**Abstract**

ABCB1 P-glycoprotein (P-gp) is an ATP-dependent efflux pump with broad substrate specificity associated with cellular drug resistance. Homologous to role in mammalian biology, P-glycoproteins of bacterial and fungal pathogens mediate the emergence of multidrug resistance phenotypes, with widespread clinical/ socioeconomic implications. This work aims to characterize P-gp homologues in certain WHO-prioritized infectious agents, namely (1) bacteria: *Acinetobacter baumannii* and *Staphylococcus aureus* and (2) fungi: *Aspergillus fumigatus*, *Candida albicans*, and *Cryptococcus neoformans*. PSI-BLAST searches against the genome of each of these organisms confirmed the presence of P-gp homologues. Each homologue was aligned against five known P-gp structures, for structural modeling. FDA-approved antibiotics used in the current line of therapy were retrieved from PubChem, and potential antibiotics were identified based on similarity and repurposing of the existing drugs. The most tenable target-ligand conformations from docking studies of the respective modeled P-gp structures and the antibiotic ligands were assessed for interacting residues within 4.5 Å of the ligand, probable binding pockets and relative efficacies of the new drugs. Our studies could lay the foundation for the development of effective synergistic or new therapies against these pathogens.

**Keywords:** P-glycoprotein, priority pathogen list, nosocomial infection, multidrug resistance, homology modeling, receptor-ligand docking, differential ligand affinity, synergistic effects
