Department of Medical Biomaterials Engineering and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Microb Pathog. 2019 Oct;135:103625. doi: 10.1016/j.micpath.2019.103625. Epub 2019 Jul 17.
This study was design to evaluate the physiological properties of bacteriophage-insensitive Klebsiella pneumoniae (BIKP) mutants in association with the antibiotic cross-resistance, β-lactamase activity, and gene expression. Klebsiella pneumoniae ATCC 23357(KP), ciprofloxacin-induced antibiotic-resistant K. pneumoniae ATCC 23357 (KP), and clinically isolated antibiotic-resistant K. pneumoniae 10263 (KP) were used to isolate BIKP mutants against KPB1, PBKP02, PBKP21, PBKP29, PBKP33, and PBKP35. PBKP35-induced mutants, including bacteriophage-insensitive K. pneumoniae ATCC 23357 (BIKP), ciprofloxacin-induced K. pneumoniae ATCC 23357 (BIKP), and clinically isolated antibiotic-resistant K. pneumoniae CCARM 10263 (BIKP). BIKP, BIKP, and BIKP were resistant to Klebsiella bacteriophages, KPB1, PBKP02, PBKP21, PBKP29, and PBKP33. The antibiotic cross-resistance to cefotaxime, cephalothin, chloramphenicol, ciprofloxacin, erythromycin, kanamycin, levofloxacin, and nalidixic acid was observed in BIKP. The relative expression levels of vagC was increased by more than 8-folds in BIKP, corresponding to the increased β-lactamase activity. The aac(6')-Ib-cr was overexpressed in BIKP mutants, responsible for aminoglycoside and quinolone resistance. The phage-resistant mutants decreased the antibiotic susceptibilities in association with β-lactamase activity and antibiotic resistance-related gene expression. The results pointed out the cross-resistance of BIKP mutants to antibiotics, which might be considered when applying for the therapeutic use of bacteriophage.
本研究旨在评估与抗生素交叉耐药性、β-内酰胺酶活性和基因表达相关的噬菌体不敏感肺炎克雷伯菌（BIKP）突变体的生理特性。使用肺炎克雷伯菌 ATCC 23357（KP）、环丙沙星诱导的抗生素耐药肺炎克雷伯菌 ATCC 23357（KP）和临床分离的抗生素耐药肺炎克雷伯菌 10263（KP）来分离针对 KPB1、PBKP02、PBKP21、PBKP29、PBKP33 和 PBKP35 的 BIKP 突变体。PBKP35 诱导的突变体，包括噬菌体不敏感肺炎克雷伯菌 ATCC 23357（BIKP）、环丙沙星诱导的肺炎克雷伯菌 ATCC 23357（BIKP）和临床分离的抗生素耐药肺炎克雷伯菌 CCARM 10263（BIKP）。BIKP、BIKP 和 BIKP 均对肺炎克雷伯菌噬菌体、KPB1、PBKP02、PBKP21、PBKP29 和 PBKP33 具有抗性。BIKP 表现出对头孢噻肟、头孢噻吩、氯霉素、环丙沙星、红霉素、卡那霉素、左氧氟沙星和萘啶酸的抗生素交叉耐药性。BIKP 中 vagC 的相对表达水平增加了 8 倍以上，对应于β-内酰胺酶活性的增加。BIKP 突变体中甲氧西林耐药基因 aac(6')-Ib-cr 过度表达，负责氨基糖苷类和喹诺酮类耐药。噬菌体抗性突变体降低了抗生素敏感性，与β-内酰胺酶活性和抗生素耐药相关基因表达有关。结果表明，BIKP 突变体对抗生素具有交叉耐药性，在应用噬菌体治疗时需要考虑这一点。
