Table 5.

Methods for identification of candidate microbial RNI resistance genes

Method	Examples	Ref.
Loss of function with in vitro selection (mutagenesis; selection for hypersusceptibility to RNI; complementation of mutant with library from wild type of same species)	metL	58
Loss of function with in vivo selection (differential signature tagged mutagenesis: comparison of recovery of transposon-mutagenized bacteria from wild-type mice, mice deficient in phox, mice deficient in NOS2 and mice deficient in both)	Underway
Gain of function (survival of recombinants expressing library from species of interest under selection pressure from RNIin vitro)	NOXR1, NOXR3	62, 63
Promoter trap (differential fluorescence induction or other in vivo expression technology to identify genes whose transcription is increased upon exposure to RNI)	Underway
Induction (detection of RNI catabolizing activity after sublethal exposure to RNI; purification monitored by bioactivity)	hmp (flavohemoglobin)	66
Biochemical hypothesis	SODC; ahpC	57, 68, 108