Figure 1616

Trimethoprim, Sulfonamides and the Folate Cofactor

Bacterial cells make folic acid, whereas, animal cells do not. The antibiotic sulfonamide is an analog of the p-aminobenzoic acid portion of folic acid. Trimethoprim is an analog of the dihydropteridine portion of folic acid. Both trimethoprim and sulfonamide bind to the biosynthetic enzymes and prevent synthesis of folic acid from its precursors.

Generally speaking, bacteria are most likely to attack their close relatives. The reason is that the more closely related they are, the more likely two strains of bacteria will compete for the same resources. Proteins made by bacteria to kill their relatives are known generally as bacteriocins. Particular bacteriocins are named after the species that makes them. So, for example, many strains of Escherichia coli deploy a wide variety of colicins, intended to kill other strains of the same species. [Since most work has been done on E. coli bacteriocins from other bacteria are often referred to as colicins although this is not strictly correct.] Surveys suggest that 10-15% of enteric bacteria make bacteriocins.

On several occasions, Yersinia pestis, the bacterium that causes Black Death (bubonic plague), has wiped out a third of the human population of Europe, and probably most of Africa and Asia. The virulence factors required for infection are carried on a series of plasmids (see below).As if this was not enough, Yersinia pestis also makes bacteriocins, called pesticins in this case, designed to kill competing strains of its own species.

bacteriocin Toxic protein made by bacteria to kill closely related bacteria colicin Toxic protein or bacteriocin made by Escherichia coli to kill closely related bacteria

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