scholarly journals Differences in Rate and Variability of Intracellular Growth of a Panel of Mycobacterium tuberculosis Clinical Isolates within a Human Monocyte Model

2002 ◽  
Vol 70 (11) ◽  
pp. 6489-6493 ◽  
Author(s):  
Qing Li ◽  
Christopher C. Whalen ◽  
Jeffrey M. Albert ◽  
Rhonda Larkin ◽  
Lynn Zukowski ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Clinical Isolates ◽  
Beijing Strain ◽  
Human Monocytes ◽  
Intracellular Growth ◽  
Strain Family ◽  
Strain H37rv

ABSTRACT Significant differences were observed in the capacities of Mycobacterium tuberculosis clinical isolates to grow within human monocytes. Genotyping indicated that the four most rapidly growing isolates were members of the Beijing strain family. M. tuberculosis strain H37Rv provided more reproducible infection than the clinical isolates or M. tuberculosis Erdman.

scholarly journals CD40 Ligand (CD154) Does Not Contribute to Lymphocyte-Mediated Inhibition of Virulent Mycobacterium tuberculosis within Human Monocytes

2002 ◽  
Vol 70 (8) ◽  
pp. 4716-4720 ◽  
Author(s):  
Rhonda Larkin ◽  
Christopher D. Benjamin ◽  
Yen-Ming Hsu ◽  
Qing Li ◽  
Lynn Zukowski ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Peripheral Blood ◽  
Cd40 Ligand ◽  
Peripheral Blood Lymphocytes ◽  
Human Monocytes ◽  
Intracellular Growth ◽  
Soluble Cd40 Ligand ◽  
T Cell Lines

ABSTRACT Human monocytes displayed increased expression of CD40 following infection with virulent Mycobacterium tuberculosis. Nevertheless, soluble CD40 ligand (CD40L; also designated CD154) had no effect on the intracellular growth of the organism. Restriction of the intracellular growth of M. tuberculosis by peripheral blood lymphocytes and antigen-specific CD4+ T-cell lines likewise was not reduced by blocking anti-CD40L monoclonal antibody 5c8.

scholarly journals A Recently Evolved Sublineage of the Mycobacterium tuberculosis Beijing Strain Family Is Associated with an Increased Ability to Spread and Cause Disease

2007 ◽  
Vol 45 (5) ◽  
pp. 1483-1490 ◽  
Author(s):  
M. Hanekom ◽  
G. D. van der Spuy ◽  
E. Streicher ◽  
S. L. Ndabambi ◽  
C. R. E. McEvoy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Beijing Strain ◽  
Strain Family

scholarly journals Different Transcriptional Profiles of Human Monocyte-Derived Dendritic Cells Infected with Distinct Strains ofMycobacterium tuberculosisandMycobacterium bovisBacillus Calmette-Guérin

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Nunzia Sanarico ◽  
Alessia Colone ◽  
Manuela Grassi ◽  
Viviana Speranza ◽  
Daniela Giovannini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Expression Profiles ◽  
Laboratory Strain ◽  
Human Monocyte ◽  
Bacillus Calmette Guerin ◽  
Intracellular Growth ◽  
Strain Dependent

In order to analyze dendritic cells (DCs) activation following infection with different mycobacterial strains, we studied the expression profiles of 165 genes of human monocyte-derived DCs infected with H37Rv, a virulentMycobacterium tuberculosis(MTB) laboratory strain, CMT97, a clinical MTB isolate,Mycobacterium bovisbacillus Calmette-Guérin (BCG), Aventis Pasteur, and BCG Japan, both employed as vaccine against tuberculosis. The analysis of the gene expression reveals that, despite a set of genes similarly modulated, DCs response resulted strain dependent. In particular, H37Rv significantly upregulated EBI3 expression compared with BCG Japan, while it was the only strain that failed to release a significant IL-10 amount. Of note, BCG Japan showed a marked increase in CCR7 and TNF-αexpression regarding both MTB strains and it resulted the only strain failing in exponential intracellular growth. Our results suggest that DCs display the ability to elicit a tailored strain-specific immune response.

scholarly journals Comparison of Mycobacterium tuberculosis Genomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

Yeast ◽  
2000 ◽  
Vol 1 (4) ◽  
pp. 272-282
Author(s):  
Timothy B. L. Ho ◽  
Brian D. Robertson ◽  
G. Michael Taylor ◽  
Rory J. Shaw ◽  
Douglas B. Young
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hot Spots ◽  
High Frequency ◽  
Biological Diversity ◽  
Variable Region ◽  
Clinical Isolates ◽  
Insertion Element ◽  
Genomic Deletions ◽  
Nucleotide Repeats ◽  
Strain H37rv

