The many niches and strategies used by pathogenic mycobacteria for survival within host macrophages

Chastellier, Chantal de

doi:10.1016/j.imbio.2008.12.005

Cited by 99 publications

(87 citation statements)

References 105 publications

(136 reference statements)

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“…This has never been observed in bone marrow-derived mouse macrophages (BMDM) infected with either Mycobacterium avium (6), Mycobacterium bovis BCG (C. de Chastellier, unpublished data), or M. tuberculosis (C. de Chastellier, unpublished data). This may be due to species or cell type differences in lipolytic activity in M. tuberculosis-infected cells (21).…”

mentioning

confidence: 97%

Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

et al. 2014

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confidence: 97%

Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

et al. 2014

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“…The escape of M. tuberculosis has also been shown to be dependent on ESAT-6, and escaping the phagosome increases the replication rate of the bacteria (187). After the publication of this study, the ability of M. tuberculosis to escape the phagosome became a topic of controversy and it has been debated if phagosomal escape only happens in certain model systems, is an epiphenomenon generated as the bacterium exits the cells to spread to adjacent cells or simply an artifact due to experimental procedures (188)(189)(190). A recent study using a fluorescence resonance energy transfer approach taking advantage of the intrinsic beta-lactamase activity of mycobacteria have strengthened the initial observations of phagosomal escape of M. tuberculosis in human macrophages (191).…”

Section: The Fate Of the Mycobacterial Phagosomementioning

confidence: 99%

Mycobacterium tuberculosis and the human macrophage : shifting the balance through inflammasome activation

Eklund¹

2013

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Mycobacterium tuberculosis is a very successful pathogen and tuberculosis constitutes a major threat to global health worldwide. The World Health Organization (WHO) estimates that almost nine million new cases and 1.5 million deaths occur annually and the situation is worsened by increased antibiotic resistance and an extreme synergism with the HIV pandemic. M. tuberculosis primarily affects the lungs where the infection can lead to either eradication of the bacteria or the initiation of an immune response that culminates in the formation of a large cluster of immune cells termed granulomas. In these granulomas, the bacteria can either replicate and cause disease with the ultimate goal of spreading to new hosts or cause latent tuberculosis, which can persist for decades. The tools available to manage the disease are currently suboptimal and include lengthy antibiotic treatments and an inefficient vaccine resulting in poor protection. On a cellular level, M. tuberculosis primarily infects the cell designed to recognize, ingest and eradicate bacteria, namely the human macrophage. Following recognition, the macrophage phagocytoses the bacterium and tries to kill it using an array of different effector mechanisms including acidification of the bacterium-containing vacuole, different degradative enzymes and the generation of radicals. However, the bacterium is able to circumvent many of these harmful effects, leading to a tug-of-war between the bacterium and host macrophage. This thesis aims at studying the interaction between the human macrophage and M. tuberculosis to identify host factors critical for controlling growth of the bacteria. More specifically, it focuses on the role of an intracellular receptor protein called NLRP3 and its downstream effects. NLRP3 is activated in human macrophages infected by M. tuberculosis and upon activation it forms a multi-protein complex known as the inflammasome. This protein complex is known to induce the production of the proinflammatory cytokine IL-1β and specialized forms of macrophage cell death. We hypothesized that stimulating this pathway would have a beneficial effect for the host macrophage during infection with M. tuberculosis. To allow us to follow interaction between M. tuberculosis and the human macrophage, we first developed a luminometry-based method of measuring bacterial numbers and following bacterial growth over several days in infected cells. With this new assay we showed that low numbers of bacteria induced very low levels of IL-1β and failed to induce any type of cell death in the macrophage. However, when a critical number of bacteria were reached, the infected macrophages underwent necrosis, which was accompanied by high levels of IL-1β. We were also able to show that addition of vitamin D, which has been implicated as an important factor for increased killing capacity of infected macrophages, increased the production of IL-1β, which coincided with increased killing of M. tuberculosis. This effect was seen specifically in cells from patients with active...

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“…The bacilli remain in a weakly acidic and noncytolytic environment by residing in the phagosomes of phagocytes and prevent the maturation and fusion of phagosomes with lysosomes [1,2]. Establishment of an all-around close apposition between the phagosome membrane and the mycobacterial surface known as phagosome maturation block (PMB) will occur only when phagosomes contain a single mycobacterium (loner phagosomes) [3]. However, when a phagosome contains more than one mycobacterium or mycobacterial clumps (social phagosome), PMB is not achieved leading to phagosome maturation and fusion with lysosomes [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Establishment of an all-around close apposition between the phagosome membrane and the mycobacterial surface known as phagosome maturation block (PMB) will occur only when phagosomes contain a single mycobacterium (loner phagosomes) [3]. However, when a phagosome contains more than one mycobacterium or mycobacterial clumps (social phagosome), PMB is not achieved leading to phagosome maturation and fusion with lysosomes [2,3]. Thus, PMB is a strategy for altering the host immune response and there by sequestering pathogenic mycobacteria away from antigen presenting compartments [4].…”

Section: Introductionmentioning

confidence: 99%

Development of Novel Bacteriostatic Agents against Mycobacterium tuberculosis Using In silico Techniques

Anupama¹,

rangi²

2015

Pharm Anal Acta

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The cell wall of Mycobacterium tuberculosis is made up of mycolic acids which are found to play important role in pathogenesity by modification of double bonds at specific sites on mycolic acid precursors by the action of cyclopropane mycolic acid synthases (CMASs) that belong to a family of S-adenosyl-methionine-dependent methyl transferases. PcaA is an cyclopropane mycolic acid synthase required for cording, persistence and virulence of Mycobacterium tuberculosis and modifies mycolic acid by cyclopropanation of proximal double bond to cis cyclopropane generating alpha mycolic acid. A molecular docking of selected compounds was performed and the differences in their binding modes were investigated in order to design novel lead compound that can act as better antitubercular agent targeting cyclopropane mycolic acid synthases.

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The many niches and strategies used by pathogenic mycobacteria for survival within host macrophages

Cited by 99 publications

References 105 publications

Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

Mycobacterium tuberculosis and the human macrophage : shifting the balance through inflammasome activation

Development of Novel Bacteriostatic Agents against Mycobacterium tuberculosis Using In silico Techniques

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