# Unbridled Integons: A Matter of Host Factors
## 3 Host Factors Influencing the Expression of the Cassettes  
The vast majority of the integron cassettes do not carry any promoter, so their expression depends on the P\({}_{\rm C}\) promoter that is upstream of the cassettes. This promoter drives the expression of the cassettes according to a gradient so that expression levels are maximal for the first cassettes in the array, and they gradually decrease for those following, while the distal ones are not expressed [10; 15; 16; 17]. This feature is essential to maintain large arrays of cassettes at the lowest possible cost. This is particularly true for SCI, in which the array of cassettes can be gigantic. The SCI paradigm is that of _Vibrio cholerae_, termed Superintegron (SI), which contains about 180 cassettes. The expression of cassettes has been thoroughly studied in this species, and the corresponding P\({}_{\rm C}\) promoter is well characterized [18]. In particular, a CRP-cAMP binding motif [19] can be found in vicinity of the -35 box of the SI P\({}_{\rm C}\) promoter (Figure 3). This allows one to connect the expression of the cassettes to the host metabolism through the catabolic repression. It was found that in the SI, the cassette expression is not constitutive and that the activity of the P\({}_{\rm C}\) promoter is rather modulated by several factors, including the carbon source (low expression in presence of glucose and high expression in presence of succinate or arabinose) and the growth phase (low expression in exponential phase and high expression in stationary phase [20]). Interestingly, this means that CRP can integrate many metabolic signals, through its binding to cAMP and subsequent activation of P\({}_{\rm C}\) activity, to influence the range of cassettes that can be expressed in the SI. In conditions of metabolic stress that increase the cAMP levels in the cells, the gradient of expression of the SI cassettes will be extended, possibly favoring the expression of the appropriate combination of cassettes that will allow the cell to cope with the initial stress. Other factors such as temperature and salinity were also found to modulate cassette expression, but this is out of the scope of this review since we cannot assign such general stresses to a particular host factor, especially considering the fact that the general stress response regulator gene _rpoS_[21] was shown not to be involved in this process.  
P\({}_{\rm C}\) promoters of 3 of the 5 MI classes have been also characterized. The class 2 and 3 P\({}_{\rm C}\) promoters have a limited characterization [22; 23], but the class 1 P\({}_{\rm C}\) has been more extensively studied. Class 1 integrins are the main resistance cassette vectors in Gram negative bacteria, and they were found to carry many different variants of P\({}_{\rm C}\)[24], which have various strengths and confer different recombination properties to the IntI. Indeed, as the Pc promoter is embedded in the _intI_I gene, the Pc variants lead to differential amino acid substitutions within the _intI_I gene. This promoter has been found to be regulated by one nucleoid-associated protein (H-NS [25]); no CRP box could be found in any of these MI P\({}_{\rm C}\). Thus, if there is an interconnection between the metabolic state of the cell and the expression of the cassettes in the MI, it is an indirect one, and the CRP control seems to be a particularity of the SCIs. This marks the first difference of connectivity between the host and SCI or MI. For more details concerning the P\({}_{\rm C}\) integron promoters, you can refer to the review from [PERSON] and [PERSON] [26].