Table 1.

Mutations potentially contributing to reduced susceptibility and/or resistance to metronidazole (MTZ) in C. difficile.

Gene/Protein implicated	Potential Contribution to Metronidazole Resistance	Ref.
Ferric uptake regulator (fur)	Point mutation could lead to altered binding of Fur to SOD therefore reduced oxidative stress in C. difficile in response to MTZ exposure.	[97,98]
Putative nitroreductase	Frameshift mutation could affect activation of MTZ.	[98]
Coproporphyrinogen III Oxidase (hemN)	Frameshift mutation could disrupt heme biosynthesis/metabolism, defective electron transport and reduced MTZ activation.	[98]
Ferritin	Absence in MTZR strain under MTZ pressure therefore deficient iron storage	[99]
Butyryl CoA dehydrogenase (Bcd)	Significant reduction under MTZ pressure, therefore possible reduced ferredoxin reduction and consequent reduction in MTZ activation.	[99]
Ferredoxin (2 proteins)	Reduced expression in MTZR and revertant strains, possible reduction in MTZ activation. Another ferredoxin protein was increased in expression in MTZR and revertant strains. Unclear significance.	[97]

MTZ_R = metronidazole-resistant C. difficile.