Interactions between Human Phagocytes and Candida albicans Biofilms Alone and in Combination with Antifungal Agents

Candida albicans is the most common cause of vascular catheter-related candidemia [1, 2]. Implanted medical devices, such as intravascular catheters are highly vulnerable to infection [3, 4]. Biofilms are a critical virulence determinant in such infections. Recently published guidelines by the Infectious Diseases Society of America recommend catheter removal in case of infection of central venous catheters with Candida [5]. However, this is not always effective or feasible [6]. Candida albicans biofilms constitute complex, three-dimensional ultrastructures, with distinctive developmental phases. Fully established Candida biofilms consist of a dense network of yeasts, hyphae and pseudohyphae embedded in a matrix of polysaccharides, proteins and other as yet undefined components [7, 8]. One of the principal characteristics of biofilms is their resistance to commonly used antifungal agents [9, 10]. By comparison to their planktonic (free-floating) counterparts, Candida biofilms are particularly resistant to azoles and amphotericin B but remain susceptible to the newly introduced echinocandins that target cell wall β-glucan biosynthesis [9, 11, 12]. While previous studies have examined the interactions between human phagocytes and planktonic Candida spp. [13], the corresponding phagocyte-biofilm interactions, are largely unknown. Chandra et al first addressed the role of host immune cells in the growing Candida biofilm [14]. However, it is unknown how Candida within the established biofilm responds to phagocytes. Similarly, it is unknown how antifungal agents interact with phagocytic cells against Candida biofilms. Whether the differential antifungal drug class activity could influence the host-cell interactions with biofilms is also unclear. To address these questions, we investigated the interactions between C. albicans biofilms and polymorphonuclear leukocytes (PMNs) as well as monocytes (MNCs) alone and in combination with voriconazole (VRC) or anidulafungin (ANID).