The identification of new and druggable targets in bacteria is a critical endeavour in pharmaceutical
research of novel antibiotics to fight infectious agents. The rapid emergence of resistant bacteria makes
today's antibiotics more and more ineffective, consequently increasing the need for new pharmacological
targets and novel classes of antibacterial drugs.
A new model that combines the singular value decomposition technique with biological filters comprised of
a set of protein properties associated with bacterial drug targets and similarity to protein-coding essential
genes of E. coli has been developed to predict potential drug targets in the Enterobacteriaceae family [1].
This model identified 99 potential target proteins amongst the studied bacterial family, exhibiting eight
different functions that suggest that the disruption of the activities of these proteins is critical for cells.
Out of these candidates, one was selected for target confirmation. To find target modulators, receptor-based
pharmacophore hypotheses were built and used in the screening of a virtual library of compounds. Postscreening
filters were based on physicochemical and topological similarity to known Gram-negative
antibiotics and applied to the retrieved compounds. Screening hits passing all filters were docked into the
proteins catalytic groove and 15 of the most promising compounds were purchased from their chemical
vendors to be experimentally tested in vitro.
To the best of our knowledge, this is the first attempt to rationalize the search of compounds to probe the
relevance of this candidate as a new pharmacological target