The Mycobacterium tuberculosis complex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity in M. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of the M. tuberculosis-specific IS6110 insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110 element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110 elements as the most likely mechanism of the deletion events. IS6110 insertion into hot-spots within the genome of M. tuberculosis provides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.

scholarly journals Molecular Characterization of Clinical Isolates of Mycobacterium tuberculosis and Their Association with Phenotypic Virulence in Human Macrophages

2007 ◽  
Vol 14 (10) ◽  
pp. 1279-1284 ◽  
Author(s):  
K. C. Wong ◽  
W. M. Leong ◽  
H. K. W. Law ◽  
K. F. Ip ◽  
J. T. H. Lam ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Virulent Strain ◽  
Bacterial Load ◽  
Clinical Isolates ◽  
Avirulent Strain ◽  
Activated Macrophages ◽  
Beijing Family ◽  
Intracellular Growth

ABSTRACT Among 125 clinical isolates of Mycobacterium tuberculosis collected in Hong Kong and Shanghai, China, between 2002 and 2004, IS6110 typing revealed that 71 strains (57%) belonged to the Beijing family. The intracellular growth of the strains in human peripheral blood monocyte-derived macrophages was measured ex vivo on days 0, 3, 6, and 10. Among all tested strains, three hypervirulent strains showed significant increases in intracellular growth after 10 days of incubation. With an initial bacterial load of 104 CFU, most of the clinical isolates and H37Ra (an avirulent strain) exhibited no intracellular survival on day 10, while the three hypervirulent strains together with H37Rv (a virulent strain) showed on average a two- to fourfold rise in CFU count. These three hypervirulent strains belonging to a non-Beijing family were isolated from patients suffering from tuberculosis meningitis. Cytokines secreted by gamma interferon-activated macrophages were measured daily after challenge with selected strains of M. tuberculosis. The levels of tumor necrosis factor alpha were elevated after 24 h of infection among all strains, but the levels were significantly lower among the three hypervirulent strains, whereas interleukin 10 (IL-10) and IL-12 were not detected. Results were concordant with the differential expression of the corresponding cytokine genes in activated macrophages, as monitored by real-time PCR. Our findings highlighted that these three hypervirulent strains may possess an innate mechanism for escaping host immunity, which accounts for their characteristic virulence in patients presenting with a more severe form of disease.

scholarly journals Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanida Laopanupong ◽  
Pinidphon Prombutara ◽  
Phongthon Kanjanasirirat ◽  
Salisa Benjaskulluecha ◽  
Atsadang Boonmee ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Reference Strain ◽  
Beijing Genotype ◽  
Cell Periphery ◽  
Beijing Strain ◽  
Perinuclear Region ◽  
Rna Seq ◽  
Autophagy Induction ◽  
Infected Cells ◽  
Strain H37rv

AbstractInduction of host cell autophagy by starvation was shown to enhance lysosomal delivery to mycobacterial phagosomes, resulting in the restriction of Mycobacterium tuberculosis reference strain H37Rv. Our previous study showed that strains belonging to M. tuberculosis Beijing genotype resisted starvation-induced autophagic elimination but the factors involved remained unclear. Here, we conducted RNA-Seq of macrophages infected with the autophagy-resistant Beijing strain (BJN) compared to macrophages infected with H37Rv upon autophagy induction by starvation. Results identified several genes uniquely upregulated in BJN-infected macrophages but not in H37Rv-infected cells, including those encoding Kxd1 and Plekhm2, which function in lysosome positioning towards the cell periphery. Unlike H37Rv, BJN suppressed enhanced lysosome positioning towards the perinuclear region and lysosomal delivery to its phagosome upon autophagy induction by starvation, while depletion of Kxd1 and Plekhm2 reverted such effects, resulting in restriction of BJN intracellular survival upon autophagy induction by starvation. Taken together, these data indicated that Kxd1 and Plekhm2 are important for the BJN strain to suppress lysosome positioning towards the perinuclear region and lysosomal delivery into its phagosome during autophagy induction by starvation to evade starvation-induced autophagic restriction.

scholarly journals Mycobacterium tuberculosis Catalase and Peroxidase Activities and Resistance to Oxidative Killing in Human Monocytes In Vitro

1999 ◽  
Vol 67 (1) ◽  
pp. 74-79 ◽  
Author(s):  
Claudia Manca ◽  
Simon Paul ◽  
Clifton E. Barry ◽  
Victoria H. Freedman ◽  
Gilla Kaplan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Catalase Activity ◽  
Laboratory Strain ◽  
Activity Levels ◽  
Human Monocytes ◽  
Alkyl Hydroperoxide ◽  
Oxidative Metabolites ◽  
Catalase Peroxidase ◽  
Strain H37rv

