FIG 8.

Model of the activation of expression and function of MdaB and NfrA by RrpA and RrpB. Structurally diverse quinones (Q) and flavins (F) produced by other bacteria in the intestinal microbiota or other environments encountered by C. jejuni enter the cell, where they easily abstract single electrons from the flavins or metal centers of cellular redox enzymes (62) to form partially reduced semiquinones (SQ) or flavo-semiquinones (FSQ). In the presence of molecular oxygen, these can lead to the formation of toxic superoxide and other ROS (hydrogen peroxide), which may be dealt with by superoxide dismutase, catalase, and thiol peroxidases (AhpC, Tpx, and Bcp). Elevated ROS leads to oxidation of Cys13 of RrpA and Cys8 of RrpB, although the exact species which effects this oxidation is not known. It is also possible that Q/F-Cys adduct formation (by Michael addition) occurs (dashed lines). Oxidized/modified RrpA C13 to C13-SO₂H leads to an increased activation of the divergently transcribed gene mdaB, leading to production of MdaB, which is a quinone reductase that can fully reduce quinones to quinols (HQ) by two-electron transfer from NADPH. RrpB is a negative regulator of the divergently transcribed nfrA gene, encoding an NADPH-dependent flavin reductase (NfrA). We presume that oxidation/modification of RrpB C8-SH produces a C8-SO₂-SH and C8-Dha (dehydroalanine) which destabilizes the dimer and, in turn, leads to the derepression of nfrA expression, allowing NfrA to catalyze the formation of fully reduced flavin hydroquinone (FHQ). The two-electron transfer catalyzed by both MdaB and NfrA avoids the semiquinone-mediated production of ROS. It is not known if or how cycling back to the oxidized forms occurs. This mechanism leads to a decrease in the toxic threat from exogenous quinones and flavins, but it comes at the expense of a drain on the cellular NADPH pool.