1.C.103 The Pore-forming Toxin, TisB (TisB) Family
The bacterial peptide, TisB, is involved in persister cell formation in E. coli. TisB and its analogs form multi-state ion-conductive pores in planar lipid bilayers with all states displaying similar anionic selectivity. TisB analogs differing by ±1 elementary charges show corresponding changes in ion selectivity. Probing TisB pores with poly-ethylene glycols revealed only restricted partitioning even for the smallest polymers, suggesting that the pores are characterized by relatively small diameters. Gurnev et al. (2012) suggested that TisB forms clusters of narrow pores that are essential for its mechanism of action in arresting growth and promoting the formation of non-growing persister cells. TisB is found in several enterobacteria.
TisB is a toxic peptide of 29aas; overexpression causes cessation of growth and induces a stress-response. A number of membrane protein genes are expressed, leading to cell death. Part of the programmed response to DNA damage leads to increased accumulation of TisB which slows or stops bacterial growth, probably allowing DNA repair before cells continue to grow (Wagner and Unoson 2012).
TisB is part of the SOS-response regulon, controlled by LexA. The sRNA IstR-1 inhibits toxicity by sequestering the standby ribosome binding site for tisB; as the levels of IstR-1 decrease, this site opens, and ribosomes are able to bind to initiate translation further downstream. It is therefore a type 1 toxin/antitoxin (TA) system, where expression of the proteinaceous toxin is controlled by an antisense sRNA.
Competition experiments between isogenic strains with or without the TisB/IstR-1 region revealed that in the presence of DNA-damaging agents, deletion strains were disadvantaged and were almost extinct by 4 days (Wagner and Unoson 2012). Originally TisA and TisB were fused into one ORF by frameshift reconstruction. TisA is probably a pseudogene.
Moderate expression reduces the pmf and causes dormancy in the form of persister cells (Lewis, 2010). Ciprofloxacin induces tisB expression and the formation of perisisters (Dörr et al., 2010). It also reduces stress responses. The antitoxin, IstR-1, together with TisB, comprise a typical type I toxin/antitoxin system. Transcription is controlled by an antisense sRNA (Unoson and Wagner, 2008). TisB homologues are present in Escherichia, Salmonella, Citrobacter, and Klebsiella strains.