Anticancer Drugs as Antibiofilm Agents in Candida albicans: Potential Targets.

The human pathogen Candida albicans can grow as a biofilm on host tissues and on the surfaces of different prosthetic devices in a patient's body. Various studies have reported that biofilms formed by C. albicans are resistant to most of the currently used antibiotics including the widely prescribed drug, fluconazole. As such, novel strategies for the treatment of drug-resistant biofilms are required. Drug repositioning or the use of drugs outside their unique indication has the potential to radically change drug development. We have tested 16 anticancer drugs for their activities against C. albicans. For the first time, we are reporting repositioning of anticancer drugs as potential antibiofilm agents in C. albicans. Nine categories of drugs with different chemical modes of action effectively inhibited biofilms at a concentration range of 0.25-4 mg/mL, establishing their potential for the inhibition of biofilms. Human genes targeted by these drugs show significant identity with their homologous genes in C. albicans at the amino acid as well as nucleotide levels. This study indicates that anticancer drugs could be potential candidates for repositioning as anti-Candida biofilm agents.

The antibacterial agent, moxifloxacin inhibits virulence factors of Candida albicans through multitargeting.

Fluoroquinolines are broad spectrum fourth generation antibiotics. Some of the Fluoroquinolines exhibit antifungal activity. We are reporting the potential mechanism of action of a fluoroquinoline antibiotic, moxifloxacin on the growth, morphogenesis and biofilm formation of the human pathogen Candida albicans. Moxifloxacin was found to be Candidacidal in nature. Moxifloxacin seems to inhibit the yeast to Hyphal morphogenesis by affecting signaling pathways. It arrested the cell cycle of C. albicans at S phase. Docking of moxifloxacin with predicted structure of C. albicans DNA Topoisomerase II suggests that moxifloxacin may bind and inhibit the activity of DNA Topoisomerase II in C. albicans. Moxifloxacin could be used as a dual purpose antibiotic for treating mixed infections caused by bacteria as well as C. albicans. In addition chances of developing moxifloxacin resistance in C. albicans are less considering the fact that moxifloxacin may target multiple steps in yeast to hyphal transition in C. albicans.