Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacter...Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again.As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages(such as bacteriophage phi X174 and Pyo bacteriophage complex liquid) entered into phase Ⅲ clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced(i) the pharmacological mechanisms and advantages of antibacterial bacteriophages,(ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and(iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.展开更多
Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found i...Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found in the tail fiber protein or the tail spike protein,is reported to have antibiofilm activity.In this study,phage P560isolated from sewage showed specific for capsule locus type KL47 K.pneumoniae,and the enlarged haloes around plaques indicated that P560 encoded a depolymerase.The capsule depolymerase,ORF43,named P560dep,derived from phage P560 was expressed,purified,characterized and evaluated for enzymatic activity as well as specificity.We reported that the capsule depolymerase P560dep,can digest the capsule polysaccharides on the surface of KL47 type K.pneumoniae,and the depolymerization spectrum of P560dep matched to the host range of phage P560,KL47 K.pneumoniae.Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation.Further,a single dose(50μg/mouse)of depolymerase intraperitoneal injection protected 90%–100%of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K.pneumoniae.And pathological changes were alleviated in lung and liver of mice infected by KL47 type K.pneumoniae.It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.展开更多
基金This work was supported by National Key R&D Program of China(No.2021YFA0909900)National Natural Science Foundation of China(Nos.82073777 and 81803442)+3 种基金Liaoning Revitalization Talents Program(No.XLYC180801)Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454)China Postdoctoral Science Foundation(No.2020M680986)General Project of Liaoning Provincial Department of Education(Nos.LJKZ0927 and LJKQZ2021034).
文摘Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again.As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages(such as bacteriophage phi X174 and Pyo bacteriophage complex liquid) entered into phase Ⅲ clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced(i) the pharmacological mechanisms and advantages of antibacterial bacteriophages,(ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and(iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.
基金the National Natural Science Foundation of China(U1803109)the National Key Research and Development Program of China(2018YFC1602500)+6 种基金the National Natural Science Foundation of China(81572032)Major scientific and technological innovation projects in Shandong Province(2019JZZY010719)National Key Research and Development Program(2019YFA0904003)Six Talent Peaks Project in Jiangsu Province(2016-WSN-112)Key research and development project of Jiangsu provincial science and Technology Department(BE2017654)Gusu key health talent of Suzhou,Jiangsu youth medical talents program(QN-867)the Science and Technology Program of Suzhou(SZS201715)。
文摘Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found in the tail fiber protein or the tail spike protein,is reported to have antibiofilm activity.In this study,phage P560isolated from sewage showed specific for capsule locus type KL47 K.pneumoniae,and the enlarged haloes around plaques indicated that P560 encoded a depolymerase.The capsule depolymerase,ORF43,named P560dep,derived from phage P560 was expressed,purified,characterized and evaluated for enzymatic activity as well as specificity.We reported that the capsule depolymerase P560dep,can digest the capsule polysaccharides on the surface of KL47 type K.pneumoniae,and the depolymerization spectrum of P560dep matched to the host range of phage P560,KL47 K.pneumoniae.Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation.Further,a single dose(50μg/mouse)of depolymerase intraperitoneal injection protected 90%–100%of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K.pneumoniae.And pathological changes were alleviated in lung and liver of mice infected by KL47 type K.pneumoniae.It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.
