Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this review we focused on the antibacterial properties of AF, specifically researching the minimal inhibitory concentrations (MIC) of AF in both mono- and diderm bacteria reported so far in literature. AF proves to be highly effective against monoderm bacteria, while diderm are far less susceptible, probably due to the outer membrane barrier. We also reported the current mechanistic hypotheses concerning the antimicrobial properties of AF, although a conclusive description of its antibacterial mode of action is not yet available. Even if its mechanism of action has not been fully elucidated yet and further studies are required to optimize its delivery strategy, AF deserves additional investigation because of its unique mode of action and high efficacy against a wide range of pathogens, which could lead to potential applications in fighting antimicrobial resistance and improving therapeutic outcomes in infectious diseases.
Bacteria usually possess more than one quorum sensing (QS) regulatory modules that sometimes form complex regulatory networks. These configurations have evolved through the integration of novel transcription factors into the native regulatory systems. However, the selective advantages provided by these alternative configurations on QS-related phenotypes is poorly predictable only based on their underlying network structure. Here, we show that the acquisition of extra regulatory modules of QS has important consequences on the overall regulation of microbial growth by significantly reducing the variability in the final cell density in Burkholderia. By mapping the distribution of horizontally transferred QS modules in extant bacterial genomes, we found that these tend to add up to already-present modules in the majority of cases. We then selected a strain harboring two intertwined QS modules and, using mathematical modeling, we predicted an intrinsic ability of the newly acquired module to buffer the variability in the final cell density. We validated this prediction choosing one strain possessing both systems, deleting one of the two and measuring parameters such as cell density and QS synthase promoter activity. Finally, using transcriptomics, we show that the de-regulation of metabolism likely plays a key role in differentiating the two configurations.