Mevalonate-independent pathway of isoprenoids synthesis: A potential target in some human pathogens

摘要

The rapidly increasing resistance of many human pathogens to all currently available drugs has become a serious health problem around the globe. Among these pathogens, Mycobacterium tuberculosis still poses a major human threat causing tuberculosis in the lung, and is responsible for more than one-quarter of all preventable adult deaths in the world. In addition, the emergence of various multidrug resistance mycobacterial strains, generates an urgent demand for novel therapeutic approaches. Another leading human pathogen, Plasmodium falciparum causing malaria, also accounts for one of the world's worst health problems leading to 1.5 to 2.7 million deaths annually. These deaths are primarily among the children and pregnant women. Helicobacter pylori, a human gastric pathogen, is an etiologic agent of chronic active gastritis, peptic ulcer disease, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma; 70 to 90 percent of the population in developing countries carries this pathogen. Therefore, it has become more important to understand the operation of various metabolic pathways existing in these pathogens, to find a suitable target that can be used in developing drugs against them. One such metabolic process occurring in these microorganisms is that they all utilize the same common mevalonate-independent (non-MVA) pathway of isoprenoids synthesis that was first discovered by Rohmer and coworkers in the early nineties, while studying the biosynthesis of hopanoids (a pentacyclic triterpenic sterol surrogates) from different bacterial species.