Synergistic Inhibitory Effect of Polymyxin B in Combination with Ceftazidime against Robust Biofilm Formed by Acinetobacter baumannii with Genetic Deficiency in AbaI/AbaR Quorum Sensing.

Carbapenem resistance of Acinetobacter baumannii poses challenges to public health. Biofilm contributes to the persistence of A. baumannii cells. This study was designed to investigate the genetic relationships among carbapenem resistance, polymyxin resistance, multidrug resistance, biofilm formation, and surface-associated motility and evaluate the antibiofilm effect of polymyxin in combination with other antibiotics. A total of 103 clinical A. baumannii strains were used to determine antibiotic susceptibility, biofilm formation capacity, and motility. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting was used to determine the genetic variation among strains. The distribution of 17 genes related to the resistance-nodulation-cell division (RND)-type efflux, autoinducer-receptor (AbaI/AbaR) quorum sensing, oxacillinases (OXA)-23, and insertion sequence of ISAba1 element was investigated. The representative strains were chosen to evaluate the gene transcription and the antibiofilm activity by polymyxin B (PB) in combination with merapenem, levofloxacin, and ceftazidime, respectively. ERIC-PCR-dependent fingerprints were found to be associated with carbapenem resistance and multidrug resistance. The presence of blaOXA-23 was found to correlate with genes involved in ISAba1 insertion, AbaI/AbaR quorum sensing, and AdeABC efflux. Carbapenem resistance was observed to be negatively correlated with biofilm formation and positively correlated with motility. PB in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with deficiency in AbaI/AbaR quorum sensing. Our results not only clarify the genetic correlation among carbapenem resistance, biofilm formation, and pathogenicity in a certain level but also provide a theoretical basis for clinical applications of polymyxin-based combination of antibiotics in antibiofilm therapy. IMPORTANCE Deeper explorations of molecular correlation among antibiotic resistance, biofilm formation, and pathogenicity could provide novel insights that would facilitate the development of therapeutics and prevention against A. baumannii biofilm-related infections. The major finding that polymyxin B in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with genetic deficiency in AbaI/AbaR quorum sensing further provides a theoretical basis for clinical applications of antibiotics in combination with quorum quenching in antibiofilm therapy.

Ag2S nanoparticle-mediated multiple ablations reinvigorates the immune response for enhanced cancer photo-immunotherapy.

Photothermal therapy (PTT) has been widely used in cancer treatment in recent years. However, it is difficult to completely eliminate tumors by single PTT, and the effects of single dose of PTT frequency on the therapeutic outcome of PTT and the multiple PTT-induced immune response in cancer therapy also remain unclear. Here, water-soluble Ag2S nanoparticles (NPs) with optimal particle size (~15 nm) were synthesized and used as the PTT agents. The in vitro and in vivo results demonstrated that Ag2S NPs had good photothermal conversion in response to the irradiation of an 808 nm laser, and the results indicated that the NPs have potential as contrast agents for photoacoustic imaging as well as good biocompatibility. The in vivo results further revealed that the frequency of the Ag2S NP-mediated PTT affected the cancer therapeutic outcome. The increase of frequency efficiently reduced the primary tumor recurrence and alleviated metastasis. The present study suggested that the mechanism involves multiple PTT cycles inhibiting the proliferation of primary tumor cells and stimulating the systematic immune response in the mouse breast cancer model. Therefore, frequency optimization in photothermal ablation may provide a promising strategy to enhance the therapeutic outcome in cancer therapy.

A brief history of artemisinin: Modes of action and mechanisms of resistance.

The cornerstone of antimalarial treatment, artemisinin, has reduced malaria associated morbidity and mortality worldwide. However, Plasmodium falciparum parasites with reduced sensitivity to artemisinin have emerged, and this threatens malaria control and elimination efforts. In this minireview, we describe the initial development of artemisinin as an antimalarial drug, its use both historically and currently, and our current understanding of its mode of action and the mechanisms by which malaria parasites achieve resistance.

Effects of probiotic fermentation on the enhancement of biological and pharmacological activities of Codonopsis lanceolata extracted by high pressure treatment.

This study was designed to evaluate the enhancement of antioxidant, antimicrobial, enzymatic, cytotoxic, and cognitive activities of Codonopsis lanceolata extracted by high pressure treatment followed by probiotic fermentation. Dried C. lanceolata samples were subjected to 400 MPa for 20 min and then fermented with Bifidobacterium longum B6 (HPE-BLF) and Lactobacillus rhamnosus (HPE-LRF) at 37 °C for 7 days. Compared to conventional extraction (CE-NF, 6.69 mg GAE/g), the phenol amounts of HPE-BLF and HPE-LRF were significantly increased to more than 8 mg GAE/g, while the lowest flavonoid contents were observed for HPE-BLF (0.44 mg RE/mL) and HPE-LRF (0.45 mg RE/mL) (p<0.05). Cinnamic acid was the most abundant phenolic acid in the fermented C. lanceolata. The highest DPPH scavenging activities were observed for HPE-BLF and HPE-LRF, with minimum EC(50) values of 1.26 and 1.18 mg/mL, respectively. The HPE-BLF and HPE-LRF samples exhibited the most noticeable antimicrobial activities against Staphylococcus aureus, Listeria monocytogenes, Salmonella Typhimurium, and Shigella boydii (MICs<15 mg/mL). The fermented C. lanceolata samples effectively inhibited α-glucosidase and tyrosinase activities and potentially improved a scopolamine-induced memory deficit in mice. The application of a fermentation process can effectively improve the biological and pharmacological activities of high-pressure-extracted C. lanceolata by increasing the extraction efficacy and inducing probiotic conversion. The results suggest that the combined treatment of HPE and a fermentation process could be used as alternative extraction method over CE.

Enhancement of antimicrobial and antimutagenic activities of Korean barberry (Berberis koreana Palib.) by the combined process of high-pressure extraction with probiotic fermentation.

BACKGROUND: To evaluate the combined effects of high pressure extraction (HPE) and probiotic fermentation on the antimicrobial and antimutagenic activities, Berberis koreana was subjected to 500 MPa for 30 min and then fermented with Bifidobacterium longum B6 (HPE-BLF) and Lactobacillus paracasei (HPE-LPF) at 37 °C for 6 days. RESULTS: The phenol content was significantly increased to 228 mg GAE g(-1) by the HPE compared to the conventional extraction (CE, 188 mg GAE g(-1)). The HPE-BLF and HPE-LPF showed the highest antimicrobial activity (MIC < 4 mg mL(-1)) against ß-lactam antibiotic sensitive and resistant Staphylococcus aureus. No significant mutagenic effect was observed for CE, HPE, HPE-BLF, and HPE-LPF extracts. The highest antimutagenic activities against frame-shift mutant Salmonella typhimurium were observed at the HPE-LPF (82%), followed by the HPE-BLF (77%). CONCLUSION: The combined HPE and fermentation process could be used as an alternative extraction method for improving the extraction efficacy of medicinal plants. The results will provide pharmaceutically useful information and potential direction for finding new drug sources from medicinal plants.