1 3 Arch Microbiol (2014) 196:753–764 DOI 10.1007/s00203-014-1017-8 ORIGINAL PAPER The role of stress in colicin regulation Lusine Ghazaryan · Lilit Tonoyan · Ashraf Al Ashhab · M. Ines M. Soares · Osnat Gillor Received: 24 February 2014 / Revised: 5 July 2014 / Accepted: 11 July 2014 / Published online: 22 July 2014 © Springer-Verlag Berlin Heidelberg 2014 Introduction Bacteriocins are biologically active proteins found in all major lineages of bacteria and archaea (Torreblanca et al. 1994; Riley and Wertz 2002). The bacteriocin fam- ily includes proteins that vary in size, microbial targets and mode of action. Nevertheless, all share two major fea- tures: They are ribosomally synthesized, and they have a relatively narrow killing spectrum. In fact, bacteriocins are lethal only to bacteria that are closely related to the produc- ing strain and are competing for the same limited resources and space (Riley and Wertz 2002). The most extensively studied bacteriocins produced by gram-negative bacteria are the colicins, the bacteriocins pro- duced by Escherichia coli (Riley and Wertz 2002; Cascales et al. 2007). Many aspects of colicins’ biochemistry, regu- lation, ecology and evolution have been explored (Cascales et al. 2007) since their discovery in 1925 (Gratia 2000). In general, colicins share two key features (Table 1): Their syn- thesis is encoded by an operon, and the operon is harbored in a plasmid (Braun et al. 1994; Cascales et al. 2007). Col- icin-encoding plasmids are divided into two main groups according to their size, amplification rate, number of copies per cell and ability for independent transfer by conjugation. The first group includes small (6–10 kb), low-copy-number plasmids (10–20 copies per cell) that replicate but are inca- pable of independent transfer by conjugation. The second group consists of large mono-copy plasmids (40 kb) that can often be transferred by conjugation (Cascales et al. 2007). The colicinogenic plasmids harboring gene clusters are com- posed of a colicin gene (cxa for colicin X), which encodes the toxin, an immunity gene (cxi) encoding the protein that confers specific protection on the colicin-producing cell and, sometimes, a lysis gene (cxl), which encodes a lysis protein involved in colicin release (Cascales et al. 2007). Abstract Bacteriocins produced by Enterobacteriaceae are high molecular weight toxic proteins that kill target cells through a variety of mechanisms, including pore for- mation and nucleic acid degradation. What is remarkable about these toxins is that their expression results in death to the producing cells and therefore bacteriocin induction have to be tightly regulated, often confined to times of stress. Information on the regulation of bacteriocins pro- duced by enteric bacteria is sketchy as their expression has only been elucidated in a handful of bacteria. Here, we review the known regulatory mechanisms of enteric bacteriocins and explore the expression of 12 of them in response to various triggers: DNA-damaging agents, stringent response, catabolite repression, oxidative stress, growth phase, osmolarity, cold shock, nutrient depriva- tion, anaerobiosis and pH stress. Our results indicate that the expression of bacteriocins is mostly confined to muta- genic triggers, while all other triggers tested are limited inducers. Keywords Colicin · SOS regulation · Luciferase reporter · Microscopy Communicated by Erko Stackebrandt. Electronic supplementary material The online version of this article (doi:10.1007/s00203-014-1017-8) contains supplementary material, which is available to authorized users. L. Ghazaryan · L. Tonoyan · A. A. Ashhab · M. I. M. Soares · O. Gillor (*) Zuckerberg Institute for Water Research, J. Blaustein Institutes for Desert Research, Ben-Gurion University, 84990 Midreshet Ben-Gurion, Israel e-mail: gilloro@bgu.ac.il