Professor Jeff Cole, School of Biosciences, University of Birmingham
Monday 2nd December 2013, 4.00 p.m., Ingram Lecture Theatre
Bacteria are exposed to NO generated as an immediate product of nitrite reduction by denitrifying bacteria, from arginine by the mammalian NO synthetase, or as a by-product during nitrate reduction to ammonia. NO binds to di-iron and iron-sulphur clusters, inactivating many enzymes including aconitase and fumarase. This seminar will demonstrate that much of the literature about how bacteria protect themselves from this damage, or repair damage that has occurred, is incorrect. The Escherichia coli transcription factors NorR and NsrR bind NO specifically, triggering responses to nitrosative stress. NsrR is a repressor of genes required for NO reduction or damage repair, including the flavohemoglobin, Hmp, the hybrid cluster protein, Hcp, and the di-iron repair protein, YtfE. Hmp is an NO oxygenase. However, enteric bacteria do not live naturally in an aerated conical flask in a laboratory, but in the essentially anaerobic environment of the GI tract. Hmp expression is repressed by FNR, implying that it is not required during anaerobic growth. In contrast, Hcp expression is activated by FNR, suggesting it is important under anaerobic conditions. Hcp contains a [4Fe-2S-2O] hybrid cluster that is so far unique in evolution. Unique structure implies unique function and gene regulation usually reflects metabolic function: evidence will be presented that Hcp, not Hmp, is the critical factor in surviving nitrosative stress in vivo.