One cannot rule them all: Are bacterial toxins-antitoxins druggable?

Chan, Wai Ting; Balsa, Dolors; Espinosa, Manuel

Despite all these possible approaches to be developed at a medium term, the everyday practice in hospitals need protocols to deal with infectious outbreaks that are easy and reliable to implement. Therefore, in addition to new antibacterials there is a need to develop translational research and interactions among healthcare cadres leading to direct and fluent communications between researchers, hospitals and the companies involved in drug development, e.g. knowledge transfer partnership. This, in due time, should lead to concepts such as drug-likeness approaches, so that the finding of novel bacterial targets and the drug development process could be expedited. It is also important to keep in mind the need to understand the biology of the bacterial species we are aiming, since biological and, especially, Figure 1 . Features of type II TAs. Typical type II TAs consists of two genes organized as an operon. The antitoxin gene precedes the toxin one. Both genes usually overlap and are co-transcribed from one or two promoters. TA genes encode both antitoxin (oval) and toxin (crescent) proteins that bind to each other and generate a harmless complex under normal conditions. The antitoxin protein also binds to its own promoter to negatively autoregulate the TA operon. The toxin protein is not able to bind to the promoter by itself, but serves as a co-repressor upon binding of the antitoxin to the promoter, to further repress transcription of the operon. Under stressful circumstances, the antitoxin protein which is more labile, is degraded more rapidly by the host proteases and thus liberate the toxin protein to act on the cell target. genetic approaches will be a significant aid in the drug discovery process (Trauner, Sassetti and Rubin 2014) .