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

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

Persistence poses significant challenges for the treatment of bacterial infections such as latent infections and post-treatment relapse; and biofilm also raises problem by forming a host for the survival of persisters (Lewis 2007 (Lewis , 2008 (Lewis , 2010 Zhang et al., 2014) . Knowing that activation of TAs increases persisters and that most of the common antibiotics kill only growing bacteria, we could conjecture to turn the risk into opportunity: reduce bacterial cell growth and increase persister cells formation by activation of TAs, and then treat the persister cells with persister drug-like PZA. PZA is an unconventional persister drug for tuberculosis that only act on non-growing persister cells at acidic condition. It has shortened the tuberculosis treatment period from 9-12 months to 6 months by killing the subpopulation of persisters that are not killed by the tuberculosis drug (Zhang et al., 2014) . Consequently, in line with the development of TAs as antibacterials, new drugs that target persisters should also be developed. Other approaches that deal with persisters could be 'waking up' the persisters, enhance activities of antibiotics and harness the host immune system (reviewed by Zhang et al., 2014) .