A Systematic In Silico Analysis of the Legionellaceae Family for Identification of Novel Drug Target Candidates.

The family Legionellaceae consists of Gram-negative bacteria that are widely distributed in aquatic environments around the world. This family consists of a single genus, Legionella, that is recognized as an important cause of community-acquired pneumonia and hospital-acquired pneumonia. Legionella consists of intracellular pathogens, thus cellular pharmacokinetic and pharmacodynamic properties of an antibiotic against these bacteria as well as uptake and subcellular distribution into macrophages should be considered for a successful outcome of disease. Treatment strategies for Legionella infection require a combination of multiple antibiotics. Hence, because of the possible development of resistance to the drugs during therapy, a new alternative targeted therapy is yielding promising results. In this study, a comprehensive in silico target identification pipeline was performed on members of the family Legionellaceae to identify the best targets. Using a homology-based computational pipeline method, new drug targets were identified. Of 4,358 analyzed proteins, 18 proteins, including proteins involved in metabolism (amino acid, energy, and lipid metabolisms), cellular transport, cell division, and cell motility, were selected as the final putative drug targets. These proteins play an important role in the survival and propagation of Legionella infection. In conclusion, homology-based methods could improve the identification of novel drug targets and the drug discovery process, which can potentially be effective for the prevention and treatment of Legionella infections.

Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family: A Homology-Based Method.

The Enterobacteriaceae is a large family of Gram-negative, facultative anaerobic, non-spore forming rod-shaped bacteria that includes harmless and pathogenic organisms. The emergence and development of drug resistance in Enterobacteriaceae is complicating the treatment of serious infections. The aim of this study is to predict and characterize putative drug targets in Enterobacteriaceae family employing a homology-based computational method. The final putative drug targets were qualitatively characterized via cellular function prediction, subcellular localization prediction, broad-spectrum, and druggability analyses. Of 6,327 analyzed proteins, 35 proteins were selected as final putative drug targets in Enterobacteriaceae family. These putative drug targets were involved in different vital pathways like metabolism, biosynthesis of macromolecule, and cell division. Predicted drug targets were also localized in the cytoplasm and cytoplasmic membrane of the pathogen that acts as antimicrobial or vaccine targets. Of 35 drug targets, 5 targets were druggable and 30 targets were not druggable and were predicted as novel drug targets, which should be further evaluated to develop new antimicrobial. Thirteen drug targets were considered as broad-spectrum targets. It is expected that results of our study could facilitate the production of novel antibacterial for efficient treatment of infections caused by Enterobacteriaceae pathogens.