**6. Bacteriocins and phenotypic heterogeneity**

Colicins are bacteriocins, toxic proteins that are produced by and act against *E. coli* and its close relatives. Sensitive cells are killed by targeting DNA, RNA, cell membranes or by inhibition of peptidoglycan and lipopolysaccharide (LPS) O-antigen. Colicin genes are found within genomic clusters on colicinogenic plasmids. These clusters typically contain the colicin activity gene for the toxin, an immunity gene for a protein that confers self-resistance by binding to and inactivating the toxin protein, and a lysis gene for a protein that aids in colicin release by lysis of the producer cell [64]. Colicin production is found with high frequency among natural *E. coli* isolates [65].

Colicins are expressed from strong promoters whose activity is tightly repressed by the LexA protein. Nutrient limitation and DNA damage are major signals that control colicin production [64, 66]. Nevertheless, additional regulators, in conjunction with LexA, have been found to regulate/delay colicin expression. Thus, the global transcriptional factor, IscR, in response to the nutritional status of the cell and, co-dependently with LexA, delays induction of pore-forming colicin genes following SOS induction [67]. On the other hand, temporal induction of DNA and RNA targeting colicins is co-regulated by the AsnC repressor. At the colicin E8, *cea8* promoter, AsnC repression reflects L-asparagine levels and presumably serves as an indicator of general amino acid abundance and availability [68]. Thus, promoters of nuclease and pore-forming colicins have adopted different transcription regulators and specific metabolic inputs to regulate transcription in conjunction with the LexA repressor.

Colicins have an *in vivo* antagonistic role promoting microbial diversity within *E. coli* populations in the mammalian colon [69] and the potential to promote microbial genetic diversity [70]. Sublethal concentrations of ciprofloxacin have been shown to induce colicin expression in an SOS-dependent manner and imply that SOS-inducing antibiotics could thus affect microbial strain diversification, as well as promote the acquisition and dissemination of antibiotic resistance [71].

Furthermore, monitoring the transcriptional response of *E. coli* to colicins E9, an endonuclease, and E3, an RNase, has shown that the former induces the SOS response while the latter upregulates expression of DNA integrases, invertases, and recombinases. Colicins thus also have the potential to, through the induction of error-prone DNA polymerases, promote microbial diversity, gene transfer, DNA *The* Escherichia coli *SOS Response: Much More than DNA Damage Repair DOI: http://dx.doi.org/10.5772/intechopen.100353*

rearrangements affect horizontal gene transfer as well expression of virulence factor genes.

Colicin production has also been found to be a specialized function within a population of genetically identical cells, an example of phenotypic heterogeneity. The colicin K activity gene was shown to be expressed in only a small fraction of a population, while the immunity gene is expressed in the large majority of the cells [72]. A number of colicins are released semispecifically, by cell lysis. Differential expression of the activity and lysis genes prevents excessive lysis. Alternatively, upon DNA damage and induction of the SOS response, all cells express the activity gene. Lysis of the producer releasing colicin as well as lysis of the sensitive target cell, provides material for bacterial shielding or biofilm matrix as well as resources for growth for nonexpressing insensitive cells. A recent study showed ampicillin induced bacterial cell lysis provides a matrix of cell debris that shields viable cells from antimicrobial activity [18]. Further, lysed cells release molecules that could sequester antibiotics.

Subsequently, additional LexA regulated genes, including *lexA* and recA, were also shown to exhibit phenotypic heterogeneity with high level expression, in the absence of DNA damaging agents, in a small subpopulation of cells [73]. Heterogenous expression was found to be established primarily by stochastic factors and the binding affinity of LexA to SOS boxes. Heterogenous expression of *recA* and *lexA* genes could affect a number of phenomenon e. g., subpopulations with higher proficiency in recombination, antibiotic tolerance/persistence, horizontal gene transfer, prophage induction and virulence among pathogenic *E. coli* strains.
