Annemieke M C Ten Bokum

Publications (6)21.32 Total impact

• Article: The case for hypervirulence through gene deletion in Mycobacterium tuberculosis.

  Annemieke M C ten Bokum, Farahnaz Movahedzadeh, Rosangela Frita, Gregory J Bancroft, Neil G Stoker
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  ABSTRACT: Deletion of genes in a pathogen is commonly associated with a reduction in its ability to cause disease. However, some rare cases have been described in the literature whereby deletion of a gene results in an increase in virulence. Recently, there have been several reports of hypervirulence resulting from gene deletion in Mycobacterium tuberculosis. Here, we explore this phenomenon in the context of the interaction between the pathogen and the host response.
  Trends in Microbiology 10/2008; 16(9):436-41. · 7.91 Impact Factor
• Source

  Available from: Johan Grooten

  Article: Cholesteroid nature of free mycolic acids from M. tuberculosis.

  Yolandy Benadie, Madrey Deysel, D Gilbert R Siko, Vanessa V Roberts, Sandra Van Wyngaardt, Simon T Thanyani, Gianna Sekanka, Annemieke M C Ten Bokum, Lynne A Collett, Johan Grooten, Mark S Baird, Jan A Verschoor
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  ABSTRACT: Mycolic acids (MAs) are a major component of the cell walls of Mycobacterium tuberculosis and related organisms. These alpha-alkyl beta-hydroxy long fatty acids have been the subject of numerous studies for their immunological properties. We previously reported that an interaction between cholesterol and mycolic acids could be responsible for the low accuracy in the serodiagnosis of TB when using free mycolic acid in an ELISA assay. The aim of this work was to investigate if this interaction could be due to a similarity in the structural properties between mycolic acids and cholesterol. The investigation revealed that patient sera cross-reacted with mycolic acids and cholesterol in an ELISA experiment suggesting that both molecules may present related functionality in a similar structural orientation. This relation was further supported by the interaction of mycolic acids with Amphotericin B (AmB), a known binding agent to ergosterol and cholesterol. Using a resonant mirror biosensor, we observed that AmB recognised both cholesterol and mycolic acids. In addition, a specific attraction was observed between mycolic acid and cholesterol by the accumulation of cholesterol from liposomes in suspension onto immobilized mycolic acids containing liposomes, detected with a biosensor technique. Combined, these results suggest that mycolic acids can assume a three-dimensional conformation similar to a sterol. This requires that mycolic acid exposes its hydroxyl group and assumes rigidity in its chain structure to generate a hydrophobic surface topology matching that of cholesterol. A particular folded conformation would be required for this, of which a few different types have already been proven to exist in monolayers of mycolic acids.
  Chemistry and Physics of Lipids 05/2008; 152(2):95-103. · 2.57 Impact Factor
• Article: Bystander macrophage apoptosis after Mycobacterium tuberculosis H37Ra infection.

  Deirdre M Kelly, Annemieke M C ten Bokum, Seonadh M O'Leary, Mary P O'Sullivan, Joseph Keane
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  ABSTRACT: Human macrophages infected with Mycobacterium tuberculosis may undergo apoptosis. Macrophage apoptosis contributes to the innate immune response against M. tuberculosis by containing and limiting the growth of mycobacteria and also by depriving the bacillus of its niche cell. Apoptosis of infected macrophages is well documented; however, bystander apoptosis of uninfected macrophages has not been described in the setting of M. tuberculosis. We observed that uninfected human macrophages underwent significant bystander apoptosis 48 and 96 h after they came into contact with macrophages infected with avirulent M. tuberculosis. The bystander apoptosis was significantly greater than the background apoptosis observed in uninfected control cells cultured for the same length of time. There was no evidence of the involvement of tumor necrosis factor alpha, Fas, tumor necrosis factor-related apoptosis-inducing ligand, transforming growth factor beta, Toll-like receptor 2, or MyD88 in contact-mediated bystander apoptosis. This newly described phenomenon may further limit the spread of M. tuberculosis by eliminating the niche cells on which the bacillus relies.
  Infection and immunity 02/2008; 76(1):351-60. · 4.21 Impact Factor
• Source

  Available from: PubMed Central

  Article: Quantification of global transcription patterns in prokaryotes using spotted microarrays.

  Ben Sidders, Mike Withers, Sharon L Kendall, Joanna Bacon, Simon J Waddell, Jason Hinds, Paul Golby, Farahnaz Movahedzadeh, Robert A Cox, Rosangela Frita, Annemieke M C Ten Bokum, Lorenz Wernisch, Neil G Stoker
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  ABSTRACT: We describe an analysis, applicable to any spotted microarray dataset produced using genomic DNA as a reference, that quantifies prokaryotic levels of mRNA on a genome-wide scale. Applying this to Mycobacterium tuberculosis, we validate the technique, show a correlation between level of expression and biological importance, define the complement of invariant genes and analyze absolute levels of expression by functional class to develop ways of understanding an organism's biology without comparison to another growth condition.
  Genome biology 02/2007; 8(12):R265. · 6.63 Impact Factor
• Article: The case for hypervirulence through gene deletion in Mycobacterium tuberculosis

  Annemieke M.C. ten Bokum, Farahnaz Movahedzadeh, Rosangela Frita, Gregory J. Bancroft, Neil G. Stoker
  [show abstract] [hide abstract]
  ABSTRACT: Deletion of genes in a pathogen is commonly associated with a reduction in its ability to cause disease. However, some rare cases have been described in the literature whereby deletion of a gene results in an increase in virulence. Recently, there have been several reports of hypervirulence resulting from gene deletion in Mycobacterium tuberculosis. Here, we explore this phenomenon in the context of the interaction between the pathogen and the host response.
  Trends in Microbiology.
• Article: Cholesteroid nature of free mycolic acids from M. tuberculosis

  Yolandy Benadie, Madrey Deysel, D. Gilbert R. Siko, Vanessa V. Roberts, Sandra Van Wyngaardt, Simon T. Thanyani, Gianna Sekanka, Annemieke M.C. Ten Bokum, Lynne A. Collett, Johan Grooten, Mark S. Baird, Jan A. Verschoor
  [show abstract] [hide abstract]
  ABSTRACT: Mycolic acids (MAs) are a major component of the cell walls of Mycobacterium tuberculosis and related organisms. These α-alkyl β-hydroxy long fatty acids have been the subject of numerous studies for their immunological properties. We previously reported that an interaction between cholesterol and mycolic acids could be responsible for the low accuracy in the serodiagnosis of TB when using free mycolic acid in an ELISA assay. The aim of this work was to investigate if this interaction could be due to a similarity in the structural properties between mycolic acids and cholesterol. The investigation revealed that patient sera cross-reacted with mycolic acids and cholesterol in an ELISA experiment suggesting that both molecules may present related functionality in a similar structural orientation. This relation was further supported by the interaction of mycolic acids with Amphotericin B (AmB), a known binding agent to ergosterol and cholesterol. Using a resonant mirror biosensor, we observed that AmB recognised both cholesterol and mycolic acids. In addition, a specific attraction was observed between mycolic acid and cholesterol by the accumulation of cholesterol from liposomes in suspension onto immobilized mycolic acids containing liposomes, detected with a biosensor technique. Combined, these results suggest that mycolic acids can assume a three-dimensional conformation similar to a sterol. This requires that mycolic acid exposes its hydroxyl group and assumes rigidity in its chain structure to generate a hydrophobic surface topology matching that of cholesterol. A particular folded conformation would be required for this, of which a few different types have already been proven to exist in monolayers of mycolic acids.
  Chemistry and Physics of Lipids.