Transcript Profiling of MRSA Biofilms Treated with a Halogenated Phenazine Eradicating Agent: A Platform for Defining Cellular Targets and Pathways Critical to Biofilm Survival

Angewandte Chemie
Yasmeen AbouelhassanRobert W Huigens

Abstract

Bacterial biofilms are surface-attached communities of non-replicating bacteria innately tolerant to antibiotics. Biofilms display differential gene expression profiles and physiologies as compared to their planktonic counterparts; however, their biology remains largely unknown. In this study, we used a halogenated phenazine (HP) biofilm eradicator in transcript profiling experiments (RNA-seq) to define cellular targets and pathways critical to biofilm viability. 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 in 1 hour. Serine proteases and oligopeptide transporters were also found to be up-regulated, whereas glycolysis, arginine deiminase, and urease gene clusters were down-regulated. KEGG analysis revealed that HP-14 impacts metabolic and ABC transporter functional pathways. These findings suggest that MRSA biofilm viability relies on iron homeostasis.

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Citations

Apr 25, 2019·Chemistry, an Asian Journal·Satoru Hiroto
Jul 2, 2020·Natural Product Reports·Roberta J MelanderChristian Melander
Feb 28, 2019·Chembiochem : a European Journal of Chemical Biology·Robert W HuigensHongfen Yang
Nov 24, 2020·Future Medicinal Chemistry·Robert W Huigens
Jan 8, 2021·Frontiers in Microbiology·Priscila Dauros-SingorenkoSimon Swift
Jul 22, 2021·Organic & Biomolecular Chemistry·Robert W Huigens IiiShouguang Jin
Aug 30, 2020·Bioorganic & Medicinal Chemistry Letters·Tao XiaoRobert W Huigens
Apr 6, 2019·Journal of Medicinal Chemistry·Yasmeen AbouelhassanRobert W Huigens

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