Mycobacteria relevance

Treatment problems that can arise are mainly of two types adverse reactions (collateral, toxic, or hypersusceptibility reactions), and initial or acquired resistance of Mycobacterium tuberculosis, Mycobacterium bovis, or non-tuberculous mycobacteria to one or more of the antituberculosis drugs. The latter probably only occurs when the patient has not taken the full combination or the full doses of the drugs all the time. Combination formulations are thus particularly useful. Multidrug-resistant tuberculosis, defined as resistance against at least isoniazid and rifampicin, is the most clinically relevant form of resistance to treatment worldwide. 

Dendritic cells (DC) and macrophages exposed to live microfilariae in vitro show rednced matnration after M. tuberculosis infection, indicating a compromised activation of the immune system by mycobacteria upon co-infection with helminths (Talaat et al. 2006), thereby possibly reducing the susceptibility of DC for infection by M. tuberculosis. Thus, in vitro studies indicate that helminths can suppress the immune response to mycobacterial infections. However, the in vivo relevance of in vitro findings has to be more intensively examined. 

On this basis, the proteins of riboflavin biosynthesis may be relevant targets for the development of novel antibacterial agents, notably with selectivity for mycobacteria, Enterobacteriaceae, or pathogenic yeasts. Since these proteins are absent in human and animal hosts, the risks of off-target toxicity should be comparatively low. 

Loss-of-function polymorphisms in P2X7 are associated with impaired ability to kill mycobacteria via ATP in vitro (Saunders et al 2003, Fernando et al 2005). Monocytes from relevant subjects were differentiated into macrophages by adhesion, activated with IFNy, and then infected with M. bovis BCG at an MOI of 5. After two days, the cells were activated by brief exposure to ATP for 20 min and cultured for 16 h. The proportion of macrophages undergoing apoptosis was measured by staining for Annexin-V, and the degree of BCG killing relative to non-... 

The need for proper interpretation of the high tissue/serum ratios of macrolides and their clinical relevance have been recently reviewed [257-259]. Numerous studies have been published demonstrating intracellular uptake of macrolides. This phenomenon helps to explain their antimicrobial activity against many pathogens which reside in an intracellular environment, such as species of Legionella, Chlamydia, Salmonella, staphylococci, and mycobacteria. If the compound is bioavailable, high tissue concentrations of antibiotic would permit better eradication of infections localized within that tissue. 

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