coli populations in the mammalian colon [9, 74]. Furthermore, the nuclease colicins, E9 and E3, have been shown to have the potential to promote microbial genetic diversity via induction of the SOS response or via increased transcription

of laterally acquired mobile elements, respectively [75]. Another study showed that colicins from one producer can induce production in another producer, thus Birinapant resulting in colicin-mediated colicin induction [74]. Here, we show that subinhibitory concentrations of colicin M induced an envelope and other stress responses including TPX-0005 in vivo the two component CreBC system connected with increased resistance to colicins M and E2. In natural environments, subinhibitory concentrations of colicin M could thus affect E. coli bacterial communities by promoting ecological adaptation enabling noncolicinogenic cells to survive and compete with colicin producers. The above-described phenomena might also be relevant in the natural settings of other bacterial species,

as colicin M homologous proteins have been identified recently in human and plant pathogenic Pseudomonas species that have hydrolytic activity against peptidoglycan precursors [76]. Further, activation of the P. aeruginosa CreBC system has been shown to play a major role in the ß-lactam resistance response [44]. Resistance of pathogens to traditional antibiotics represents one of the greatest health care threats. see more The present lack of novel antibiotics is also of great concern. Colicin M has been recently shown to hydrolyse lipid II intermediates of Gram-negative and Gram-positive bacteria Sirolimus [12]. In addition, as the isolated colicin M catalytic domain displays full enzymatic activity, protein engineering can be used to allow binding and translocation in various Gram-negative and Gram-positive species [77, 78]. Furthermore,

low concentrations and low protein-to-bacteria ratios suffice for colicin M to kill E. coli. Targeting of lipid II has been indicated as a potential antibacterial strategy [79]. Conclusion In conclusion, subinhibitory concentrations of colicin M induced genes involved in adaptive responses to protect the population against envelope and other stresses, including the two component CreBC system associated with increased resistance to some colicins. Our study of the global transcriptional response to colicin M thus provides novel insight into the ecology of colicin M production in natural environments. While an adaptive response was provoked by colicin M treatment there was no induction of biofilm formation, SOS response genes, or other genes involved in mutagenesis, adverse effects shown to be promoted by a number of clinically significant traditional antibiotics.