背景:鲍曼不动杆菌由于其抗生素耐药性而对健康构成威胁。在这里,研究了伊朗鲍曼不动杆菌临床分离株的抗生素敏感性及其与毒素-抗毒素(TA)系统基因的关联。接下来,我们制备了负载美罗培南的壳聚糖纳米颗粒(MP-CS),并研究了它们对美罗培南敏感的细菌分离株的抗菌作用。
方法:在240个临床标本中,评估了60株鲍曼不动杆菌分离株。在调查三种TA系统基因(mazEF,relBE,和higBA)。壳聚糖纳米颗粒在尺寸方面进行了表征,zeta电位,封装效率,和美罗培南释放活性。使用井扩散法评估了它们的抗菌作用,最小抑制浓度(MIC),和菌落形成单位(CFU)计数。通过MTT法测定其细胞毒作用和生物相容性指数,LDH,和ROS形成测定。
结果:氨苄西林,头孢他啶,粘菌素效果最差,阿米卡星和妥布霉素是最有效的抗生素。在60个分离株中,10(16.7%),5(8.3%),45例(75%)是多重耐药(MDR),广泛耐药(XDR),和抗pandrug(PDR),分别。TA体系基因对抗生素耐药性无显著影响。MP-CS纳米颗粒的平均尺寸为191.5,ζ电位为27.3mV,最大包封率为88.32%,释放率为69.57%。MP-CS纳米颗粒介导的类似抗菌作用,与免费美罗培南相比,针对具有显著较低水平的美罗培南的鲍曼不动杆菌分离株。MP-CS纳米颗粒显著地防止了鲍曼不动杆菌分离物的A549和NCI-H292细胞感染,同时表现出良好的生物相容性指数。
结论:应进一步设计和研究负载抗生素的纳米颗粒,以增加其对鲍曼不动杆菌的抗菌作用,并评估其在体内环境中的安全性和适用性。
BACKGROUND: Acinetobacter baumannii is a health threat due to its antibiotic resistance. Herein, antibiotic susceptibility and its association with the Toxin-antitoxin (TA) system genes in A. baumannii clinical isolates from Iran were investigated. Next, we prepared meropenem-loaded chitosan nanoparticles (MP-CS) and investigated their antibacterial effects against meropenem-susceptible bacterial isolates.
METHODS: Out of 240 clinical specimens, 60 A. baumannii isolates were assessed. Antibiotic resistance of the isolates against conventional antibiotics was determined alongside investigating the presence of three TA system genes (mazEF, relBE, and higBA). Chitosan nanoparticles were characterized in terms of size, zeta potential, encapsulation efficiency, and meropenem release activity. Their antibacterial effects were assessed using the well diffusion method, minimum inhibitory concentration (MIC), and colony-forming unit (CFU) counting. Their cytotoxic effects and biocompatibility index were determined via the MTT, LDH, and ROS formation assays.
RESULTS: Ampicillin, ceftazidime, and colistin were the least effective, and amikacin and tobramycin were the most effective antibiotics. Out of the 60 isolates, 10 (16.7%), 5 (8.3%), and 45 (75%) were multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR), respectively. TA system genes had no significant effect on antibiotic resistance. MP-CS nanoparticles demonstrated an average size of 191.5 and zeta potential of 27.3 mV alongside a maximum encapsulation efficiency of 88.32% and release rate of 69.57%. MP-CS nanoparticles mediated similar antibacterial effects, as compared with free meropenem, against the A. baumannii isolates with significantly lower levels of meropenem. MP-CS nanoparticles remarkably prevented A549 and NCI-H292 cell infection by the A. baumannii isolates alongside demonstrating a favorable biocompatibility index.
CONCLUSIONS: Antibiotic-loaded nanoparticles should be further designed and investigated to increase their antibacterial effect against A. baumannii and assess their safety and applicability in vivo settings.