Significance: An increasing number of pathogens are acquiring resistance to antibiotics. Efficient antimicrobial drug regimens are important even for the most advanced therapies, which range from cutting-edge invasive clinical protocols, such as robotic surgeries, to the treatment of harmless bacterial diseases and to minor scratches to the skin. Therefore, there is an urgent need to survey alternative antimicrobial drugs that can reinforce or replace existing antibiotics. Recent Advances: Bacterial proteins that are critical for energy metabolism, promising novel anticancer thiourea derivatives, and the use of synthetic molecules that increase the sensitivity of currently used antibiotics are among the recently discovered antimicrobial drugs. Critical Issues: In the development of new drugs, serious consideration should be given to the previous bacterial evolutionary selection caused by antibiotics, by the high proliferation rate of bacteria, and by the simple prokaryotic structure of bacteria. Future Directions: The survey of drug targets has mainly focused on bacterial proteins, although host signaling molecules involved in the treatment of various pathologies may have unknown antimicrobial characteristics. Recent data have suggested that small molecule inhibitors might enhance the effect of antibiotics, for example, by limiting bacterial entry into host cells. Phagocytosis, the mechanism by which host cells internalize pathogens through β-actin cytoskeletal rearrangement, induces calcium signaling, small GTPase activation, and phosphorylation of the phosphatidylinositol 3-kinase-serine/threonine-specific protein kinase B pathway. Antioxid. Redox Signal. 34, 486-503.
Keywords: ROS; antibiotics; bacterial entry; novel antimicrobial drugs; pathogen; signal transduction in cancer.