Pathogenicity in the tubercle bacillus: molecular and evolutionary determinants

Gordon, Stephen V.; Bottai, Daria; Siméone, Roxane; Stinear, Timothy P.; Brosch, Roland

doi:10.1002/bies.200800191

Cited by 47 publications

(34 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The toxic CTD of CpnT challenges the paradigm that M. tuberculosis is one of the few bacterial pathogens that does not produce toxins (2). Based on our results, we propose the following model for the biological function of CpnT (Fig.…”

Section: Discussionmentioning

confidence: 80%

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Danilchanka¹,

Sun²,

Pavlenok³

et al. 2014

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

114

136

View full text Add to dashboard Cite

The ability to control the timing and mode of host cell death plays a pivotal role in microbial infections. Many bacteria use toxins to kill host cells and evade immune responses. Such toxins are unknown in Mycobacterium tuberculosis. Virulent M. tuberculosis strains induce necrotic cell death in macrophages by an obscure molecular mechanism. Here we show that the M. tuberculosis protein Rv3903c (channel protein with necrosis-inducing toxin, CpnT) consists of an N-terminal channel domain that is used for uptake of nutrients across the outer membrane and a secreted toxic C-terminal domain. Infection experiments revealed that CpnT is required for survival and cytotoxicity of M. tuberculosis in macrophages. Furthermore, we demonstrate that the C-terminal domain of CpnT causes necrotic cell death in eukaryotic cells. Thus, CpnT has a dual function in uptake of nutrients and induction of host cell death by M. tuberculosis.transport | pore | secretion

show abstract

Section: Discussionmentioning

confidence: 80%

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Danilchanka¹,

Sun²,

Pavlenok³

et al. 2014

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

114

136

View full text Add to dashboard Cite

show abstract

“…The in-depth analysis of this enormous dataset will allow specific traits linked to pathogenicity, transmissibility, and/or other strain-or strain-lineage-specific particularities to be identified that have likely been selected during mycobacterial evolution. (49). Whole-genome comparisons of M. tuberculosis with five selected mycobacterial species such as M. avium paratuberculosis (50), M. leprae (11), M. marinum (15), Mycobacterium smegmatis (GenBank accession-no.…”

Section: Mycobacterial Genomicsmentioning

confidence: 99%

“…Whole-genome comparisons of M. tuberculosis with five selected mycobacterial species such as M. avium paratuberculosis (50), M. leprae (11), M. marinum (15), Mycobacterium smegmatis (GenBank accession-no. NC_008596), and M. ulcerans (13), for example, revealed 1,072 orthologous genes that are conserved across the six species tested, thus potentially defining the minimum mycobacterial genome (15,49). Sequence comparisons of the core genes among these strains showed that M. tuberculosis is most closely related to M. marinum and least closely related to the environmental saprophyte M. smegmatis (15), which is in agreement with previous results from partial sequence analysis of the 16S rDNA (5).…”

Section: Mycobacterial Genomicsmentioning

confidence: 99%

Mycobacterial Pathogenomics and Evolution

et al. 2014

Self Cite

View full text Add to dashboard Cite

Most mycobacterial species are harmless saprophytes, often found in aquatic environments. A few species seem to have evolved from this pool of environmental mycobacteria into major human pathogens, such as Mycobacterium tuberculosis, the agent of tuberculosis, Mycobacterium leprae, the leprosy bacillus, and Mycobacterium ulcerans, the agent of Buruli ulcer. While the pathogenicity of M. ulcerans relates to the acquisition of a large plasmid encoding a polyketide-derived toxin, the molecular mechanisms by which M. leprae or M. tuberculosis have evolved to cause disease are complex and involve the interaction between the pathogen and the host.Here we focus on M. tuberculosis and closely related mycobacteria and discuss insights gained from recent genomic and functional studies. Comparison of M. tuberculosis genome data with sequences from nontuberculous mycobacteria, such as Mycobacterium marinum or Mycobacterium kansasii, provides a perception of the more distant evolution of M. tuberculosis, while the recently accomplished genome sequences of multiple tubercle bacilli with smooth colony morphology, named Mycobacterium canettii, have allowed the ancestral gene pool of tubercle bacilli to be estimated. The resulting findings are instrumental for our understanding of the pathogenomic evolution of tuberculosis-causing mycobacteria. Comparison of virulent and attenuated members of the M. tuberculosis complex has further contributed to identification of a specific secretion pathway, named ESX or Type VII secretion. The molecular machines involved are key elements for mycobacterial pathogenicity, strongly influencing the ability of M. tuberculosis to cope with the immune defense mounted by the host.

show abstract

“…Although extant strains of "M. canettii" still cause human tuberculosis, they differ significantly in infectivity and appear to be relatively ancestral [85,86]. Genomic studies indicate that the very diverse "M. canettii" isolates appear to coalesce into a form of bottleneck after which all the modern human and animal biotypes evolved in a relatively linear manner [83,84,87,88]. A plausible working hypothesis for the evolution of M. tuberculosis sensu stricto is outlined in Figure 11, highlighting the possible contribution of cell envelope lipid composition.…”

Section: Evolutionary and Pathogenicity Aspects Of Cell Envelope Compmentioning

confidence: 99%

Pathophysiological Implications of Cell Envelope Structure in Mycobacterium tuberculosis and Related Taxa

Minnikin¹,

Lee²,

Wu³

et al. 2015

Tuberculosis - Expanding Knowledge

View full text Add to dashboard Cite

Pathogenicity in the tubercle bacillus: molecular and evolutionary determinants

Cited by 47 publications

References 77 publications

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Mycobacterial Pathogenomics and Evolution

Pathophysiological Implications of Cell Envelope Structure in Mycobacterium tuberculosis and Related Taxa

Contact Info

Product

Resources

About