The flavonoid-sensing regulator AefR is involved in modulating quorum sensing through repressing the MexEF-OprN efflux pump in .

Flavonoids, a major component of plant root exudates, play a crucial role in mediating plant-microbe interactions. However, the mechanisms by which flavonoids are perceived and trigger downstream signaling events in microbes remain largely unknown. In this study, we characterized AefR, a flavonoid-sensing transcriptional regulator from 2P24, a plant growth-promoting rhizobacterium (PGPR) known for its biocontrol properties.

The Two-Component System RstA/RstB Regulates Expression of Multiple Efflux Pumps and Influences Anaerobic Nitrate Respiration in Pseudomonas fluorescens.

Multidrug resistance (MDR) efflux pumps are involved in bacterial intrinsic resistance to multiple antimicrobials. Expression of MDR efflux pumps can be either constitutive or transiently induced by various environmental signals, which are typically perceived by bacterial two-component systems (TCSs) and relayed to the bacterial nucleoid, where gene expression is modulated for niche adaptation. Here, we demonstrate that RstA/RstB, a TCS previously shown to control acid-induced and biofilm-related genes in Escherichia coli, confers resistance to multiple antibiotics in Pseudomonas fluorescens by directly regulating the MDR efflux pumps EmhABC and MexCD-OprJ.

Discovery of pentapeptide-inhibitor hits targeting FKBP51 by combining computational modeling and X-ray crystallography.

FKBP51 is well-known as a cochaperone of Hsp90 machinery and implicated in many human diseases including stress-related diseases, tau-mediated neurodegeneration and cancers, which makes FKBP51 an attractive drug target for the therapy of FKBP51-associated diseases. However, it has been reported that only nature product rapamycin, cyclosporine A, FK506 and its derivatives exhibit good binding affinities when bound to FKBP51 by now. Given the advantages of peptide-inhibitors, we designed and obtained 20 peptide-inhibitor hits through structure-based drug design.

EmhR is an indole-sensing transcriptional regulator responsible for the indole-induced antibiotic tolerance in Pseudomonas fluorescens.

Indole is well known as an interspecies signalling molecule to modulate bacterial physiology; however, it is not clear how the indole signal is perceived and responded to by plant growth promoting rhizobacteria (PGPR) in the rhizosphere. Here, we demonstrated that indole enhanced the antibiotic tolerance of Pseudomonas fluorescens 2P24, a PGPR well known for its biocontrol capacity. Proteomic analysis revealed that indole influenced the expression of multiple genes including the emhABC operon encoding a major multidrug efflux pump.

Discovery and structural analysis of a phloretin hydrolase from the opportunistic human pathogen Mycobacterium abscessus.

The family of PhlG proteins catalyses the hydrolysis of carbon-carbon bonds and is widely distributed across diverse bacterial species. Two members of the PhlG family have been separately identified as 2,4-diacetylphloroglucinol (2,4-DAPG) hydrolase and phloretin hydrolase; however, the extent of functional divergence and catalytic substrates for most members of this family is still unknown. Here, using sequence similarity network and gene co-occurrence analysis, we categorized PhlG proteins into several subgroups and inferred that PhlG proteins from Mycobacterium abscessus (MaPhlG) are likely to be functionally equivalent to phloretin hydrolase.

The antitoxin MqsA homologue in Pseudomonas fluorescens 2P24 has a rewired regulatory circuit through evolution.

The mqsRA operon encodes a toxin-antitoxin pair that was characterized to participate in biofilm and persister cell formation in Escherichia coli. Notably, the antitoxin MqsA possesses a C-terminal DNA-binding domain that recognizes the [5'-AACCT(N) AGGTT-3'] motif and acts as a transcriptional regulator controlling multiple genes including the general stress response regulator RpoS. However, it is unknown how the transcriptional circuits of MqsA homologues have changed in bacteria over evolutionary time.

Transcriptional Regulator PhlH Modulates 2,4-Diacetylphloroglucinol Biosynthesis in Response to the Biosynthetic Intermediate and End Product.

Certain strains of biocontrol bacterium produce the secondary metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) to antagonize soilborne phytopathogens in the rhizosphere. The gene cluster responsible for the biosynthesis of 2,4-DAPG is named and it is still unclear how the pathway-specific regulator within this gene cluster regulates the metabolism of 2,4-DAPG. Here, we found that PhlH in strain 2P24 represses the expression of the gene encoding the 2,4-DAPG hydrolase by binding to a sequence motif overlapping with the -35 site recognized by σ factors.

The environmental endocrine disruptor p-nitrophenol interacts with FKBP51, a positive regulator of androgen receptor and inhibits androgen receptor signaling in human cells.

The compound p-nitrophenol, which shows the anti-androgenic activity, can easily become anthropogenic pollutants and pose a threat to the environment and human health. Previous work indicates that the anti-androgenic mechanism of p-nitrophenol is complex and may involve several components in the AR signaling pathway, but the molecular details of how p-nitrophenol inhibits AR signaling are still not quite clear. Here, we characterized p-nitrophenol binds to the FK1 domain of an AR positive regulator FKBP51 with micromolar affinity and structural analysis of FK1 domain in complex with p-nitrophenol revealed that p-nitrophenol occupies a hydrophobic FK1 pocket that is vital for AR activity enhancement.