Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice

• DOI: 10.1073/pnas.0608654104
• Publication Date: 2007-03-13T05:23:01Z
• Authors: Apoorva Bhatt; Nagatoshi Fujiwara; Kiranmai Bhatt; Sudagar S. Gurcha; Laurent Kremer; Bing Chen; John Chan; Steven A. Porcelli; Kazuo Kobayashi; Gurdyal S. Besra; William R. Jacobs
• Keywords: Mycolic acid

Mycobacterium tuberculosis, the causative agent of has two distinguishing characteristics: its ability to stain acid-fast and cause long-term latent infections in humans. Although this distinctive staining characteristic often been attributed lipid-rich cell wall, specific dye-retaining components were not known. Here we report that targeted deletion kasB, one M. tuberculosis genes encoding distinct beta-ketoacyl- acyl carrier protein synthases involved mycolic acid synthesis, results loss staining. Biochemical structural analyses revealed DeltakasB mutant strain synthesized mycolates with shorter chain lengths. An additional unexpected outcome kasB was ketomycolic trans-cyclopropanation a drastic reduction methoxymycolic trans-cyclopropanation, activities usually associated trans-cyclopropane synthase CmaA2. also markedly altered colony morphology abolished classic serpentine growth (cording), most profound effect persist infected immunocompetent mice for up 600 days without causing disease or mortality. This persistence represents model studying suggests attenuated may represent valuable vaccine candidate against tuberculosis.