Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

Abstract

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).

Strategies for combating persister cell and biofilm infections

“…For example, 5-fluorouracil was utilized successfully in a human trial (Walz et al, 2010) and was given FDA approval for use to prevent biofilm formation on catheters (Angiotech Pharmaceuticals); 5-fluorouracil was discovered by screening 6,000 P. aeruginosa mutants for changes in biofilm formation and works by reducing cell communication (Ueda et al, 2009). 5-Fluorouracil was initially an FDA-approved for treating cancer (like mitomycin C and cisplatin), which illustrates another promising approach: repurposing drugs for antipersister and antibiofilm use (Soo et al, 2017). Therefore, given these exciting discoveries for treating the most recalcitrant infections, one can be sanguine about our ability to continue to make use of biotechnology for combating infections.…”

Targeting ADP-ribosylation as an antimicrobial strategy

“…However, despite the great efforts in developing anti-virulence compounds or in applying available PARP inhibitors for targeting ART activities involved in infectious diseases, the use of blocking antibodies still represents the gold standard treatment for neutralising bacterial toxins [63,64,[298][299][300].…”

The Glucosinolates, A Sulphur Glucoside Family of Mustard Phytochemicals With Diverse Biomedical Application

“…The repurposing of anticancer drugs for the treatment of bacterial infections has been suggested since some of these have proven to be effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria, other antibiotics have proved useful as anti-cancer compounds [55][56][57][58]. Among the most harmful human pathogenic bacteria, Staphylococcus aureus (Golden Staph) stands out as one of the most virulent and troublesome due to its ability to cause life-threatening infections and to adapt to changing environmental conditions [59,60].…”