Pathogen Adaptation Potential

Another important question concerns pathogen adaptation potential. In particular, the redundancy in enzymatic pathways allows pathogens to escape antibiotic attack or inhibition of enzyme activities. To calculate metabolic capabilities in this respect, elementary mode analysis (see above) [5] is useful: the elementary modes are the basic metabolic paths in the metabolic network. Scrutinizing the list of calculated modes for a specific pathogen reveals which metabolites require which enzymes for their synthesis. Consideration of subnetworks makes this analysis easier [43]. In some cases the metabolic web of a pathogen allows the compounds required for growth to be produced by alternative routes. However, some key enzymes can be singled out which either are central for many paths or are unique in their capabilities and no detour around their blockage is possible. Similarly, the capabilities for metabolic adaptation to a wide range of environmental conditions can be estimated using elementary mode analysis.

Another way to look at enzyme flexibility in pathogens is a more comprehensive evolutionary perspective. Here all our data [26, 44, 45] indicate that widespread recruitment to new pathways allows pathogens to cope within surprisingly few generations with new pathways to fight new man-made antibiotics.

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