MIeJCorrespondence

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

Martine Crasnier-Mednansky
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 Boris Görke and Jörg Stülke conclude 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 (Nat Rev Microbiol) 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 ignore 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? (PubMed).  As such they jeopardize advancement of knowledge in the related field of research.

In their reply Görke and Stülke argue 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 rely on an article by Bettenbrock et al. reporting measurements of intracellular cAMP in E. coli, but ignore the contention by Bettenbrock et al. that measuring intracellular cAMP concentrations in 'growing cells' is still not achieved in a reliable way due to active extrusion of cAMP (J Bacteriol).  They do 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 ignore the computation of data by Kremling et al. (BMC Syst Biol) which confirms differences in states of phosphorylation of Enzyme IIAGlc during the glucose-lactose diauxie.

Görke and Stülke also disregard the article titled 'glucose lowers CRP* levels resulting in repression of the lac operon in cells lacking cAMP'.  They further disregard 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 colleagues1.

As regards abolition of the diauxic lag by exogenous cAMP, it is indeed most likely because of "an increased basal level of the lactose operon proteins", as stated by Görke and Stülke in their reply.  However this interpretation is not reconcilable with the proposal by Hiroji Aiba and colleagues 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 Görke and Stülke recognize 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?

Footnotes:

1 Correspondence between PNAS Chief-Editor Randy Schekman and Chief Science Officer Martine Crasnier-Mednansky Diauxie correspondence

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