Previous studies have determined that CYP3A and multidrug resistance protein 1 (MDR1) polymorphisms can affect the pharmacokinetics and pharmacodynamics of amlodipine in both healthy subjects and those with early hypertensive renal disease. In the current study, our objective was to analyze the association between the CYP3A4*1G, CYP3A5*3, and MDR1 C3435T gene polymorphisms and the antihypertensive efficacy of amlodipine in hypertensive patients after renal transplantation. Materials: Blood samples were collected from 76 patients on amlodipine therapy (5 mg/d). The CYP3A4*1G, CYP3A5*3, and MDR1 C3435T genetic polymorphisms were detected using both polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing. Subsequently, antihypertensive effects were analyzed according to genotype, and blood pressure values were measured and recorded weekly. Four weeks of treatment with amlodipine was sufficient to successfully control blood pressure in 79% of patients. The efficacy of amlodipine in patients with the CYP3A5*3*3 genotype was significantly higher than that in patients with other CYP3A5 genotypes (p < 0.05). In addition, the reduction in diastolic blood pressure (DBP) in patients with the CYP3A5*3*3 and CYP3A4*1G*1G genotypes was significantly higher than that in patients with other CYP3A5 and CYP3A4 genotypes, respectively (p < 0.05). Furthermore, we found that linkage disequilibrium exists between the CYP3A4 *1G and CYP3A5*3 alleles and observed that the most significant reduction in DBP occurred in patients with the *1/*1 and *3/*3 genotype. Our study demonstrates that amlodipine treatment may effectively control blood pressure (BP) for hypertensive patients following renal transplantation. Additionally, we found that the CYP3A5*3 polymorphism affects the antihypertensive efficacy of amlodipine in Chinese hypertensive patients after renal transplantation. .

Raoultella planticola is an emerging pathogen causing several infections in humans, and its roles in the propagation of antibiotic resistance genes (ARGs) remain uncharacterized. In this study, a carbapenem and tigecycline-resistant R. planticola isolate was recovered from hospital sewage. It carried nine plasmids, bearing 30 ARGs, including one bla_KPC-2 and two bla_NDM-1. It also contained a plasmid-borne efflux pump gene cluster, tmexCD1-toprJ, conferring resistance to tigecycline. Analysis of plasmid sequences revealed that both bla_NDM-1-carrying plasmids were highly similar to those recovered from humans, reinforcing the close relatedness of environmental and clinical isolates. We also identified that plasmid bearing bla_NDM-1 or tmexCD1-toprJ1 was transferable, and can be stabilized in the host bacteria, indicating that the R. planticola isolate has a considerable potential in the dissemination of ARGs. Besides, we found that this isolate could produce biofilm and was virulent in a Galleria mellonella infection model. In conclusion, our study shows the convergence of virulence and multidrug resistance in a R. planticola isolate. This potentially virulent superbug may disseminate into its receiving rivers, and finally to humans through cross-contamination during recreation activities or daily use of water, which poses a risk to public health.

Kitchen waste oil is composed of long chain triglycerides (LCTs) that has high energy density. However, it is hard to be degraded by microbes, thereby leading to increasing levels of environmental pollution due to landfill disposition. In this study, we isolated and characterized a novel bacterium Pseudomonas aeruginosa PA-3 that could convert kitchen waste oil into biofertilizer. PA-3 could survive on trilaurin or kitchen waste oil as the sole carbon source, and 10 g L⁻¹ trilaurin or kitchen waste oil was completely consumed within 7 days. Interestingly, the degradation products of kitchen waste oil can be used as biofertilizer in promoting cabbage growth. The plant height, leaf area and stem diameter of cabbage plants were all increased with the addition of kitchen waste oil cultivation products into the soil. Kitchen waste oil degradation products were analyzed by gas chromatography mass spectrometry (GC-MS), and short chain alcohols or fatty acids were observed to be the main products. To unravel the mechanism underlying the accelerated cabbage growth, bacterial diversity of the soil was investigated after using this biofertilizer. Results showed that agricultural probiotics accumulated with the addition of kitchen waste oil cultivation products. Finally, the whole genome of PA-3 was sequenced and analyzed, which showed the existence of a complete β-oxidation pathway in the genome of PA-3. To our knowledge, this is the first study on kitchen waste oil degradation and re-utilization by bacteria, which provides a new method for waste source re-utilization.

Multidrug resistance poses a major challenge to antibiotic therapy. A principal cause of antibiotic resistance is through active export by efflux pumps embedded in the bacterial membrane. Major facilitator superfamily (MFS) efflux pumps constitute a major group of transporters, which are often related to quinolone resistance in clinical settings. Although a rocker-switch model is proposed for description of their conformational transitions, detailed changes in this process remain poorly understood. Here we used MdfA from E. coli as a representative MFS efflux pump to investigate factors that can affect its conformational transition in silico. Molecular dynamics (MD) simulations of MdfA’s inward and outward conformations revealed an intermediate state between these two conformations. By comparison of the subtle differences between the intermediate state and the average state, we indicated that conformational transition from outward to inward was initiated by protonation of the periplasmic side. Subsequently, hydrophilic interaction of the periplasmic side with water was promoted and the regional structure of helix 1 was altered to favor this process. As the hydrophobic interaction between MdfA and membrane was also increased, energy was concentrated and stored for the opposite transition. In parallel, salt bridges at the cytoplasmic side were altered to lower probabilities to facilitate the entrance of substrate. In summary, we described the total and local changes during MdfA’s conformational transition, providing insights for the development of potential inhibitors.

The value of Agarwood increases with time due to the gradual release of its major components, but the mechanism behind this remains unclear. Herein we reveal that the potential driving force of this process is the degradation of cellulose in Agarwood by its saprophytic Bacillus subtilis. We selected 10-year-old Agarwood from different places and then isolated the saprophytic bacteria. We confirmed these bacteria from different sources are all Bacillus and confirmed they can degrade cellulose, and the highest cellulase activity reached 0.22 U/mL. By co-cultivation of the bacterium and Agarwood powder, we found that three of the strains could release the effective components of Agarwood, while they had little effect in increasing the same components in living Aquilaria sinensis. Finally, we demonstrated that these saprophytic Bacillus subtilis have similar effects on Zanthoxylum bungeanum Maxim and Dalbergiaod orifera T. Chen, but not on Illicium verum Hook. f, Cinnamomum cassia Presl and Phellodendron chinense Schneid. In conclusion, our experiment revealed that the saprophytic Bacillus release the effective components of Agarwood by degrading cellulose, and we provide a promising way to accelerate this process by using this bacterial agent.