💊Sulfamethoxazole and trimethoprim (Septra)

October 18, 2019 - 2 min read 🍵

Tags: lifebiochemistry

What is Septra?

Septra or Sulfamethoxazole and trimethoprim is a combination of two antimicrobial agents that work against a wide variety of infections, ranging from ear infections to urinary tract infections.

How does Septra work?

It works by inhibiting an enzyme called dihydrofolate reductase (DHFR) in bacteria and inhibiting a bacterial enzyme called dihydropteroate synthase (DHPS). Since bacteria possess a distinct DHFR enzyme, sulphonamides and trimethoprim produce a synergistic effect by simultaneous binding to bacterial dihydropteroate synthetase and dihydrofolate reductase respectively[1][2]. The inhibition prevents the bacterial synthesis of tetrahydrofolic acid (THF) which is essential to make both purines and pyrimidines - the building blocks of DNA. By preventing bacteria from producing DNA, they are unable to reproduce and grow[3].

What is dihydrofolate reductase (DHFR)?

Dihydrofolate reductase is an enzyme that reduces folic acid to make dihydrofolic acid (DHF) and then can be further reduced again to make tetrahydrofolic acid (THF) [4].

Folic acid is a common form of folate which is an essential vitamin (B9) that is used to make DNA and RNA and is responsible for the metabolism of amino acids[3]. Mammals cannot synthesize folic acid as it is only obtained through diet, thus, making it an essential vitamin. The use of folic acid is used derive THF which is an active cofactor used in many biochemical reactions.

What is dihydropteroate synthase (DHPS)?

Sulfonamides act as a competitive inhibitor to a bacterial enzyme called DHPS which is involved in the synthesis of folate. Since mammals cannot synthesize folic acids, they do not have this metabolic pathway and therefore are unaffected by sulfonamides. This makes sulfomamides a safe antibiotic by reducing the disruption of mammal biochemical pathways. When bacteria try to use DHPS to make folate for DNA, they will have a hard time due to sulfonamides blocking the active sites of DHPS[5].

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