Morici and Nobuyuki Shimono, assistant professor of medicine at Kyushu University's Graduate School of Medical Sciences in Japan, are co-lead authors of the paper.
The researchers point out that even though the virulent strain of TB bacteria can be grown in a lab, it is not a likely candidate for use as a biological weapon. "Mycobacterium tuberculosis grows extremely slowly, is hard to aerosolize and, if it is not in a dormant stage, can be treated with antibiotics," said Morici, who is now a post-doctoral fellow at Tulane University's School of Medicine. "There are several other virulent organisms out there that are easier to manipulate than TB."
The researchers compared the spleens, livers and lungs of mice at various time points throughout the experiment, from 24 hours to 41 weeks after infection. They found that the progression of the unmodified TB strain hit a plateau about 17 weeks after infection, while the mce1 mutated TB strain didn't stop spreading until it killed its host.
The researchers also compared the reactions to normal and mutated forms of bacillus Calmette-Gurin (BCG), a weakened version of the TB bacteria that triggers an immune response but does not lead to disease.
They found that in the unmodified strains of both the TB bacteria and the BCG groups, there were well-defined granulomas, clusters of immune cells that surround TB bacteria to keep it in check. The researchers noticed that granulomas had not formed properly in the mutated strains of both the TB bacteria and the BCG groups.
The differences suggest that the mce1 gene mutations led to changes in the TB bacteria that impacted the host's own immune response. "It appears that the host immune system does not recognize the mutated TB organisms, so the bacteria
Contact: Sarah Yang
University of California - Berkeley