Exploiting cooperative pathogen behaviour for enhanced antibiotic potency: A Trojan horse approach.

Antimicrobial resistance poses an escalating global threat, rendering traditional drug development approaches increasingly ineffective. Thus, novel alternatives to antibiotic-based therapies are needed. Exploiting pathogen cooperation as a strategy for combating resistant infections has been proposed but lacks experimental validation. Empirical findings demonstrate the successful invasion of cooperating populations by non-cooperating cheats, effectively reducing virulence in vitro and in vivo. The idea of harnessing cooperative behaviours for therapeutic benefit involves exploitation of the invasive capabilities of cheats to drive medically beneficial traits into infecting populations of cells. In this study, we employed Pseudomonas aeruginosa quorum sensing cheats to drive antibiotic sensitivity into both in vitro and in vivo resistant populations. We demonstrated the successful invasion of cheats, followed by increased antibiotic effectiveness against cheat-invaded populations, thereby establishing an experimental proof of principle for the potential application of the Trojan strategy in fighting resistant infections.

Towards improved biofilm models.

Biofilms are complex microbial communities that have a critical function in many natural ecosystems, industrial settings as well as in recurrent and chronic infections. Biofilms are highly heterogeneous and dynamic assemblages that display complex responses to varying environmental factors, and those properties present substantial challenges for their study and control. In recent years, there has been a growing interest in developing improved biofilm models to offer more precise and comprehensive representations of these intricate systems. However, an objective assessment for ascertaining the ability of biofilms in model systems to recapitulate those in natural environments has been lacking. In this Perspective, we focus on medical biofilms to delve into the current state-of-the-art in biofilm modelling, emphasizing the advantages and limitations of different approaches and addressing the key challenges and opportunities for future research. We outline a framework for quantitatively assessing model accuracy. Ultimately, this Perspective aims to provide a comprehensive and critical overview of medically focused biofilm models, with the intent of inspiring future research aimed at enhancing the biological relevance of biofilm models.