IN REPLY TO: Is there any role for cAMP-CRP in carbon catabolite repression of the Escherichia coli lac operon? Reply from Görke and Stülke eJournal Correspondence
Martine Crasnier-Mednansky, Ph.D., D.Sc.
Copyright © 2008 Mednansky Institute, Inc.
Contact: martine [at] minst [dot] org

November 7, 2008

In a reply to my correspondence in Nature Reviews Microbiology, authors B. Görke and J. Stülke concluded that cAMP-CRP "is not directly involved in carbon catabolite repression (CCR) or in the glucose-lactose diauxie".  Basically they re-iterate the view set forth in their review on CCR (Görke B. 2008) that inducer exclusion, by blocking the entry of lactose, is the main contributor to CCR when wild type E. coli strains are growing in the presence of glucose and lactose.  In so doing they ignored crucial data and argumentation outlined in my correspondence titled: Is there any role for cAMP-CRP in carbon catabolite repression of the Escherichia coli lac operon? (Crasnier-Mednansky, 2008).  As such they jeopardized advancement of knowledge in the related field of research.

In their reply, the authors argued that cAMP levels on lactose are the same as the ones observed on glucose, in contrast with my statement that "the level of cAMP in lactose-grown cells is low compared with other less-preferred carbon sources, but nevertheless is slightly higher than the level of cAMP in glucose-grown cells".  To support their argumentation, they relied on an article by Bettenbrock K. 2007 reporting measurements of intracellular cAMP in E. coli, but ignored the contention by Bettenbrock K. 2007 that measuring intracellular cAMP concentrations in 'growing cells' is still not achieved in a reliable way due to active extrusion of cAMP.  They did not take into account experimental data indicating that phosphorylated Enzyme IIAGlc (which activates adenylate cyclase) is detected in lactose-grown cells but not in glucose-grown cells.  They further ignored the computation of data by Kremling A. 2007 which confirms differences in states of Enzyme IIAGlc phosphorylation during the glucose-lactose diauxie.

The authors also disregarded the article titled 'glucose lowers CRP* levels resulting in repression of the lac operon in cells lacking cAMP'.  They further disregarded the contention that use of a mutant strain insensitive to cAMP is not proper to address the issue at hand, an error that led to erroneous data interpretation by Hiroji Aiba and coworkers (Diauxie correspondence).

As regards abolition of the diauxic lag by exogenous cAMP,  the authors argued in their reply it is due to "an increased basal level of the lactose operon proteins".  However, this interpretation is not reconcilable with the proposal by Hiroji Aiba and coworkers that cAMP-CRP plays a crucial role in diauxie only by activating the transcription of the glucose transporter gene, as explained in my correspondence.

Finally the authors recognized in their reply that "different operon-specific mechanisms contribute to CCR, but these mechanisms and the level of their implication differ from system to system".  Would they consider the proposal that variation of cAMP levels in relation to the carbon source used for growth is actually a factor contributing to the extent of CCR in E. coli?