Combating chronic bacterial infections by manipulating cyclic nucleotide-regulated biofilm formation
This article reviewed recent progress toward the development of drugs that interfere with c-di-GMP signaling as a route to control biofilm infections.
This special report, from researcher at the University of Dundee (UK) discusses cyclic nucleotide second messengers, in particular cyclic-di-GMP, signalling networks and control of bacterial biofilm development. The authors investigate recent progress toward the development of drugs that interfere with c-di-GMP signalling as a route to control biofilm infections and suggest cyclic nucleotide signalling is an emerging therapeutic target for the treatment of chronic bacterial infections.
Proof of concept studies have demonstrated that in P. aeruginosa, chemical agents and/or other strategies can be used to interfere or manipulate c-di-GMP signalling processes, such as synthesis or degradation of the nucleotide, disruption of its interactions with diverse cellular effectors, which in turn have an impact on biofilm formation and disease progression.
However, extensive advances in the area will still need to be achieve in order to see such an approach come to realization. Data from studies targeting known c-di-GMP singling elements should be considered for developing novel screens for inhibitory compounds. Detailed structural information is needed regarding the domains involved in c-di-GMP sensing which will form sensible design of molecules that inhibit or modulate c-di-GMP action. Importantly an emphasis will be required to see if such interference strategies function in the clinic.
Sources: An, S. Q. and R. P. Ryan (2016). "Combating chronic bacterial infections by manipulating cyclic nucleotide-regulated biofilm formation." Future Med Chem 8(9): 949-961.http://www.future-science.com/doi/abs/10.4155/fmc-...