Sedaghati Mahsa, Akbari Reza, Lotfollahi Hagghi Lida, Yousefi Saber, Mesbahi Tahere, Delfi Mahdieh
Department of Microbiology and Virology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Front Microbiol. 2024 Nov 21;15:1480299. doi: 10.3389/fmicb.2024.1480299. eCollection 2024.
The emergence of multidrug-resistant bacteria and also biofilm-associated infections is a great health concern due to the failure of available antibiotics. This has alerted scientists to developing alternative antibiotics. Melittin as an antimicrobial peptide has antibacterial synergistic activity in combining with conventional antibiotics against pathogenic bacteria. Accordingly, this study aimed to assess the synergistic effect of melittin in combination with Ciprofloxacin, Rifampicin, and Chloramphenicol against MDR strains of .
Fifty strains of were isolated from clinical specimens. The antibiotic susceptibility of isolates was evaluated by the disk diffusion method. The MIC and MBC of melittin and melittin-antibiotics combination against isolated strains were examined by microdilution method. The probable synergism between melittin and antibiotics was assayed using the FIC protocol. Time-killing kinetics and anti-biofilm effects of melittin and melittin-antibiotics combination were evaluated using time-kill kinetics and crystal violet staining method, respectively. The toxicity of the melittin-antibiotics combination on the HEK293 cell line was also assessed by the MTT assay method.
Out of 50 isolates of , 15 strains are considered to be multidrug strains. Among MDR strains of , 42.85% were resistant to cefepime and ceftazidime and all urine-originate isolates were resistant to cotrimoxazole. A combination of MIC dose of ciprofloxacin and melittin decreased resistance against ciprofloxacin up to 33%. The ciprofloxacin-melittin combination showed a favorable synergism and anti-biofilm effect and was also 30.3% less toxic than melittin alone at 4 μg/ml against the HEK293 cell line. In contrast to ciprofloxacin, with the melittin-rifampicin and melittin-chloramphenicol combinations, an addition effect occurred, respectively, in 86.66 and 53.33% of MDR strains of .
Combining melittin's antibacterial and anti-biofilm properties with traditional antibiotics may offer a novel strategy to address antibiotic resistance in . The simultaneous administration of melittin and ciprofloxacin in a single dose has shown a marked increase in antibacterial effectiveness while minimizing toxicity to the HEK293 cell line. It is advisable to conduct additional research to explore the combined antibacterial effects of melittin and ciprofloxacin in a wider range of clinical samples, animal models, and clinical trial settings.
由于现有抗生素失效，多重耐药菌以及生物膜相关感染的出现成为重大的健康问题。这促使科学家们研发替代抗生素。蜂毒肽作为一种抗菌肽，与传统抗生素联合使用时对病原菌具有抗菌协同活性。因此，本研究旨在评估蜂毒肽与环丙沙星、利福平及氯霉素联合使用对[具体病原菌名称未给出]多重耐药菌株的协同作用。
从临床标本中分离出50株[具体病原菌名称未给出]菌株。采用纸片扩散法评估分离株的抗生素敏感性。通过微量稀释法检测蜂毒肽及蜂毒肽 - 抗生素组合对分离菌株的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）。使用FIC方案测定蜂毒肽与抗生素之间可能的协同作用。分别采用时间杀菌动力学和结晶紫染色法评估蜂毒肽及蜂毒肽 - 抗生素组合的时间杀菌动力学和抗生物膜效果。还通过MTT法评估蜂毒肽 - 抗生素组合对HEK293细胞系的毒性。
在50株[具体病原菌名称未给出]分离株中，15株被认为是多重耐药菌株。在[具体病原菌名称未给出]的多重耐药菌株中，42.85%对头孢吡肟和头孢他啶耐药，所有尿液来源的分离株对复方新诺明耐药。环丙沙星MIC剂量与蜂毒肽联合使用可使对环丙沙星的耐药性降低达33%。环丙沙星 - 蜂毒肽组合显示出良好的协同作用和抗生物膜效果，并且在4μg/ml时对HEK293细胞系的毒性比单独使用蜂毒肽低30.3%。与环丙沙星不同，蜂毒肽 - 利福平组合和蜂毒肽 - 氯霉素组合在分别86.66%和53.33%的[具体病原菌名称未给出]多重耐药菌株中产生相加作用。
将蜂毒肽的抗菌和抗生物膜特性与传统抗生素相结合可能为解决[具体病原菌名称未给出]的抗生素耐药性提供一种新策略。蜂毒肽和环丙沙星单剂量同时给药已显示出抗菌效果显著提高，同时对HEK293细胞系的毒性最小化。建议开展更多研究，以探索蜂毒肽和环丙沙星在更广泛的临床样本、动物模型和临床试验环境中的联合抗菌效果。
