Impact of nanosystems in Staphylococcus aureus biofilms treatment

Abstract

Staphylococcus aureus (S. aureus) is considered by the World Health Organization as a high priority pathogen for which new therapies are needed. This is particularly important for biofilm implant-associated infections once the only available treatment option implies a surgical procedure combined with antibiotic therapy. Consequently, these infections represent an economic burden for Healthcare Systems. A new strategy has emerged to tackle this problem: for small bugs, small particles. Here, we describe how nanotechnology-based systems have been studied to treat S. aureus biofilms. Their features, drawbacks and potentialities to impact the treatment of these infections are highlighted. Furthermore, we also outline biofilm models and assays required for preclinical validation of those nanosystems to smooth the process of clinical translation.

Keywords: antibacterial activity; biofilm eradication; drug delivery; nanomedicine; nanotechnology.

Figure 1.

The development of a biofilm involves three main phases: initial attachment, maturation and final detachment. The initial attachment is mediated by host matrix proteins that cover the implant surface immediately after its insertion (Otto 2008). Thus, microbial surface components are able to recognize and bind to these matrix proteins, enabling bacterial colonization. Subsequently, the biofilm grows until it reaches a phase of maturation, adopting a 3D appearance, mainly due to intercellular aggregation mediated by adhesive proteins and exopolymers. Finally, detachment of single cells or cell clusters from the biofilm structure occurs, allowing dissemination and colonization of other sites of the host (Otto 2008).

Figure 2.

Medical devices associated to biofilm infections and the most prevalent bacterial species for each device (Nafee ; Srivastava and Bhargava 2016). A. baumannii, Acinetobacter baumannii; C. meningosepticum, Chryseobacterium meningosepticum; K. ornithinolytica, Klebsiella ornithinolytica; K. pneumoniae, Klebsiella pneumoniae; M. fortuitum, Mycobacterium fortuitum; P. aeruginosa, Pseudomonas aeruginosa; P. mirabilis, Proteus mirabilis; S. aureus, Staphylococcus aureus; S. epidermidis, Staphylococcus epidermidis; S. marcescens, Serratia marcescens. Figure adapted with the permission of Servier Laboratories.

Figure 3.

Schematic representation of in vitro biofilm models and the most common assays performed to evaluate the efficiency of antimicrobial agents against bacterial biofilms (Chen et al. ; Siala et al. 2016). AFM, atomic force microscopy; MBC, minimum bactericidal concentration; MBEC, minimum biofilm eradication concentration; MBIC, minimum biofilm inhibitory concentration; MIC, minimum inhibitory concentration; SEM, scanning electron microscopy. Microscopic images were reprinted with permission from Siala et al. (left) and Chen et al. , American Chemical Society (right).

Figure 4.

Schematic representation of ex vivo and in vivo biofilm models and respective examples of assays to evaluate the efficiency of antimicrobial agents against bacterial biofilms (Siala et al. ; Fang et al. 2017). C. elegans, Caenorhabditis elegans; FESEM, field emission scanning electron microscopy; G. mellonela, Galleria mellonela. Images from experimental assays were reprinted with permission from Siala et al. (left) and Fang et al. (right).