RESUMO
Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC50 ≥ 11.9 μg·mL-1). Compounds 13 (MIC: 2-4 μg·mL-1) and 15 (MIC: 1-2 μg·mL-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL-1). Compound 13 (HC50: 24.0 ± 4.3 μg·mL-1) displayed noticeably decreased hemolytic activity compared to melittin (HC50: 5.3 ± 0.4 μg·mL-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.
RESUMO
Objective To monitor the clinical distribution of Gram-positive pathogen infection and drug-resistance situation in hospitalized children with lower respiratory tract, and guide rational application of antibiotics. Methods The isolated cultures results and drug sensitivity test result of 1 219 sputum specimens in hospitalized children with lower respiratory tract were studied. Results The 1 249 strains were isolated from 1 219 sputum specimen samples. Among which, Gram-positive pathogen was 318 strains, accounting for 25.46% (318/1 249). In 318 strains Gram-positive pathogens, staphylococcus aureus was 127 strains (39.94% ), streptococcus pneumoniae was 92 strains (28.93% ), staphylococcus epidermidis was 76 strains (23.90%), and enterococcus was 23 strains (7.23%). Then, different strains of pathogens showed totally disparate drug-resistance situations, especially towards penicillin, and the drug resistant rate was highest (89.62% , 285/318), while the drug resistant rates were also high among erythromycin, cefazolin, oxacillin, azithromycin and clindamycin: 66.67% (212/318), 52.52% (167/318), 49.06% (156/318), 49.06% (156/318) and 43.08% (137/318); meanwhile, the isolated Gram-positive pathogens showed no drug-resistance to vancomycin and linezolid. Conclusions Only using antibiotics rationally according to pathogen identification and drug sensitivity test result, can effectively control the pathogen infections.
RESUMO
This study investigated the antimicrobial activity of Enterococcus faecium FAIR-E 198 against Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. Using the critical-dilution method, the bacteriocin produced by E. faecium FAIR-E 198 inhibited all L. monocytogenes strains evaluated (1,600 to 19,200 AU mL-1). However, none of the B. cereus and S. aureus strains investigated were inhibited. The maximum activity of this bacteriocin (800 AU mL-1) was observed in MRS broth, while the activity in milk was 100 AU mL-1. In the co-cultivation test in milk, B. cereus K1-B041 was reduced to below the detection limit (1.00 log CFU mL-1) after 48 h. E. faecium reduced the initial L. monocytogenes Scott A population by 1 log CFU mL-1 after 3 h at 35ºC. However, the pathogen regained growth, reaching 3.68 log CFU mL-1 after 48 h. E. faecium did not influence the growth of S. aureus ATCC 27154 during the 48 h of co-cultivation. Therefore, it can be concluded that the effectiveness of the antimicrobial activity of E. faecium FAIR-E 198 is strictly related to the species and strain of the target microorganism and to the culture medium.