Targeting Ocular Biofilms with Plant-Derived Antimicrobials in the Era of Antibiotic Resistance

Abstract

Microbial biofilms present a formidable challenge in ophthalmology. Their intrinsic resistance to antibiotics and evasion of host immune defenses significantly complicate treatments for ocular infections such as conjunctivitis, keratitis, blepharitis, and endophthalmitis. These infections are often caused by pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, particularly in patients using contact lenses or intraocular implants-devices that serve as surfaces for biofilm formation. The global rise in antimicrobial resistance has intensified the search for alternative treatment modalities. In this regard, plant-derived antimicrobials have emerged as promising candidates demonstrating broad-spectrum antimicrobial and antibiofilm activity through different mechanisms from those of conventional antibiotics. These mechanisms include inhibiting quorum sensing, disrupting established biofilm matrices, and interfering with microbial adhesion and communication. However, the clinical translation of phytochemicals faces significant barriers, including variability in chemical composition due to environmental and genetic factors, difficulties in standardization and reproducibility, poor water solubility and ocular bioavailability, and a lack of robust clinical trials evaluating their efficacy and safety in ophthalmic settings. Furthermore, regulatory uncertainties and the absence of unified guidelines for approving plant-derived formulations further hinder their integration into evidence-based ophthalmic practice. This review synthesizes the current knowledge on the pathogenesis and treatment of biofilm-associated ocular infections, critically evaluating plant-based antimicrobials as emerging therapeutic agents. Notably, resveratrol, curcumin, abietic acid, and selected essential oils demonstrated notable antibiofilm activity against S. aureus, P. aeruginosa, and C. albicans. These findings support the potential of phytochemicals as adjunctive or alternative agents in managing biofilm-associated ocular infections. By highlighting both their therapeutic promise and translational limitations, this review contributes to the ongoing discourse on sustainable, innovative approaches to managing antibiotic-resistant ocular infections.

Keywords: antimicrobial resistance; biofilm; ophthalmic infections; phytochemicals; phytotherapy.

Figure 1

Stages of biofilm formation. Biofilm development is a cyclical and regulated process initiated by the dispersal of bacterial cells from a pre-existing mature biofilm (I). These free-floating planktonic cells (II) actively migrate through the surrounding environment in search of favorable conditions. Upon encountering a solid surface (represented by the horizontal rectangle), they undergo reversible and then irreversible attachment (III), mediated by adhesins, surface appendages, and physicochemical interactions. This leads to the formation of early microcolonies (IV), accompanied by clonal expansion, quorum sensing activation, and the initial secretion of extracellular polymeric substances (EPS). As the structure matures (V), cells become embedded in a dense matrix composed of polysaccharides, proteins, lipids, and extracellular DNA. The resulting mature biofilm (VI) is a highly structured and resilient community exhibiting spatial heterogeneity, metabolic cooperation, and increased tolerance to antimicrobials. The cycle continues as a subpopulation of cells undergoes regulated dispersal.

Figure 2

Chemical structure of resveratrol.

Figure 3

Chemical structure of curcumin.

Figure 4

Chemical structure of abietic acid.

Figure 5

Chemical structures of the main constituents of essential oils.