On 2017 May 22, Martine Crasnier-Mednansky commented:

The terminology 'induction prevention' does not apply to cAMP-dependent Carbon Catabolite Repression (CCR). It has been used to illustrate CCR in Bacillus subtilis, see figure 2 in Görke B, 2008. Escherichia coli cAMP-dependent CCR does not cause induction prevention. It is therefore incorrect to state: "The current model for glucose preference over other sugars involves inducer exclusion and induction prevention, both of which are strictly dependent on the phosphorylation state of EIIA^Glc in E. coli". Moreover, the major player in induction prevention is HPr, not EnzymeIIA^Glc.

Some referenced papers were misinterpreted by the authors. Lengeler J, 1972 reported, in wild type cells, induction of the mannitol operon 'is not prevented' by glucose. Lengeler J, 1978 reported expression of the mtl operon, in both constitutive and inducible strains, is 'resistant to CCR' caused by glucose. This expression was nearly insensitive to cAMP addition, even though expression of the mtl operon is dependent on cAMP (a cya mutant strain does not grow on mannitol). Hence, the level of cAMP in glucose-growing cells is probably sufficient for expression of the mannitol operon. It is unclear how the authors monitored CCR with their inducible strains, as data were not shown.

It was proposed induction of the mannitol operon may take place in the absence of PTS transport as follows. In the unphosphorylated state, transport of mannitol by Enzyme IICBA^Mtl (MtlA) occurred by facilitated diffusion, upon high-affinity binding of mannitol to the IIC domain Lolkema JS, 1990. Thus, the IIC domain appears as a transporter by itself translocating mannitol at a slow rate. This provides an explanation for the observations that (1) mutant strains lacking Enzyme I and/or HPr were still inducible by mannitol (which originally led to the proposal mannitol may be the inducer of the mannitol operon Solomon E, 1972) and (2) mutant strains lacking Enzyme IICBA^Mtl could not be induced unless mannitol was artificially generated in the cytoplasm. It was therefore concluded mannitol was the inducer of the mannitol operon. Interestingly, in the phosphorylated state, transport of free mannitol by Enzyme IICBA^Mtl can be detected on the condition that the transporter has a poor phosphorylation activity Otte S, 2003.

On 2017 May 22, Martine Crasnier-Mednansky commented:

The terminology 'induction prevention' does not apply to cAMP-dependent Carbon Catabolite Repression (CCR). It has been used to illustrate CCR in Bacillus subtilis, see figure 2 in Görke B, 2008. Escherichia coli cAMP-dependent CCR does not cause induction prevention. It is therefore incorrect to state: "The current model for glucose preference over other sugars involves inducer exclusion and induction prevention, both of which are strictly dependent on the phosphorylation state of EIIA^Glc in E. coli". Moreover, the major player in induction prevention is HPr, not EnzymeIIA^Glc.

Some referenced papers were misinterpreted by the authors. Lengeler J, 1972 reported, in wild type cells, induction of the mannitol operon 'is not prevented' by glucose. Lengeler J, 1978 reported expression of the mtl operon, in both constitutive and inducible strains, is 'resistant to CCR' caused by glucose. This expression was nearly insensitive to cAMP addition, even though expression of the mtl operon is dependent on cAMP (a cya mutant strain does not grow on mannitol). Hence, the level of cAMP in glucose-growing cells is probably sufficient for expression of the mannitol operon. It is unclear how the authors monitored CCR with their inducible strains, as data were not shown.

It was proposed induction of the mannitol operon may take place in the absence of PTS transport as follows. In the unphosphorylated state, transport of mannitol by Enzyme IICBA^Mtl (MtlA) occurred by facilitated diffusion, upon high-affinity binding of mannitol to the IIC domain Lolkema JS, 1990. Thus, the IIC domain appears as a transporter by itself translocating mannitol at a slow rate. This provides an explanation for the observations that (1) mutant strains lacking Enzyme I and/or HPr were still inducible by mannitol (which originally led to the proposal mannitol may be the inducer of the mannitol operon Solomon E, 1972) and (2) mutant strains lacking Enzyme IICBA^Mtl could not be induced unless mannitol was artificially generated in the cytoplasm. It was therefore concluded mannitol was the inducer of the mannitol operon. Interestingly, in the phosphorylated state, transport of free mannitol by Enzyme IICBA^Mtl can be detected on the condition that the transporter has a poor phosphorylation activity Otte S, 2003.