Mycobacterium tuberculosis gene expression during environmental conditions associated with latency

Voskuil, Martin I.

doi:10.1016/j.tube.2003.12.008

Cited by 65 publications

(61 citation statements)

References 16 publications

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“…Taken together, these results show that CpnT is required for survival and replication of M. tuberculosis in macrophages. Transcriptional profiling showed that cpnT expression is induced under hypoxic conditions (37) and during growth in macrophages (38), but is repressed during nonreplicating persistence (39) and in the presence of reactive oxygen and nitrogen species (40), consistent with the dual role of CpnT in survival of M. tuberculosis in macrophages and in regulating the outer membrane permeability of M. tuberculosis.…”

Section: Duf4237 Family Members (Simentioning

confidence: 69%

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Danilchanka¹,

Sun²,

Pavlenok³

et al. 2014

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

109

136

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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

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Section: Duf4237 Family Members (Simentioning

confidence: 69%

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Danilchanka¹,

Sun²,

Pavlenok³

et al. 2014

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

109

136

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“…These data build on evidence that suggest that Mtb actively modulates its lipid composition in response to the changing microenvironment. Thus, this lipidomic approach provides a working platform for the analyses of more-refi ned in vitro growth culture models that incorporate defi ned stress factors ( 19,(41)(42)(43)(44)(45)(46)(47)(48), as well as comparative analyses of lipid profi les from Mtb cells isolated from infected tissues. Such in vivo studies would provide valuable insight into the metabolism and physiology of Mtb .…”

Section: Discussionmentioning

confidence: 99%

Lipidomic analyses of Mycobacterium tuberculosis based on accurate mass measurements and the novel “Mtb LipidDB”

Sartain

Dick

Rithner

et al. 2011

Journal of Lipid Research

132

148

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pathogenesis ( 4-6 ). The abundance and biological importance of the Mtb lipids has resulted in extensive and elegant studies to elucidate their structures and functions ( 1-3 ). In many cases, the lipids of Mtb are unique to this pathogen or shared only with other members of this genus.Earlier studies demonstrate variability in lipid profi les among different strains of Mtb ( 7-11 ) and that minor variations in the structure of individual lipids can occur with changes in the growth environment (12)(13)(14)(15)(16)(17)(18)(19)(20). However, targeted and nontargeted assays that monitor changes in Mtb lipid profi les are generally performed by traditional TLC-based methods ( 21 ), and global lipidomics analyses in Mtb have been restricted due to limits in the technology to detect and rapidly identify a large number of lipids in a single experiment. Two-dimensional NMR was recently applied to examine global mycobacterial lipid profi les, and this approach allowed for the identifi cation of key lipid differences in 13 C-enriched cellular extracts ( 22 ). Although this approach easily detects changes in lipid patterns, it is limited by the complexity of the NMR spectra and the overlapping chemical properties of many lipids. Alternatively, MS-based lipidomic strategies allowing simultaneous detection, identifi cation, and quantifi cation of structurally diverse lipid components of Mtb also were evaluated. Leavell and Leary ( 23 ) developed an algorithm to analyze high-resolution Fourier transform-ion cyclotron Abstract The cellular envelope of Mycobacterium tuberculosis is highly distinctive and harbors a wealth of unique lipids possessing diverse structural and biological properties. However, the ability to conduct global analyses on the full complement of M. tuberculosis lipids has been missing from the repertoire of tools applied to the study of this important pathogen. We have established methods to detect and identify lipids from all major M. tuberculosis lipid classes through LC/MS lipid profi ling. This methodology is based on efficient chromatographic separation and automated ion identifi cation through accurate mass determination and searching of a newly created database ( Mtb LipidDB) that contains 2,512 lipid entities. We demonstrate the sensitive detection of molecules representing all known classes of M. tuberculosis lipids from a single crude extract. We also demonstrate the ability of this methodology to identify changes in lipid content in response to cellular growth phases. This work provides a customizable framework and resource to facilitate future studies on mycobacterial lipid biosynthesis and

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“…tuberculosis incubated under many of these conditions, as well as M. tuberculosis isolated from infections, has thickened cell walls, an altered morphology (86), and duplicated chromosomes and stops replicating (427,429,436,438). Persistent M. tuberculosis is thought to arrest its growth after completing chromosomal replication (437).…”

Section: What Is the State Of Dormancy Models?mentioning

confidence: 99%

“…In the case of M. tuberculosis cultured under the NRP conditions, where the culture is gently stirred in a sealed flask, resulting in a slow depletion of oxygen, the bacteria are able to resuscitate from bacteriostasis upon the addition of oxygen (438). Comparing transcription profiles from studies using the NRP model and from those using the steady-state growth in reduced oxygen model, the most striking commonality is the consistent upregulation of genes within the DosR regulon (311,428), with little else in common (427). It is likely that the DosSR system is important for an evolutionary survival response, but it is still unclear whether it is involved in latency.…”

Section: What Is the State Of Dormancy Models?mentioning

confidence: 99%

Bacterial Growth and Cell Division: a Mycobacterial Perspective

Hett

Rubín

2008

Microbiol Mol Biol Rev

332

293

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SUMMARY The genus Mycobacterium is best known for its two major pathogenic species, M. tuberculosis and M. leprae, the causative agents of two of the world's oldest diseases, tuberculosis and leprosy, respectively. M. tuberculosis kills approximately two million people each year and is thought to latently infect one-third of the world's population. One of the most remarkable features of the nonsporulating M. tuberculosis is its ability to remain dormant within an individual for decades before reactivating into active tuberculosis. Thus, control of cell division is a critical part of the disease. The mycobacterial cell wall has unique characteristics and is impermeable to a number of compounds, a feature in part responsible for inherent resistance to numerous drugs. The complexity of the cell wall represents a challenge to the organism, requiring specialized mechanisms to allow cell division to occur. Besides these mycobacterial specializations, all bacteria face some common challenges when they divide. First, they must maintain their normal architecture during and after cell division. In the case of mycobacteria, that means synthesizing the many layers of complex cell wall and maintaining their rod shape. Second, they need to coordinate synthesis and breakdown of cell wall components to maintain integrity throughout division. Finally, they need to regulate cell division in response to environmental stimuli. Here we discuss these challenges and the mechanisms that mycobacteria employ to meet them. Because these organisms are difficult to study, in many cases we extrapolate from information known for gram-negative bacteria or more closely related GC-rich gram-positive organisms.

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Mycobacterium tuberculosis gene expression during environmental conditions associated with latency

Cited by 65 publications

References 16 publications

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Lipidomic analyses of Mycobacterium tuberculosis based on accurate mass measurements and the novel “Mtb LipidDB”

Bacterial Growth and Cell Division: a Mycobacterial Perspective

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