Trimethoprim and brodimoprim resistance of gram-positive and gram-negative bacteria.
Trimethoprim and brodimoprim act by selectively inhibiting bacterial dihydrofolate reductase. There are a number of mechanisms by which bacteria can develop resistance to these agents. These include thymineless mutation, impermeability, alteration in chromosomal dihydrofolate reductase and the plasmid-encoded production of an additional dihydrofolate reductase which is insensitive to inhibition by antifolate agents. Clinically the most important of these is the plasmid-encoded production of additional dihydrofolate reductases and such resistance is found in both gram-positive and gram-negative species. These plasmid-encoded enzymes were initially divided into a number of classes based principally on their biochemical profiles. More recently sequence analysis has been used to study these proteins and thus the classification of dihydrofolate reductases now also takes into account sequence information. The number of plasmid-mediated dihydrofolate reductases has increased markedly in recent years. Whilst this probably results from the continuing evolution of resistance it can also be partly attributed to more discriminatory methods for studying these enzymes.
Thomson
C J
CJ
Department of Medical Microbiology Medical School, University of Edinburgh.
D005493:Folic Acid Antagonists; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000494:pharmacology; D014296:Trimethoprim Resistance / Q000502:physiology*
D005493:Folic Acid Antagonists; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase; C037079:brodimoprim