The emergence of Beijing family genotypes of Mycobacterium tuberculosis and low-level protection by bacille Calmette-Guérin (BCG) vaccines: is there a link?
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)-gamma, tumour necrosis factor (TNF)-alpha and elevated levels of IL-10 and IL-18. They demonstrate distinct expression of proteins, such as several species of alpha-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.
Abebe
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University of Oslo, International Community Health, Oslo, Norway. f.a.worke@medisin.uio.no
Bjune
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D001500:BCG Vaccine; D015373:Bacterial Typing Techniques; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014774:Virulence
D001500:BCG Vaccine