Tuesday, January 7, 2014

Sulfa drugs resistance mechanism reviled

How bacteria develop resistance towards sulfa drugs researchers reviles exact mechanism which could be used to design of new sulfa drugs which will not develop drug resistance.

Sulfa drugs are drugs were very useful as first line of therapy antimicrobial drugs until it developed drug resistance, it was observed that after some period bacteria became resistant to these class of drugs, and rendered these drugs less effective, replacing sulfa drugs with latest antibiotics. Still today for some type of infections sulfa drug are only important available drugs.

Scientists now have reveled exact mechanism with which bacteria produces resistance to sulfa drugs, they studied step wise mechanism of action of sulfa drugs by using X-ray crystallography.  

Sulfa drug inhibit enzyme dihydropteroate synthase (DHPS) in microorganisms , this enzyme is required in the biochemical reactions involving synthesis of folic acid, which is synthesized in bacteria for synthesis of cell wall, amino acids, enzymes, proteins, folic acid is synthesized from precursors Paraminobenzoic acid (PABA) and dihydropteridine pyrophosphate (DHPP), reaction is catalyzed by enzyme dihydropteroate synthase (DHPS) final product is folic acid .In human folic acid is derived from various food sources where as in bacteria it is required to be synthesized within bacterial cell for its survival.

Therefore inhibition of enzyme dihydropteroate synthase (DHPS) by sulfa drug kills bacteria , bacteria which produce resistance for sulfa drug develop mutations and changes in structure in enzyme dihydropteroate synthase (DHPS).Scientist have found that the change occur on active site on dihydropteroate synthase (DHPS) enzyme site, to study the exact mechanism they isolated enzyme dihydropteroate synthase (DHPS) and incubated with  Paraminobenzoic acid (PABA) and dihydropteridine pyrophosphate (DHPP), and studied the reaction in sequence with X-ray crystallography and found that there is a portion over enzymes active site where the sulfa drug do not fit completely.

Exploring this site and its structure will possibly enable us to develop more effective sulfa drugs which will not produce drug resistance.

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