The emergence of Beijing family genotypes of Mycobacterium tuberculosis and low‐level protection by bacille Calmette–Guérin (BCG) vaccines: is there a link?

Summary The world is confronted with major tuberculosis (TB) outbreaks at a time when the protection of bacillus Calmette–Guérin (BCG) vaccine has become inconsistent and controversial. Major TB outbreaks are caused by a group of genetically similar strains of Mycobacterium tuberculosis ( Mtb ) strains, including the Beijing family genotypes. The Beijing family genotypes exhibit important pathogenic features such high virulence, multi‐drug resistance and exogenous reinfection. These family strains have developed mechanisms that modulate/suppress immune responses by the host, such as inhibition of apoptosis of infected macrophages, diminished production of interleukin (IL)‐2, interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and elevated levels of IL‐10 and IL‐18. They demonstrate distinct expression of proteins, such as several species of α‐crystallin (a known Mtb virulence factor), but decreased expression of some antigens such as heat shock protein of 65 kDa, phosphate transport subunit S and a 47‐kDa protein. In addition, the Beijing family strains specifically produce a highly bioactive lipid (a polyketide synthase)‐derived phenolic glycolipid. This altered expression of proteins/glycolipids may be important factors underlying the success of the Beijing family strains. The Beijing family strains are speculated to have originated from South‐east Asia, where BCG vaccination has been used for more than 60 years. The hypothesis that mass BCG vaccination may have been a selective factor that favoured genotypic and phenotypic characteristic acquired by the Beijing family strains is discussed.