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Cationic Lignin-Based Hyperbranched Polymers to Circumvent Drug Resistance in Pseudomonas Keratitis
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2021-08-20 , DOI: 10.1021/acsbiomaterials.1c00856
Pei Lin Chee 1 , Cally Owh 1 , Mayandi Venkatesh 2 , Mercy Halleluyah Periayah 2 , Zheng Zhang 1 , Pek Yin Michelle Yew 1 , Huajun Ruan 3 , Rajamani Lakshminarayanan 2, 4, 5 , Dan Kai 1 , Xian Jun Loh 1
Affiliation  

The rise of antimicrobial-resistant bacteria strains has been a global public health concern due to their ability to cause increased patient morbidity and a greater burden on the healthcare system. As one of the potential solutions to overcome such bacterial infections, hyperbranched copolymers with cationic charges were developed. These copolymers were assessed for their antimicrobial efficacy and their bactericidal mechanisms. They were found to be potent against mobile colistin-resistant 1 strains, which was significant as colistin is known to be the last-resort antibiotic against Gram-negative bacteria. Furthermore, there was no sign of mutational resistance developed by E. ColiATCC 25922 and MCR 1+E. Coli against the copolymer even up to 20 passages. The ability to evade inducing resistance would provide invaluable insights for future antibiotic development. Our studies suggest that the bactericidal efficacy comes from the ability to target the outer membrane efficaciously. In vivo study using a Pseudomonas keratitis model showed that the copolymer was compatible with the eye and further supported that the copolymer treatment was effective for complete bacteria elimination.

中文翻译:

基于阳离子木质素的超支化聚合物规避假单胞菌性角膜炎的耐药性

抗菌素耐药菌株的增加已成为全球公共卫生问题,因为它们能够导致患者发病率增加和医疗保健系统负担加重。作为克服此类细菌感染的潜在解决方案之一,开发了具有阳离子电荷的超支化共聚物。评估了这些共聚物的抗微生物功效和杀菌机制。他们被发现对可移动的粘菌素耐药 1 菌株有效,这很重要,因为粘菌素是对抗革兰氏阴性菌的最后一种抗生素。此外,没有迹象表明大肠杆菌ATCC 25922MCR 1+大肠杆菌产生突变抗性对共聚物甚至高达 20 通道。逃避诱导抗性的能力将为未来的抗生素开发提供宝贵的见解。我们的研究表明,杀菌功效来自有效靶向外膜的能力。使用假单胞菌角膜炎模型进行的体内研究表明,该共聚物与眼睛相容,并进一步支持该共聚物处理对于完全消除细菌是有效的。
更新日期:2021-09-13
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