CAVITY FORMATION IN THE RABBIT MODEL OF TUBERCULOSIS

[摘要] Tuberculosis is one of the leading causes of morbidity and mortality among infectious diseases. The development of cavitary lesions is a major concern; it is believed that cavitary lesions contribute to tuberculosis disease transmission and antibiotic resistance. The progression of cavitary lesions can also be a sign of treatment failure. Despite the health significance of cavitary tuberculosis, there is currently no test or assay to assess which patients would be most likely to develop cavitary disease. Tests capable of detecting early treatment failure could be useful in clinical trial settings and save a considerable amount of money for failed drugs, as clinical trials are expensive due to long-term treatment and follow up monitoring required for tuberculosis. In this work, a non-invasive imaging tool is presented that is capable of predicting which rabbits will continue to progress to develop cavitary disease. Next a RNA sequencing study was performed to measure the global transcriptome response of the host at the cavitary lesion. One of the genes identified as being upregulated in the cavitary tissue wasmmp-1. We hypothesized that MMP-1 was involved in cavitary lesion development and tested our hypothesis by treating M. tb infected rabbits with a small molecule, RO32-3555 (Trocade), which inhibits MMP-1 activity.

[发布机构] Johns Hopkins University

[效力级别] tuberculosis

[关键词] mycobacterium;tuberculosis;CT;PET;Biology