Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells

Arruda, Sérgio; Bomfim, Glória; Knights, Ronald; Huima-Byron, Tellervo; Riley, Lee W.

doi:10.1126/science.8367727

Cited by 359 publications

(268 citation statements)

References 11 publications

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“…FTT1043 encodes a macrophage infectivity potentiator protein previously found to confer virulence for several pathogens, including Legionella pneumophila 23 . We also identified a homolog of mce, involved in entry of Mycobacterium tuberculosis into host cells 24 , in the SCHU S4 genome sequence.…”

Section: Candidate Mechanisms Of Virulencementioning

confidence: 99%

The complete genome sequence of Francisella tularensis, the causative agent of tularemia

et al. 2005

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Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.

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Section: Candidate Mechanisms Of Virulencementioning

confidence: 99%

The complete genome sequence of Francisella tularensis, the causative agent of tularemia

et al. 2005

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“…Many of these proteins may interact specifically with various parts of the host defence mechanisms, i.e. uptake of mycobacteria into phagocytic and nonphagocytic cells [30], inhibition of phagosome-lysosome fusion [31,32], inhibition of presentation via MHC class I and II [19,33], induction of FAS ligand in phagocytic cells [34], inhibition of production of several cytokines [35] and possibly many more.…”

Section: Protein Secretion and Excretion And The Implications For Thementioning

confidence: 99%

Liberation of Soluble Proteins from Live and Dead Mycobacterial Cells and the Implications for Pathogenicity of Tubercle Bacilli

Wiker¹

2001

Scand J Immunol

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Soluble proteins liberated from live M. tuberculosis are translocated through the cytoplasmic membrane to à periplasmic space'. For further export of proteins across the outer permeability barrier, it is necessary to postulate an excretion mechanism possibly involving some kind of porin. Observations of the repertoire of proteins in culture filtrates after liquid culture of M. tuberculosis show that a large repertoire of various kinds of proteins cross the outer permeability barrier of tubercle bacilli indicating that the excretion mechanism has a wide range of specificities for proteins. Culture filtrates of tubercle bacilli almost always contain both truly secreted proteins and cytoplasmatically-derived proteins. It is questionable whether cytoplasmic proteins can cross an intact cytoplasmic membrane. The simplest explanation for the appearance of cytoplasmic proteins in culture filtrates of tubercle bacilli would be that they are released after disintegration of the cytoplasmic membrane in dying or dead bacilli. Tubercle bacilli armed with secreted factors that may specifically inhibit innate and adaptive immune responses, excrete these from the periplasmic space of live bacilli. Unspecific in its character, the excretion mechanism also liberates proteins that are essential for building and maintaining the cell wall, thereby reducing the effectiveness of this process. This may be part of the explanation why M. tuberculosis and other pathogenic mycobacteria grow so slowly. Finally, it may be postulated that dormant or latent tubercle bacilli use their repertoire of secreted proteins to control their intracellular habitat and that bacterial cytoplasmic proteins would not be liberated from such bacilli. The consequence would be that only immune responses to secreted proteins would be effective for elimination of the dormant stage of infection. In a situation with active infection there will be considerable growth and turnover of bacilli with liberation of all kinds of immunogenic substances from the bacilli. In this situation immunity against cytoplasmic proteins would also be effective and immunity to cytoplasmic proteins should also be effective for control of the reactivation of latent disease because as soon as the bacilli start to grow there will also be a subpopulation of dead bacilli on the arena. THE ENVELOPE OF MYCOBACTERIACompared to many other bacterial genera, the outer permeability barrier of mycobacteria is extremely tight and particularly so for M. tuberculosis [1,2]. This is owing to the unusual structure of the mycobacterial cell wall which is highly impermeable to hydrophilic solutes. Hydrophobic solutes can penetrate the barrier [1]. Antibiotics of the most hydrophobic types for example, are also the most effective drugs against mycobacteria [3,4].Considering the extreme rigidity and impermeability of the outer permeability barrier [5] of M. tuberculosis, it is a paradox that liquid cultures contain excessive amounts of soluble proteins which are much larger than the small solutes referred to...

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“…The repressed set includes members of the mce operons implicated in facilitating bacterial entry into host cells (Arruda et al, 1993;Flesselles et al, 1999). The 13-gene mce1 operon, Rv0166 to Rv0178, was downregulated.…”

Section: Mce1 Operonmentioning

confidence: 99%

The pleiotropic transcriptional response of Mycobacterium tuberculosis to vitamin C is robust and overlaps with the bacterial response to multiple intracellular stresses

et al. 2015

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Mycobacterium tuberculosis (Mtb) owes its success as a pathogen in large measure to its ability to exist in a persistent state of 'dormancy' resulting in a lifelong latent tuberculosis (TB) infection. An understanding of bacterial adaptation during dormancy will help in devising approaches to counter latent TB infection. In vitro models have provided valuable insights into bacterial adaptation; however, they have limitations because they do not disclose the bacterial response to the intracellular environment wherein the bacteria are simultaneously exposed to multiple stresses. We describe the pleiotropic response of Mtb in the vitamin C (vit C) model of dormancy developed in our laboratory. Vit C mediates a rapid regulation of genes representing~14 % of the genome in Mtb cultures. The upregulated genes were better represented in lipid, intermediary metabolism and regulatory protein categories. The downregulated genes mainly related to virulence, detoxification, information pathways and cell wall processes. A comparison of this response to that in other models indicates that vit C generates a multiple-stress environment for axenic Mtb cultures that resembles a macrophage-like environment. The bacterial response to vit C resembles responses to gaseous stresses such as hypoxia and nitric oxide, oxidative and nitrosative stresses, nutrient starvation and, notably, the activated macrophage environment itself. These responses demonstrate that the influence of vit C on Mtb gene expression extends well beyond the DevR dormancy regulon. A detailed characterization of the response to vit C is expected to disclose useful strategies to counter the adaptive mechanisms essential to Mtb dormancy.

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Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells

Cited by 359 publications

References 11 publications

The complete genome sequence of Francisella tularensis, the causative agent of tularemia

The complete genome sequence of Francisella tularensis, the causative agent of tularemia

Liberation of Soluble Proteins from Live and Dead Mycobacterial Cells and the Implications for Pathogenicity of Tubercle Bacilli

The pleiotropic transcriptional response of Mycobacterium tuberculosis to vitamin C is robust and overlaps with the bacterial response to multiple intracellular stresses

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