ABSTRACT Mycobacterium tuberculosis has a relatively high resistance to killing by hydrogen peroxide and organic peroxides. Resistance may be mediated by mycobacterial catalase-peroxidase (KatG) and possibly by alkyl hydroperoxide reductase (AhpC). To determine the interrelationship between sensitivity to H2O2, catalase and peroxidase activities, and bacillary growth rates measured both intracellularly in human monocytes and in culture medium, we examined one laboratory strain, two clinical isolates, and three recombinant strains of M. tuberculosis with differing levels of KatG and AhpC. Five of the mycobacterial strains had intracellular doubling times of 27 to 32 h, while one KatG-deficient clinical isolate (ATCC 35825) doubled in ∼76 h. Killing of mycobacteria by exogenously added H2O2 was more pronounced for intracellular bacilli than for those bacilli derived from disrupted monocytes. Strains with no detectable KatG expression or catalase activity were relatively sensitive to killing (43 to 67% killing) by exogenous H2O2. However, once even minimal catalase activity was present, mycobacterial catalase activity over a 10-fold range (0.56 to 6.2 U/mg) was associated with survival of 85% of the bacilli. Peroxidase activity levels correlated significantly with resistance of the mycobacterial strains to H2O2-mediated killing. An endogenous oxidative burst induction by 4β-phorbol 12β-myristate 13α-acetate treatment of infected monocytes reduced the viability of the KatG null strain (H37Rv Inhr) but not the KatG-overexpressing strain [H37Rv(pMH59)]. These results suggest that mycobacterial resistance to oxidative metabolites (including H2O2 and other peroxides) may be an important mechanism of bacillary survival within the host phagocyte.

scholarly journals Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth

Microbiology ◽  
2009 ◽  
Vol 155 (4) ◽  
pp. 1272-1281 ◽  
Author(s):  
Shiping Wu ◽  
Peter F. Barnes ◽  
Buka Samten ◽  
Xiuhua Pang ◽  
Sébastien Rodrigue ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Isolate ◽  
Expression Patterns ◽  
Laboratory Strain ◽  
Human Monocyte ◽  
Broth Culture ◽  
Multicopy Plasmid ◽  
Intracellular Growth ◽  
Elevated Expression ◽  
Monocyte Cell

There is growing evidence that strains of Mycobacterium tuberculosis differ in pathogenicity and transmissibility, but little is understood about the contributory factors. We have previously shown that increased expression of the principal sigma factor, SigA, mediates the capacity of M. tuberculosis strain 210 to grow more rapidly in human monocytes, compared with other strains. Strain 210 is part of the widespread W-Beijing family of M. tuberculosis strains and includes clinical isolate TB294. To identify genes that respond to changes in SigA levels and that might enhance intracellular growth, we examined RNA and protein expression patterns in TB294-pSigA, a recombinant strain of TB294 that overexpresses sigA from a multicopy plasmid. Lysates from broth-grown cultures of TB294-pSigA contained high levels of Eis, a protein known to modulate host–pathogen interactions. DNA microarray analysis indicated that the eis gene, Rv2416c, was expressed at levels in TB294-pSigA 40-fold higher than in the vector control strain TB294-pCV, during growth in the human monocyte cell line MonoMac6. Other genes with elevated expression in TB294-pSigA showed much smaller changes from TB294-pCV, and the majority of genes with expression differences between the two strains had reduced expression in TB294-pSigA, including an unexpected number of genes associated with the DNA-damage response. Real-time PCR analyses confirmed that eis was expressed at very high levels in TB294-pSigA in monocytes as well as in broth culture, and further revealed that, like sigA, eis was also more highly expressed in wild-type TB294 than in the laboratory strain H37Rv, during growth in monocytes. These findings suggested an association between increased SigA levels and eis activation, and results of chromatin immunoprecipitation confirmed that SigA binds the eis promoter in live TB294 cells. Deletion of eis reduced growth of TB294 in monocytes, and complementation of eis reversed this effect. We conclude that SigA regulates eis, that there is a direct correlation between upregulation of SigA and high expression levels of eis, and that eis contributes to the enhanced capacity of a clinical isolate of M. tuberculosis strain 210 to grow in monocytes.

scholarly journals Mycobacterium tuberculosis Beijing outbreak in a school in Marseille, France, 2012

2013 ◽  
Vol 18 (2) ◽  
Author(s):  
F Golesi ◽  
J Brignatz ◽  
M Bellenfant ◽  
D Raoult ◽  
M Drancourt
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Technical College ◽  
School Setting ◽  
Sequence Type ◽  
Beijing Strain ◽  
Strain Family

Between January and September 2012, a teacher and four students at a technical college in Marseille, France, developed pulmonary tuberculosis. All Mycobacterium tuberculosis isolates from these cases were identical and belonged to the Beijing strain family, multispacer sequence type 72, a rare genotype identified only once in our laboratory in the previous two years. This report highlights once more the potential for M. tuberculosis Beijing strains to cause outbreaks, this time in a school setting.

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