Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Effects of precipitation change and nitrogen addition on the composition, diversity, and molecular ecological network of soil bacterial communities in a desert steppe.

Currently, the impact of changes in precipitation and increased nitrogen(N) deposition on ecosystems has become a global problem. In this study, we conducted a 8-year field experiment to evaluate the effects of interaction between N deposition and precipitation change on soil bacterial communities in a desert steppe using high-throughput sequencing technology. The results revealed that soil bacterial communities were sensitive to precipitation addition but were highly tolerant to precipitation reduction. Reduced precipitation enhanced the competitive interactions of soil bacteria and made the ecological network more stable. Nitrogen addition weakened the effect of water addition in terms of soil bacterial diversity and community stability, and did not have an interactive influence. Moreover, decreased precipitation and increased N deposition did not have a superimposed effect on soil bacterial communities in the desert steppe. Soil pH, moisture content, and NH4+-N and total carbon were significantly related to the structure of bacterial communities in the desert steppe. Based on network analysis and relative abundance, we identified Actinobacteria, Proteobacteria, Acidobacteria and Cyanobacteria members as the most important keystone bacteria that responded to precipitation changes and N deposition in the soil of the desert steppe. In summary, we comprehensively analyzed the responses of the soil bacterial community to precipitation changes and N deposition in a desert steppe, which provides a model for studying the effects of ecological factors on bacterial communities worldwide.