Differences in genetic mutations in BCG strains isolated from brain and lung tissue of a patient infected with Mycobacterium bovis, after receiving the Bacillus Calmette-Guérin vaccine

Authors

• H Tettelin
• CB Korol
• SJ Shallom
• AF Freeman
• E Sampaio
• SM Holland
• SD Rosenzweig
• AM Zelazny

Abstract

M. tuberculosis is an intracellular pathogen that causes tuberculosis and is responsible for more human deaths than any other pathogen. A live attenuated bacillus Calmette-Guérin (BCG) vaccine is used in the control of tuberculosis. The attenuated bacillus Calmette-Guérin (BCG) is a derivative of Mycobacterium bovis, a virulent tubercle bacillus which is closely related to M. tuberculosis. Original studies using subtractive genomic hybridization have identified 3 distinct genomic regions (RD1, RD2 and RD3) between a BCG strain, M. bovis and M. tuberculosis. The BCG vaccine has been used for a long time and different countries use different types of BCG sub-strains which may have variations and hence result in differing efficacy with some studies showing that the BCG vaccine could have adverse reactions in some instances. The current study is a first reported case of disseminated BCG disease in a patient given the BCG vaccine. Whole genome sequence analysis was done to compare genomic differences in the original BCG vaccine strain (vacuna BCG SSI 0702010) given to the patient as part of the vaccine and the the mutations in the M. bovis isolate obtained from the brain and lung tissue from this patient. Here we highlight genes involved in the lipid and fatty acid metabolism, cell wall proteins and proteins involved in bacterial secretion systems. The majority of the mutations identified were located in genes involved in lipid and fatty acid metabolism. SNP Mutations between the brain and lung tissues were mostly similar with a few exceptions that were unique.

Scientific Focus Area: Computational Biology

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