Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections.

Despite the fact that bacterial infections are one of the leading causes of death worldwide and that mortality rates are increasing at alarming rates, no new antibiotics have been produced by the pharmaceutical industry in more than a decade. The situation is so dire that the World Health Organization warned that we may enter a "post-antibiotic era" within this century; accordingly, bacteria resistant against all known antibiotics are becoming common and already producing untreatable infections. Although several novel approaches to combat bacterial infections have been proposed, they have yet to be implemented in clinical practice. Hence, we propose that a more plausible and faster approach is the utilization of drugs originally developed for other purposes besides antimicrobial activity. Among these are some anticancer molecules proven effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria; some of which also protect animals from infections and recently are undergoing clinical trials. In this review, we highlight the similarities between cancer cells/tumors and bacterial infections, and present evidence that supports the utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some promising properties such as broad activity (all three compounds), dual antibiotic and antivirulence properties (5-FU), efficacy against multidrug resistant strains (Ga), and the ability to kill metabolically dormant persister cells which cause chronic infections (mitomycin C).

Role of quorum sensing in bacterial infections.

Quorum sensing (QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed.

Drug repurposing as an alternative for the treatment of recalcitrant bacterial infections.

Bacterial infection remains one of the leading causes of death worldwide, and the options for treating such infections are decreasing, due the rise of antibiotic-resistant bacteria. The pharmaceutical industry has produced few new types of antibiotics in more than a decade. Researchers are taking several approaches toward developing new classes of antibiotics, including (1) focusing on new targets and processes, such as bacterial cell-cell communication that upregulates virulence; (2) designing inhibitors of bacterial resistance, such as blockers of multidrug efflux pumps; and (3) using alternative antimicrobials such as bacteriophages. In addition, the strategy of finding new uses for existing drugs is beginning to produce results: antibacterial properties have been discovered for existing anticancer, antifungal, anthelmintic, and anti-inflammatory drugs. In this review, we discuss the antimicrobial properties of gallium compounds, 5-fluorouracil, ciclopirox, diflunisal, and some other FDA-approved drugs and argue that their repurposing for the treatment of bacterial infections, including those that are multidrug resistant, is a feasible strategy.