Tachyplesin I is a 17-amino-acid cationic antimicrobial peptide (AMP) with a typical cyclic antiparallel ␤-sheet structure that is a promising therapeutic for infections, tumors, and viruses. To date, no bacterial resistance to tachyplesin I has been reported. To explore the safety of tachyplesin I as an antibacterial drug for wide clinical application, we experimentally induced bacterial resistance to tachyplesin I by using two selection procedures and studied the preliminary resistance mechanisms. Aeromonas hydrophila XS91-4-1, Pseudomonas aeruginosa CGMCC1.2620, and Escherichia coli ATCC 25922 and F41 showed resistance to tachyplesin I under long-term selection pressure with continuously increasing concentrations of tachyplesin I. In addition, P. aeruginosa and E. coli exhibited resistance to tachyplesin I under UV mutagenesis selection conditions. Cell growth and colony morphology were slightly different between control strains and strains with induced resistance. Cross-resistance to tachyplesin I and antimicrobial agents (cefoperazone and amikacin) or other AMPs (pexiganan, tachyplesin III, and polyphemusin I) was observed in some resistant mutants. Previous studies showed that extracellular protease-mediated degradation of AMPs induced bacterial resistance to AMPs. Our results indicated that the resistance mechanism of P. aeruginosa was not entirely dependent on extracellular proteolytic degradation of tachyplesin I; however, tachyplesin I could induce increased proteolytic activity in P. aeruginosa. Most importantly, our findings raise serious concerns about the long-term risks associated with the development and clinical use of tachyplesin I.A ntibiotic resistance in pathogenic bacteria and the emergence of superbacteria have attracted attention from health care workers worldwide. Antimicrobial peptides (AMPs) are promising candidates for development of novel alternative antibiotics. However, studies have indicated that some bacteria (especially human pathogens) are resistant to certain AMPs (1, 2), and bacterial resistance to cationic AMPs can arise through long and continual selection in the laboratory (3). Furthermore, some evidence demonstrates that bacteria can evolve resistance to AMPs after extended clinical application (4). Bacterial resistance to the AMPs nisin, pexiganan, and colistin has arisen through their clinical use. There is also evidence that pathogen resistance to AMPs may produce resistance to other AMPs with the same source and similar action mechanisms (5), or even to those with different sources and different action mechanisms (6, 7). Habets and Brockhurst previously reported that therapeutic use of pexiganan, representing a promising new class of AMPs, could drive the evolution of pathogens that are resistant to our own immunity peptides (6). Bacterial evolution of AMP resistance would greatly shorten and restrict the use of AMPs, so elucidation of the potential mechanisms of bacterial resistance to AMPs is required to inform the design of more effective drugs and to reduce the in...

Panax notoginseng and its flowers are both well-known traditional Chinese medicinal herbs. To date, antimicrobial and antioxidant activities of flavonoids from P. notoginseng flowers (PNF) remain unclear. In this study, antimicrobial and antioxidant activities of flavonoids from PNF were investigated. The crude flavonoids were purified using a column (25 cm × 1.5 cm) packed with AB-8 macroporous adsorption resin. Compared with ascorbic acid, the purified flavonoids excelled in scavenging activities on 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid, superoxide anion and hydroxyl radicals at 0.2-1.0 mg/mL concentration. However, flavonoids exhibited weaker reducing power than ascorbic acid at 20-100 μg/mL concentration. In addition, the flavonoids exhibited obvious inhibitory effects on Staphylococcus aureus, Aeromonas hydrophila and Pseudomonas aeruginosa. These results clearly indicate that flavonoids from PNF are effective in scavenging free radicals and have the potential to be used as antioxidants and antimicrobial agents, and also provide the theoretical data for supporting the use of PNF in food, pharmaceutical and cosmetics industries.

Video abstractPoint your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use:https://youtu.be/5BsNhiQUUDIBackground: Tachyplesin I is a cationic antimicrobial peptide with a typical cyclic antiparallel β-sheet structure. We previously demonstrated that long-term continuous exposure to increased concentration of tachyplesin I can induce resistant Gram-negative bacteria. However, no significant information is available about the resistance mechanism of Pseudomonas aeruginosa (P. aeruginosa) to tachyplesin I. Materials and Methods: In this study, the global gene expression profiling of P. aeruginosa strain PA-99 and P. aeruginosa CGMCC1.2620 (PA1.2620) was conducted using transcriptome sequencing. For this purpose, outer membrane permeability and outer membrane proteins (OMPs) were further analyzed.Results: Transcriptome sequencing detected 672 upregulated and 787 downregulated genes, covering Clusters of Orthologous Groups (COGs) of P. aeruginosa strain PA-99 compared with PA1.2620. Totally, 749 differentially expressed genes (DEGs) were assigned to 98 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and among them, a twocomponent regulatory system, a beta-lactam resistance system, etc. were involved in some known genes resistant to drugs. Additionally, we further attempted to indicate whether the resistance mechanism of P. aeruginosa to tachyplesin I was associated with the changes of outer membrane permeability and OMPs. Conclusion: Our results indicated that P. aeruginosa resistant to tachyplesin I was mainly related to reduced entry of tachyplesin I into the bacterial cell due to overexpression of efflux pump, in addition to a decrease of outer membrane permeability. Our findings were also validated by pathway enrichment analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). This study may provide a promising guidance for understanding the resistance mechanism of P. aeruginosa to tachyplesin I.

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