title: Heterogeneity of phenotypic characteristics of the modern and ancestral Beijing strains of Mycobacterium tuberculosis.
abstract: BACKGROUND
  The Beijing strain of Mycobacterium tuberculosis (MTB) is of great concern because this hypervirulent strain has caused numerous tuberculosis outbreaks. However, the mechanisms that allow the MTB Beijing strain to be highly pathogenic remain unclear and previous studies have revealed heterogeneity within this family.
  
  
  OBJECTIVE
  To determine the association between some phenotypic characteristics and phylogroups of the Beijing strain of MTB.
  
  
  METHODS
  Eight Beijing strains, 5 modern and 3 ancestral sublineages, were selected from the phylogroups of MTB. The selection was based on copy number of IS6110 at NTF, region of differences, and single nucleotide polymorphisms. The abilities of these strains to grow intracellularly in THP-1 macrophages, to induce apoptosis, necrosis, and cytokines production were examined using quantitative real-time PCR and commercially available ELISA kits, respectively.
  
  
  RESULTS
  There were some significant differences between the two sublineages of the Beijing strain of MTB. The ancestral Beijing sublineages showed higher intracellular growth rates (p < 0.05) and necrosis induction rates (p < 0.01) than the modern Beijing sublineages. By contrast, the modern Beijing sublineages induced lower apoptosis and protective cytokine responses, i.e., TNF-α (p < 0.05) and IL-6 (p < 0.01) and higher non-protective IL-10 response. The modern Beijing sublineages may have evolved so that they have greater ability to diminish host defense mechanisms. The slower growth rate and reduced necrosis induction in host cells might allow the bacteria to cause a persistent infection.
  
  
  CONCLUSIONS
  The results revealed a phylogroup-associated heterogeneity of phenotypes among MTB Beijing sublineages.
authors.affiliation: Department of Microbiology, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand.
authors.forename: Kiatichai
authors.initials: K
authors.lastname: Faksri
authors.forename: Angkana
authors.initials: A
authors.lastname: Chaiprasert
authors.forename: Clarie
authors.initials: C
authors.lastname: Pardieu
authors.forename: Nicola
authors.initials: N
authors.lastname: Casali
authors.forename: Tanapat
authors.initials: T
authors.lastname: Palaga
authors.forename: Therdsak
authors.initials: T
authors.lastname: Prammananan
authors.forename: Prasit
authors.initials: P
authors.lastname: Palittapongarnpim
authors.forename: Naraporn
authors.initials: N
authors.lastname: Prayoonwiwat
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
mesh_terms: D045744:Cell Line, Tumor; D002681:China; D016207:Cytokines / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D014376:Tuberculosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016207:Cytokines