Journal
MICROORGANISMS
Volume 9, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms9030485
Keywords
Pseudomonas aeruginosa; two-component system; BfmRS; regulon; biofilm formation
Categories
Funding
- National Natural Science Foundation (NSFC) [31870127, 81861138047]
- Ministry of Science and Technology (MOST) of China [2016YFA0501503, 2019ZX09721001-004-003]
- Science and Technology Commission of Shanghai Municipality [19JC1416400]
- State Key Laboratory of Drug Research [SIMM2003ZZ-03]
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This study investigated the mechanisms of action of BfmR in Pseudomonas aeruginosa, identifying 172 potential target genes and revealing connections between BfmR and the CzcRS and PhoBR two-component systems. Additionally, the results demonstrated the important role of phoB in BfmR-mediated promotion of biofilm formation.
BfmR is a response regulator that modulates diverse pathogenic phenotypes and induces an acute-to-chronic virulence switch in Pseudomonas aeruginosa, an important human pathogen causing serious nosocomial infections. However, the mechanisms of action of BfmR remain largely unknown. Here, using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), we showed that 174 chromosomal regions of P. aeruginosa MPAO1 genome were highly enriched by coimmunoprecipitation with a C-terminal Flag-tagged BfmR. Integration of these data with global transcriptome analyses revealed that 172 genes in 106 predicted transcription units are potential targets for BfmR. We determined that BfmR binds to and modulates the promoter activity of genes encoding transcriptional regulators CzcR, ExsA, and PhoB. Intriguingly, BfmR bound to the promoters of a number of genes belong to either CzcR or PhoB regulon, or both, indicating that CzcRS and PhoBR two-component systems (TCSs) deeply feed into the BfmR-mediated regulatory network. In addition, we demonstrated that phoB is required for BfmR to promote the biofilm formation by P. aeruginosa. These results delineate the direct BfmR regulon and exemplify the complexity of BfmR-mediated regulation of cellular functions in P. aeruginosa.
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