Transcript Profiling of MRSA Biofilms Treated with a Halogenated Phenazine Eradicating Agent: A Platform for Defining Cellular Targets and Pathways Critical to Biofilm Survival.
Angew Chem Int Ed Engl. 2018 Sep 19;:
Authors: Abouelhassan Y, Zhang Y, Jin S, Huigens Iii RW
Bacterial biofilms are surface-attached communities of non-replicating bacteria innately tolerant to antibiotics. Biofilms display differential gene expression profiles and physiologies compared to their planktonic counterparts; however, the biology of biofilms remains largely unknown. Here, we used a halogenated phenazine (HP) biofilm eradicator in transcript profiling experiments (RNA-seq) to define cellular targets and pathways critical to biofilm viability. A WoPPER analysis with time course validation (RT-qPCR) revealed that HP-14 induces rapid iron starvation in MRSA biofilms, as evident by the activation of iron-acquisition gene clusters (isd, sir/sbn, hts/sfa, ferrichrome ABC transporters) in 1 hour. Serine proteases and oligopeptide transporters were also found to be up-regulated while glycolysis, arginine deiminase and urease gene clusters were down-regulated. A KEGG analysis revealed that HP-14 impacts metabolic and ABC transporter functional pathways. These findings suggest that MRSA biofilm viability relies on iron homeostasis and establishes a framework to employ next-generation therapeutics to eradicate biofilms.
PMID: 30230671 [PubMed - as supplied by publisher]