Data from: Mechanisms of antibiofilm compounds JG-1 and M4 across multiple species: Alterations of protein interactions essential to biofilm formation

The majority of human bacterial pathogens have the ability to form
biofilms in vivo on body tissues and implantable medical devices.
Biofilm-mediated chronic bacterial infections are difficult to treat due
to their recalcitrance to antimicrobials and immune effectors, often
requiring invasive surgical intervention to clear the infection. The
difficulty in effectively executing these treatment strategies underscores
the need for therapeutic agents that specifically target the biofilm
state. To this end, we previously identified two small molecules, JG-1 and
M4, that in vitro effectively inhibit and disperse biofilms of Salmonella
Typhimurium and members of the ESKAPE pathogen group, including
Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii.
In addition to its antibiofilm effects, M4 has a bactericidal effect on
Staphylococcus aureus and Enterococcus faecium. While these compounds have
promising utility as antimicrobial agents, their mechanism of action
remains unknown. By employing multiple techniques including RNAseq,
thermal proteome profiling, and site directed mutagenesis, we identified
multiple proteins essential to biofilm formation and evaluated their role
in the presence of JG-1 and M4 in mutant and wildtype backgrounds. We
report that the JG-1 and M4 actions are influenced by proteins important
to biofilm maintenance, including OmpA, OmpC, and TrxA. Compound-bacteria
interactions cause transcriptional changes that result in biofilm
dispersal, and modulation of other virulence mechanisms, including
invasion and motility. Additionally, we report that M4 interacts with S.
aureus CodY, which promotes cell death, while the specific targets in S.
Typhimurium and E. cloacae remain elusive. Collectively, this study
presents an empirical investigation into JG-1 and M4’s mechanism of action
in S. Typhimurium, E. cloacae, and S. aureus, and how the antibiofilm
compounds disrupt microbial community dynamics, ultimately driving biofilm
dispersal or cell death.