Author Correction: The Reaction of Dimerization by Itself Reduces the Noise Intensity of the Protein Monomer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Exposure to One Antibiotic Leads to Acquisition of Resistance to Another Antibiotic via Quorum Sensing Mechanisms.

The vancomycin-resistant Enterococci (VRE) have progressively become a severe medical problem. Although clinics have started to reduce vancomycin prescription, vancomycin resistance has not been contained. We found that the transfer of vancomycin resistance in Enterococcus faecalis increased more than 30-fold upon treatment by streptomycin. Notably, treatment with an antibiotic caused the bacteria to become resistant to another. The response was even stronger in the well-studied plasmid pCF10 and the number of transconjugants increased about 100,000-fold. We tested four different antibiotics, and all of them induced conjugal response. Through a mathematical model based on gene regulation, we found a plausible explanation. Via quorum sensing, the change of the cell density triggers the conjugation. Moreover, we searched for generality and found a similar strategy in Bacillus subtilis. The outcome of the present study suggests that even common antibiotics must not be overused.

The Reaction of Dimerization by Itself Reduces the Noise Intensity of the Protein Monomer.

Because of the small particle number of intracellular species participating in genetic circuits, stochastic fluctuations are inevitable. This intracellular noise is detrimental to precise regulation. To maintain the proper function of a cell, some natural motifs attenuate the noise at the protein level. In many biological systems, the protein monomer is used as a regulator, but the protein dimer also exists. In the present study, we demonstrated that the dimerization reaction reduces the noise intensity of the protein monomer. Compared with two common noise-buffering motifs, the incoherent feedforward loop (FFL) and negative feedback control, the coefficient of variation (COV) in the case of dimerization was 25% less. Furthermore, we examined a system with direct interaction between proteins and other ligands. Both the incoherent FFL and negative feedback control failed to buffer the noise, but the dimerization was effective. Remarkably, the formation of only one protein dimer was sufficient to cause a 7.5% reduction in the COV.

The Insight into Protein-Ligand Interactions, a Novel Way of Buffering Protein Noise in Gene Expression.

Random fluctuations are often considered detrimental in the context of gene regulation. Studies aimed at discovering the noise-buffering strategies are important. In this study, we demonstrated a novel design of attenuating noise at protein-level. The protein-ligand interaction dramatically reduced noise so that the coefficient of variation (COV) became roughly 1/3. Remarkably, in comparison to the other two noise-buffering methods, the negative feedback control and the incoherent feedforward loop, the COV of the target protein in the case of protein-ligand interaction appeared to be less than 1/2 of that of the other two methods. The high correlation of the target protein and the ligand grants the present method great ability to buffer noise. Further, it buffers noise at the stage after translation so it is also capable of attenuating the noise inherited from the process of translation.

Antischistosomal activity of N,N'-arylurea analogs against Schistosoma japonicum.

Although the antischistosomal activities of N,N'-arylurea analogs were reported, systematic structure-activity relationships have not been conducted. In this Letter, we reported the design, synthesis and evaluation of 45 N,N'-arylurea analogs. Among these prepared compounds, 13 compounds were urea linker modified and 32 were N,N'-arylurea derivatives. The activity evaluation revealed 12 analogs exhibited IC50 values lower than 22.6µM, and 7 of them had IC50 less than 10µM against the juvenile Schistosoma japonicum in vitro. Their worm killing potency was even higher against adult worm. Unfortunately, low to moderate worm burden reduction of 0-33.4% was recorded after administration of a single oral dose of 200mg/kg or 400mg/kg to mice harboring S. japonicum.

Benzofurazan derivatives as antifungal agents against phytopathogenic fungi.

A series of benzofurazan derivatives were prepared and evaluated for their biological activities against four important phytopathogenic fungi, namely, Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, using the mycelium growth inhibition method. The structures of these compounds were characterized by (1)H NMR, (13)C NMR, and HRMS. N-(3-chloro-4-fluorophenyl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (A3) displayed the maximum antifungal activity against R. solani (IC50 = 1.91 µg/mL), which is close to that of the positive control Carbendazim (IC50 = 1.42 µg/mL). For other benzofurazan derivatives with nitro group at R(4) position (A series), 9 out of 30 compounds exhibited high antifungal effect against strain R. solani, with IC50 values less than 5 µg/mL. Most of the derivatives with substituents at R(2) and R(3) positions (B series) displayed moderate growth inhibition against S. sclerotiorum (IC50 < 25 µg/mL). Also, several benzofuran derivatives with nitro group at R(4) position and another conjugated aromatic ring at the R(1) position of the phenyl ring displayed high antifungal capability against strain R. solani. Compounds with substituents at R(2) and R(3) position had moderate efficacy against strain S. sclerotiorum.