Global transcriptional responses to the bacteriocin colicin M in Escherichia coli

Abstract

BackgroundBacteriocins are protein antimicrobial agents that are produced by all prokaryotic lineages. Escherichia coli strains frequently produce the bacteriocins known as colicins. One of the most prevalent colicins, colicin M, can kill susceptible cells by hydrolyzing the peptidoglycan lipid II intermediate, which arrests peptidoglycan polymerization steps and provokes cell lysis. Due to the alarming rise in antibiotic resistance and the lack of novel antimicrobial agents, colicin M has recently received renewed attention as a promising antimicrobial candidate. Here the effects of subinhibitory concentrations of colicin M on whole genome transcription in E. coli were investigated, to gain insight into its ecological role and for purposes related to antimicrobial therapy.ResultsTranscriptome analysis revealed that exposure to subinhibitory concentrations of colicin M altered expression of genes involved in envelope, osmotic and other stresses, including genes of the CreBC two-component system, exopolysaccharide production and cell motility. Nonetheless, there was no induction of biofilm formation or genes involved in mutagenesis.ConclusionAt subinhibitory concentrations colicin M induces an adaptive response primarily to protect the bacterial cells against envelope stress provoked by peptidoglycan damage. Among the first induced were genes of the CreBC two-component system known to promote increased resistance against colicins M and E2, providing novel insight into the ecology of colicin M production in natural environments. While an adaptive response was induced nevertheless, colicin M application did not increase biofilm formation, nor induce SOS genes, adverse effects that can be provoked by a number of traditional antibiotics, providing support for colicin M as a promising antimicrobial agent.

Response of Extraintestinal Pathogenic Escherichia coli to Human Serum Reveals a Protective Role for Rcs-Regulated Exopolysaccharide Colanic Acid

“…The transcriptional response to bactericidal serum observed in this study was strikingly similar to that reported previously in E. coli treated with ␤-lactam antibiotics and colicin M (48,49). These have a common target in synthesis of peptidoglycan (PG).…”

The Pseudomonas aeruginosa CreBC Two-Component System Plays a Major Role in the Response to β-Lactams, Fitness, Biofilm Growth, and Global Regulation

“…No phenotypic changes were observed for the multiple creABCD mutants analyzed, but significant differences were observed for the cbrA and cbrBC double mutants. In- terestingly, subinhibitory concentrations of colicin M induce the transcription of genes involved in adaptive responses, including the two-component CreBC system associated with increased resistance to some colicins (45). Recent studies have demonstrated that CbrA, being a nonessential protein, confers high resistance to colicin M and renders cells resistant to osmotic shock in a CreBCdependent manner (46).…”

Novel Genes and Regulators That Influence Production of Cell Surface Exopolysaccharides in Sinorhizobium meliloti

“…We postulate that increased production of EPS-I in these mutants is part of a peptidoglycan stress response. Such a response has not been characterized in rhizobia previously, but in response to peptidoglycan-targeting antibiotics, E. coli and Pseu-domonas aeruginosa increase production of the exopolysaccharides colanic acid and alginate, respectively (75,76). If peptidoglycan stress triggers EPS-I production in S. meliloti, it could explain the EPS-I phenotypes of the cbrA and podJ cell division mutants (53,77).…”