- 作者: Xiaohu Cui, Bing Du, Junxia Feng, Yanling Feng, Zheng Fan, Jinfeng Chen, Jinghua Cui, Lin Gan, Tongtong Fu, Ziyan Tian, Rui Zhang, Chao Yan, Hanqing Zhao, Wenjian Xu, Ziying Xu, Zihui Yu, Zanbo Ding, Zhoufei Li, Yujie Chen, Guanhua Xue & Jing Yuan
- 作者服務機構: 1.Department of Bacteriology, Capital Institute of Pediatrics, Beijing, 100020, China 2.Department of Clinical Laboratory, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China 3.School of Biological Sciences, University of Edinburgh, Edinburgh, UK
- 中文摘要:
- 英文摘要:
Background Klebsiella aerogenes can cause ventilator-associated pneumonia by forming bioflms, and it is frequently
associated with multidrug resistance. Phages are good antibiotic alternatives with unique advantages. There has been
a lack of phage therapeutic explorations, kinetic studies, and interaction mechanism research targeting K. aerogenes.
Methods Plaque assay, transmission electron microscopy and whole-genome sequencing were used to determine
the biology, morphology, and genomic characteristics of the phage. A mouse pneumonia model was constructed
by intratracheal/endobronchial delivery of K. aerogenes to assess the therapeutic efect of phage in vivo. Bioinformatics analysis and a prokaryotic protein expression system were used to predict and identify a novel capsule depolymerase. Confocal laser scanning microscopy, Galleria mellonella larvae infection models and other experiments were
performed to clarify the function of the capsule depolymerase.
Results A novel lytic phage (pK4-26) was isolated from hospital sewage. It was typical of the Podoviridae family and exhibited serotype specifcity, high lytic activity, and high environmental adaptability. The whole genome
is 40,234 bp in length and contains 49 coding domain sequences. Genomic data show that the phage does not carry
antibiotic resistance, virulence, or lysogenic genes. The phage efectively lysed K. aerogenes in vivo, reducing mortality
and alleviating pneumonia without promoting obvious side efects. A novel phage-derived depolymerase was predicted and proven to be able to digest the capsule, remove bioflms, reduce bacterial virulence, and sensitize the bacteria to serum killing.
Conclusions The phage pK4-26 is a good antibiotic alternative and can efectively relieve pneumonia caused
by multidrug-resistant K. aerogenes. It carries a depolymerase that removes bioflms, reduces virulence, and improves
intrinsic immune sensitivity. - 中文關鍵字:
- 英文關鍵字: Klebsiella aerogenes, Pneumonia, Bacteriophage therapy, Depolymerase, Bioflms