Fig. 4: Resistance to antifolates.
From: Profile and resistance levels of 136 integron resistance genes
a Folate biosynthesis pathway. FolP/DHPS condenses P-aminobenzoic acid (PABA) and 6-hydroxymethyl-7,8- dihydropterin pyrophosphate (DHPP) into 7,8 dihydropteroate (DHP). FolP is inhibited by sulfonamides (PABA analogs). DHP is then converted to 7,8 dihydrofolate (DHF) by the action of FolC/DHFS; which is again modified by the action of FolA/DHFR into 5,6,7,8-tetrahydrofolate (THF). The action of FolA/DHFR can be inhibited by the drug trimethoprim. Modified from63 b and c MIC of qacE∆sul1 and dfr cassettes against antifolate antibiotics. Antimicrobial resistance to sulfamethoxazole (SMX) (b) and trimethoprim (c) is shown as MIC (μg/mL) in the right axis, and resistance fold increase compared to the empty pMBA control in the left axis. The MIC is the mean of three biological replicates (black dots) for each strain. A red dotted line represents the clinical breakpoint (EUCAST) for E. coli against this antimicrobial. A hierarchical clustering tree showing protein sequence similarity is shown under the graph for trimethoprim.
