3D Synthetic Soft Tissue as a Novel Anti-Biofilm Assay for Drug Screening

Abstract

Background The decline in drug discovery by pharmaceutical companies has diminished the development of antimicrobial agents in pursuit of more profitable areas such as chronic illnesses. In conjunction with this, there is a growing concern of antimicrobial resistance; in particular, microbes in the resistant form of biofilms, according to the Centers for Disease Control and Prevention (CDC). Biofilm-forming pathogens, such as methicillin-resistant staphylococci, are amongst the strains that pose the greatest threat to the management of disease, and has healthcare providers concerned about the reality of a post-antibiotic era. With novel drug development being a primary solution to antimicrobial resistance, potentially new treatments such as antimicrobial nanoparticles and metal complexes are currently being developed. However, a significant setback in the development process is the questionable comparability of often-used screening methods for in vivo infections. The majority of infections are understood to involve microbes in biofilm formation, whose phenotypes may differ greatly with increased resistance in vivo. Current practices to form biofilms typically include formation in rich media, and have been routinely executed for rapid antimicrobial susceptibility testing. However, the majority of these types of assays do not utilise a highly clinically relevant substratum for biofilm development. Therefore, assays that assess the potency of potential antimicrobial drugs should ideallymimic the in vivo environment of biofilm infections in an assessable in vitro setting. Practical simulation of the in vivo biofilm infection at the early stages of drug development is currently difficult to accomplish as there is a lack of standardised assays for susceptibility testing against biofilms.