Johne's disease is a chronic diarrhea affecting all ruminants. Mycobacterium avium subsp. paratuberculosis (MAP), a slowly growing mycobacteria, is the etiologic agent. There is also a concern that MAP might be a causative agent of some cases of inflammatory bowel disease in humans, especially Crohn's disease. Food products including pasteurized bovine milk have been suggested as potential sources of human infection. This review addresses microbial factors that may contribute to its pathogenicity. In addition, the experimental evidence defining MAP as the cause of Johne's disease and the issues and controversies surrounding its potential pathogenic role in humans are discussed.
Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome. Mycobacterium tuberculosis is a pathogen associated with the deaths of millions of people worldwide annually. Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. The present study describes a system using Mycobacterium smegmatis, an avirulent mycobacterium, to deliver the lytic phage TM4 where both M. avium and M. tuberculosis reside within macrophages. These results showed that treatment of M. avium-infected, as well as M. tuberculosis-infected, RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4, resulted in a significant time- and titer-dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fuses with the M. avium vacuole in macrophages. These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.
D-cycloserine (DCS) is only used with multi-drug resistant strains of tuberculosis because of serious side-effects. DCS is known to inhibit cell wall biosynthesis, but the in vivo lethal target is still unknown. We have applied NMR-based metabolomics combined with principal component analysis to monitor the in vivo affect of DCS on M. smegmatis. Our analysis suggests DCS functions by inhibiting multiple protein targets.
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