Microbiologists would generally agree that the rapid rate at which microorganisms adapt to their environments, and in particular, to antimicrobial agents, is alarming. One may almost characterize the extreme immunity enjoyed of many microorganisms as an opposing army that only seems to get stronger when encountered by our best devices. It may seem frustrating to realize that our best defenses today will only harm us in the long run in the fight against invading microorganisms, but scientists at the Northwestern Institute on Complex Systems are looking to a new perspective to try to find the answers to the question, how to quell the negative influences of invasion. The scientists’ novel approach hinges on their view that the best way to see how microorganisms operate is to see how they influence biochemical pathways. By constructing networks in which nodes represent important metabolites and edges signify key enzymes, the scientists hope to characterize which enzymes are indeed necessary for the opposing microorganisms to utilize, thereby allowing one to narrow the field in the search for potential drug targets.

R. Guimera and M. Sales-Prado, who led the study, proceeded by constructing eighteen networks that featured connections between different molecules and metabolites through enzymes. In analyzing each network, they first sought to see the modularity of each node, or, more specifically, the degree of connectivity a particular node shares with other nodes. In reading their paper, one will see the expression the scientists used to determine such linkages, and they boast that it is the most effective current means of gauging modularity. The essence of such an investigation is to find precisely those nodes that contain many links, in hopes of using the metabolites they represent for therapeutic studies. They also sought to classify nodes according to their roles within a network. Their analyses included several different species, including E. coli and H. pylori, and in addition to their network characterizations, the scientists were also able to purport certain enzymes that are species-specific.

What is significant about Guimera and Sales-Prado’s study is their examination of indispensability: they quantified the degree to which the growth of a particular organism would be affected by the removal of a key enzyme. In doing so, they were able to identify at least a few enzymes are indeed crucial for the particular organism’s development; this revelation offers a potential opening for future, more focused studies.

One final interesting discovery in this paper was that some of the most essential pathways for some key processes in development are supported merely by fragile links. It is interesting to note that the very most deleterious effects of microorganisms may be answered by severing a few fragile edges. With all of these indicative theories on how molecules are related through enzymes, how some enzymes are established in networks, and, perhaps most strikingly, how the application of network theories to the biological world relays significant information on how nature actually works, the door is open to begin to find better therapies.

http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2149892&blobtype=pdf

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