2016 article comments:

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Sci Rep. 2016
The lag-phase during diauxic growth is a trade-off between fast adaptation and high growth rate
Chu D, Barnes DJ

It is astounding that the authors totally ignore the specific effects of cAMP on the lag phase of the glucose-lactose diauxie.  Not only does addition of cAMP eliminate the diauxic lag, it also clearly impairs growth on glucose (see figure 1 in Ullmann A, 1968).  An increased level of cAMP triggers a 'leaky' expression of CRP-cAMP-dependent genes and operons thereby affecting growth on glucose.  Leaky expression of genes reduces fitness in glucose, with a trade-off for a shorter diauxic lag (or, as in figure 1 mentioned above, a complete elimination of the lag phase resulting in biphasic growth).  In the Escherichi coli glucose-lactose diauxie, there is a correlation between the cAMP level and the cost-benefit trade-off.

This comment by M. Crasnier-Mednansky (martine [at] minst [dot] org) was originally posted on Feb 1, 2017 at PubMed Commons

Nucleic Acids Res. 2016
The target spectrum of SdsR small RNA in Salmonella
Fr÷hlich KS, Haneke K, Papenfort K, Vogel J

Expression of crp in Escherichia coli was found 'not to be' post-transcriptionally regulated by sRNAs including SdsR (Lee HJ, 2016).  In sharp contrast, this paper reports SdsR 'strongly' affects the expression of crp in Salmonella typhimurium.  What causes such discrepancy?

In all fairness, Lee HJ, 2016 noted "a few sRNAs (which included SdrS) were close to the twofold cutoff for repression of crp" and also noted "our translational fusions will only detect regulation in the 5’ UTR and the first 20 codons of the targets".  Therefore, it was prudently suggested that expression of crp was not affected by sRNAs.

Here, the authors observed a two-fold repression of crp by SdsR using whole genome microarray (Table 1), and an almost 2-fold repression using a gfp reporter fusion (Figure 1B).  Thus it appears there is no data discrepancy between the present work and Lee HJ, 2016.

The contention by the authors SdsR strongly affects the expression of crp is in relation to data obtained with sRNA CyaR (as reported in Figure 6).  Figure 6A indicates that, in early stationary phase, there is no synthesis of SdsR.  SdsR appears at +3h when the cells are supposedly well advanced in the stationary phase.  This suggests regulation by SdsR occurs late in the stationary phase, as mentioned by the authors.  Figure 6A also indicates constitutive SdsR is overly expressed, and most importantly the correlation between SdsR and crp mRNA is not straightforward, as observed by comparing lane 4 and 10 (or 11) in Figure 6A.

CyaR expression is positively regulated by CRP-cAMP (De Lay N, 2009), therefore a carbon source triggering a relatively high cAMP level as compared to glucose (maltose in this paper), caused an increase in the CyaR level both in the presence and absence of SdsR (Figure 6B, lane 1 to 8).  With SdsR overly expressed, the CyaR level significantly decreased for cells grown on maltose (Figure 6B, lane 11 and 12).  The authors concluded lack of CyaR is related to the repression of crp by SdsR yet the level of CRP was not monitored.

It is reasonable to conclude regulation of crp expression by sRNAs does not appear physiologically relevant during growth or entry into stationary phase.  However, this regulation may be significant upon accumulation of SdsR in nutrient-limited cells.  If this is the case, CRP-dependent synthesis of post-exponential starvation proteins, which are not essential for survival (Schultz JE, 1988), will gradually be shut off.  This attempted proposal is grounded in data from LÚvi-Meyrueis C, 2014 indicating lack of SdsR results in impaired competitive fitness however only after 2 to 3 days in stationary phase.

This comment by M. Crasnier-Mednansky (martine [at] minst [dot] org) was originally posted on Aug 4, 2016 at PubMed Commons

Mol Microbiol. 2016
Regulation of CsrB/C sRNA decay by EIIAGlc of the phosphoenolpyruvate: carbohydrate phosphotransferase system
Leng Y, Vakulskas CA, Zere TR, Pickering BS, Watnick PI, Babitzke P, Romeo T

This article is remarkable for demonstrating an interaction between unphosphorylated Enzyme IIA and the EAL domain of CsrD.  Such interaction is physiologically connected to the role of cAMP in Escherichia coli because there is an established correlation between the phosphorylation state of Enzyme IIAGlc and the level of cAMP, phosphorylation of Enzyme IIAGlc typically causing an increase in the cAMP level (and concomitantly eliminating the effect of Enzyme IIAGlc on CsrD).

The authors discussed the present regulatory interaction with no mention to the role of cAMP.  However, considering (1) the inhibitory function of (CsrD-controlled) CsrA on glycogen biosynthesis, (2) the ability of stationary-phase E. coli to accumulate glycogen as a carbon reserve, and (3) the increase in cAMP occurring upon entry into the stationary phase (Makman RS. 1965) (because of Enzyme IIAGlc rephosphorylation), it seems CsrD and CRP-cAMP both work 'in concert' for the timeliness of physiological processes during entry into stationary phase, particularly when cells are growing on glucose.

This comment by M. Crasnier-Mednansky (martine [at] minst [dot] org) was originally posted on Dec 14, 2015 at PubMed Commons

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