMost environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii.Methodology/Principal FindingsUsing optic and electron microscopy and co-culture methods, we observed that 89±0.6% of M. canettii, 12.4±0.3% of M. tuberculosis, 11.7±2% of M. bovis and 11.2±0.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P = 0.03), correlating with the significantly larger size of M. canetti organisms (P = 0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 32±2% for M. canettii, 26±1% for M. tuberculosis, 28±2% for M. bovis and 36±2% for M. avium (P = 0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P = 10−6) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P = 0.02) M. avium organisms (34×104 CFU/mL) than M. tuberculosis (42×101 CFU/mL) and M. bovis (35×101 CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde.Conclusions/SignificanceThese data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle.

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Section: Discussionsupporting

confidence: 92%

Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

et al. 2011

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“…The mechanisms and biological significance of this particular location remain to be studied. It has been established that A. polyphaga exocyst is composed of cellulose [43] and the authors have observed that mycobacteria encode one cellulose-binding protein and one or two cellulases which are indeed transcribed [44]. Cellulase encoded by mycobacteria may play a role in their unique exocyst location.…”

Section: Resultsmentioning

confidence: 99%

Surviving within the amoebal exocyst: the Mycobacterium avium complex paradigm

Salah

Drancourt

2010

BMC Microbiol

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BackgroundMost of environmental mycobacteria have been previously demonstrated to resist free-living amoeba with subsequent increased virulence and resistance to antibiotics and biocides. The Mycobacterium avium complex (MAC) comprises of environmental organisms that inhabit a wide variety of ecological niches and exhibit a significant degree of genetic variability. We herein studied the intra-ameobal location of all members of the MAC as model organisms for environmental mycobacteria.ResultsType strains for M. avium, Mycobacterium intracellulare, Mycobacterium chimaera, Mycobacterium colombiense, Mycobacterium arosiense, Mycobacterium marseillense, Mycobacterium timonense and Mycobacterium bouchedurhonense were co-cultivated with the free-living amoeba Acanthamoeba polyphaga strain Linc-AP1. Microscopic analyses demonstrated the engulfment and replication of mycobacteria into vacuoles of A. polyphaga trophozoites. Mycobacteria were further entrapped within amoebal cysts, and survived encystment as demonstrated by subculturing. Electron microscopy observations show that, three days after entrapment into A. polyphaga cysts, all MAC members typically resided within the exocyst.ConclusionsCombined with published data, these observations indicate that mycobacteria are unique among amoeba-resistant bacteria, in residing within the exocyst.

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“…38;68 Additionally, although M. tuberculosis can subsist on a variety of carbon sources and contains cellulases and other enzymes necessary for the breakdown of cellulose, no xylan degradative enzymes or modules have been found in M. tuberculosis , making LipW unlikely to be an acetyl xylan esterase. 69–71 …”

Section: Discussionmentioning

confidence: 99%

Structural Basis for the Strict Substrate Selectivity of the Mycobacterial Hydrolase LipW

et al. 2016

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The complex life cycle of Mycobacterium tuberculosis requires diverse energy mobilization and utilization strategies facilitated by a battery of lipid metabolism enzymes. Among lipid metabolism enzymes, the Lip family of mycobacterial serine hydrolases is essential to lipid scavenging, metabolic cycles, and reactivation from dormancy. Based on the homologous rescue strategy for mycobacterial drug targets, we have characterized the three-dimensional structure of full length LipW from Mycobacterium marinum, the first structure of a catalytically active Lip family member. LipW contains a deep, expansive substrate-binding pocket with only a narrow, restrictive active site, suggesting tight substrate selectivity for short, unbranched esters. Structural alignment reinforced this strict substrate selectivity of LipW, as the binding pocket of LipW aligned most closely with the bacterial acyl esterase superfamily. Detailed kinetic analysis of two different LipW homologues confirmed this strict substrate selectivity, as each homologue selected for unbranched propionyl ester substrates, irrespective of the alcohol portion of the ester. Using comprehensive substitutional analysis across the binding pocket, the strict substrate selectivity of LipW for propionyl esters was assigned to a narrow funnel in the acyl-binding pocket capped by a key hydrophobic valine residue. The polar, negatively charged alcohol-binding pocket also contributed to substrate orientation and stabilization of rotameric states in the catalytic serine. Together the structural, enzymatic, and substitutional analysis of LipW provide a connection between the structure and metabolic properties of a Lip family hydrolase that refines its biological function in active and dormant tuberculosis infection.

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Paradoxical conservation of a set of three cellulose-targeting genes in Mycobacterium tuberculosis complex organisms

Cited by 22 publications

References 32 publications

Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

Surviving within the amoebal exocyst: the Mycobacterium avium complex paradigm

Structural Basis for the Strict Substrate Selectivity of the Mycobacterial Hydrolase LipW

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