Disruption of the Genes Encoding Antigen 85A and Antigen 85B of
            <i>Mycobacterium tuberculosis</i>
            H37Rv: Effect on Growth in Culture and in Macrophages

Armitige, Lisa Y.; Jagannath, Chinnaswamy; Wanger, Audrey; Norris, Steven J.

doi:10.1128/iai.68.2.767-778.2000

Cited by 188 publications

(189 citation statements)

References 34 publications

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“…In an attempt to create Mtb derived vaccine strain with a potential to undergo phagosome lysosome fusion, Saikolappan et al [25] generated a double knock out (DKO) strain, by deleting the genes fbpA and sapM in Mtb (DfbpADsapM). They had previously reported that the disruption of fbpA (Ag85A) gene from Mtb resulted in the attenuation of the mutant within the macrophages [27]. Using THP1 macrophages they demonstrated that the DKO mutant showed higher attenuation as the mutant pathogen was unable to inhibit phagosome lysosome fusion in the infected host cell.…”

Section: Sapmmentioning

confidence: 99%

Bacterial Virulence Factors: Secreted for Survival

et al. 2016

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Virulence is described as an ability of an organism to infect the host and cause a disease. Virulence factors are the molecules that assist the bacterium colonize the host at the cellular level. These factors are either secretory, membrane associated or cytosolic in nature. The cytosolic factors facilitate the bacterium to undergo quick adaptive-metabolic, physiological and morphological shifts. The membrane associated virulence factors aid the bacterium in adhesion and evasion of the host cell. The secretory factors are important components of bacterial armoury which help the bacterium wade through the innate and adaptive immune response mounted within the host. In extracellular pathogens, the secretory virulence factors act synergistically to kill the host cells. In this review, we revisit the role of some of the secreted virulence factors of two human pathogens: Mycobacterium tuberculosis-an intracellular pathogen and Bacillus anthracis-an extracellular pathogen. The advances in research on the role of secretory factors of these pathogens during infection are discussed.

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Section: Sapmmentioning

confidence: 99%

Bacterial Virulence Factors: Secreted for Survival

et al. 2016

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“…Removal of TDM from the surface of M. tuberculosis results in enhanced trafficking to acidic vesicles and decreased survival of the organism within macrophages (Indrigo et al, 2002(Indrigo et al, , 2003. Relative to surface-associated TDM, organisms genetically altered to produce less TDM, or irregular TDM, exhibit reduced growth and survival both in vivo and in vitro (Armitige et al, 2000;Copenhaver et al, 2004;Glickman et al, 2000;Rao et al, 2005). Perhaps TDM's most interesting attribute is its ability to induce cytokine and chemokine production leading to granuloma formation in the lungs of responsive mice (Behling et al, 1993;Bekierkunst, 1968;Guidry et al, 2004;Lima et al, 2001;Perez et al, 2000;Yamagami et al, 2001).…”

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confidence: 99%

Mycobacterial glycolipid trehalose 6,6′-dimycolate-induced hypersensitive granulomas: contribution of CD4+ lymphocytes

2007

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The granulomatous response is a characteristic histological feature of Mycobacterium tuberculosis infection responsible for organism containment. The development of cell-mediated immunity is essential for protection against disease, as well as being required for maintenance of the sequestering granulomatous response. Trehalose 6,69-dimycolate (TDM; cord factor), a glycolipid associated with the cell wall of mycobacteria, is implicated as a key immunogenic component in M. tuberculosis infection. Models of TDM-induced hypersensitive granulomatous response have similar pathologies to that of active tuberculosis infection. Prior immunization (sensitization) of mice with TDM results in exacerbated histological damage, inflammation and lymphocytic infiltration upon subsequent TDM challenge. Adoptive transfer experiments were performed to ascertain the cell phenotype governing this response; CD4 + cells were identified as critical for development of related pathology. Mice receiving CD4 + cells from donor TDMimmunized mice demonstrated significantly increased production of Th1-type cytokines IFN-c and IL-12 within the lung upon subsequent TDM challenge. Control groups receiving naïve CD4 + cells, or CD8 + or CD19 + cells isolated from TDM-immunized donors, did not exhibit an exacerbated response. The identified CD4 + cells isolated from TDM-immunized mice produced significant amounts of IFN-c and IL-2 when exposed to TDM-pulsed macrophages in vitro. These experiments provide further evidence for involvement of a cell-mediated response in TDM-induced granuloma formation, which mimics pathological damage elicited during M. tuberculosis infection. INTRODUCTIONTuberculosis is not only a disease of the past; it is a disease of the future. More than 2 million people die each year from Mycobacterium tuberculosis infection, making it the most deadly of all infectious organisms. With nearly 2 billion people infected worldwide, tuberculosis remains a serious health threat (WHO, 2006), so continued research is needed to learn how this organism evades detection and destruction within the host.The cell wall of the M. tuberculosis bacilli is rich in lipids. They constitute more than 50 % of the dry weight of the organism and have been implicated as potential virulence factors (Kolattukudy et al., 1997). More than a half a century ago, Hubert Bloch identified cord factor as a 'toxic substance' that when extracted from virulent organisms caused them to lose their virulence (Bloch, 1950), and when added during infection exacerbated disease (Bloch & Noll, 1955). This substance was later identified as the mycobacterial glycolipid trehalose 6,69-dimycolate or TDM (Noll et al., 1956). TDM has been extensively studied over the years and many unique properties have been attributed to its presence. Removal of TDM from the surface of M. tuberculosis results in enhanced trafficking to acidic vesicles and decreased survival of the organism within macrophages (Indrigo et al., 2002(Indrigo et al., , 2003. Relative to surface-associated TDM, organi...

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“…Although individual knock-out strains for each isoform have been generated (21,22), the triple knock-out ag85ABC in M. tuberculosis has not been reported, presumably because this is lethal. Because of the apparent ability of the Ag85 enzymes to complement each other, at least as assessed by their ability to continue to grow in vitro (23,24), individual mutants have thus far failed to fully dissect the functional roles of the Ag85s in cell envelope biogenesis.…”

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confidence: 99%

The Three Mycobacterium tuberculosis Antigen 85 Isoforms Have Unique Substrates and Activities Determined by Non-active Site Regions

Backus

Dolan

Barry

et al. 2014

Journal of Biological Chemistry

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Background:The existence of three antigen 85 isoforms in Mycobacterium tuberculosis has been proposed to be due to immune evasion. Results: Mutating divergent amino acids from outside the enzyme active site changes enzyme activity and substrate preference. Conclusion: These enzymes have unique substrate preferences and are regulated by a second carbohydrate-binding site. Significance: Understanding the enzymatic function of these enzymes may provide novel chemotherapeutic strategies.

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Disruption of the Genes Encoding Antigen 85A and Antigen 85B of Mycobacterium tuberculosis H37Rv: Effect on Growth in Culture and in Macrophages

Cited by 188 publications

References 34 publications

Bacterial Virulence Factors: Secreted for Survival

Bacterial Virulence Factors: Secreted for Survival

Mycobacterial glycolipid trehalose 6,6′-dimycolate-induced hypersensitive granulomas: contribution of CD4+ lymphocytes

The Three Mycobacterium tuberculosis Antigen 85 Isoforms Have Unique Substrates and Activities Determined by Non-active Site Regions

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