title: Apoptosis, production of MMP9, VEGF, TNF-alpha and intracellular growth of M. tuberculosis for different genotypes and different pks5/1 genes.
abstract: BACKGROUND
  A previous study of IS6110 RFLP and spoligotyping of M. tuberculosis isolates from 152 Thai patients with tuberculous meningitis revealed a significantly higher percentage (57%) of the Beijing genotype as compared to isolates obtained from pulmonary tuberculosis. We postulated that the M. tuberculosis Beijing genotype is likely to be more virulent than others.
  
  
  OBJECTIVE
  Ten M. tuberculosis cerebrospinal fluid (CSF) isolates from five RFLP groups, together with different characteristics of pks15/1, M. tuberculosis H37Rv and M. bovis BCG, were investigated for their virulence in vitro.
  
  
  METHODS
  In this study, THP-1 cells were used as host cells to determine the intracellular growth and the induction of MMP9, VEGF, TNF-alpha and apoptosis. Determinations of the cytokine production and apoptosis were based on available commercial kits using ELISA techniques.
  
  
  RESULTS
  No significant difference in intracellular multiplication was found between the M. tuberculosis CSF isolates. Three isolates, consisting of 2 Nonthaburi and 1 heterogeneous isolate, were found to stimulate high TNF-alpha and MMP-9 production during the early infection period.They were isolated from 3 different patients, 2 of whom died with initial stages II and III. This result suggested that there might be an association between TNF-alpha and MMP-9 production that could account for the specific virulent nature of Nonthaburi strains. VEGF production was determined and comparable levels were found in all isolates. No significant apoptosis was detected in M. tuberculosis CSF isolates. No significant differences suggesting that the 2 Beijing strains are more virulent than the others were observed.
  
  
  CONCLUSIONS
  The predominance of the Beijing strains in cases of tuberculous meningitis (TBM) in Thai patients is not a result of their hypervirulence.
authors: Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10400, Thailand.
authors: Juthaporn
authors: J
authors: Yorsangsukkamol
authors: Angkana
authors: A
authors: Chaiprasert
authors: Tanapat
authors: T
authors: Palaga
authors: Therdsak
authors: T
authors: Prammananan
authors: Kiatichai
authors: K
authors: Faksri
authors: Prasit
authors: P
authors: Palittapongarnpim
authors: Narapon
authors: N
authors: Prayoonwiwat
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D005838:Genotype; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D013785:Thailand; D014376:Tuberculosis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D014774:Virulence
chemical_list: D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006867:Hydrolases; D020780:Matrix Metalloproteinase 9; C527647:HsaD protein, Mycobacterium tuberculosis