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

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

New developments in drug delivery research are likely to have enormous economic impacts upon the pharmaceutical and biotechnology industries. In fact, drug delivery research represents a US$70 billion a year industry. Centres for Drug Delivery and Formulation have been established all over the world to promote research, development and training in drug delivery science. There has also been a focus on realizing the commercial potential of innovative molecules (e.g. peptides, nucleic acid based therapies and vaccines), or delivery technologies that are developed from the basic research centres. Thus, it is no wonder that a number of novel clever approaches have been proposed to deliver new drugs, as it has to be the case if bacterial toxins are going to be developed as antimicrobials. One interesting system, albeit still hypothetical, could be the employment of bacterial minicells for delivery ( Fig. 6 ; de la Cueva-Méndez 2013). Minicells are produced by bacteria defective in cell division; they lack chromosomal DNA, but plasmids do segregate into them and continue to be metabolically active. Thus, as early shown in many laboratories, ours among them (Espinosa, Lopez and Lacks 1984; Lacks et al., 1986) , plasmids in minicells are able to synthesize de novo the products they encode, including TA proteins, as shown for the kis-kid pair (Bravo, de Torrontegui and Díaz 1987; Bravo et al., 1988) . Plasmids encoding the desired TA construction will segregate into the minicells, making them good delivery candidates to the targeted cells (MacDiarmid et al., 2007) . We must remark that minicells do not seem to be appropriate enough for the treatment of bacterial infections as minicells will not be engulfed by prokaryotic cells; they could be envisaged, however, as useful delivery solutions for the treatment of cancer cells (MacDiarmid et al., 2007; de la Cueva-Méndez 2013) .