The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial agents.Using bacteriophage-derived lytic enzym...The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial agents.Using bacteriophage-derived lytic enzymes in antibacterial therapy shows promise;however,a thorough comparison and evaluation of their bactericidal efficacy are lacking.This study aimed to compare and investigate the bactericidal activity and spectrum of such lytic enzymes,with the goal of harnessing them for antibacterial therapy.First,we examined the bactericidal activity of spanins,endolysins,and holins derived from 2 Escherichia coli model phages,T1 and T7.Among these,T1-spanin exhibited the highest bactericidal activity against E.coli.Subsequently,we expressed T1-spanin within bacterial cells and assessed its bactericidal activity.T1-spanin showed potent bactericidal activity against all clinical isolates tested,including bacterial strains of 111 E.coli,2 Acinetobacter spp.,3 Klebsiella spp.,and 3 Pseudomonas aeruginosa.In contrast,T1 phage-derived endolysin showed bactericidal activity against E.coli and P.aeruginosa,yet its efficacy against other bacteria was inferior to that of T1-spanin.Finally,we developed a phage-based technology to introduce the T1-spanin gene into target bacteria.The synthesized non-proliferative phage exhibited strong antibacterial activity against the targeted bacteria.The potent bactericidal activity exhibited by spanins,combined with the novel phage synthetic technology,holds promise for the development of innovative antimicrobial agents.展开更多
Phages,including the viruses that lyse bacterial pathogens,offer unique therapeutic advantages,including their capacity to lyse antibiotic-resistant bacteria and disrupt biofilms without harming the host microbiota.Th...Phages,including the viruses that lyse bacterial pathogens,offer unique therapeutic advantages,including their capacity to lyse antibiotic-resistant bacteria and disrupt biofilms without harming the host microbiota.The lack of new effective antibiotics and the growing limitations of existing antibiotics have refocused attention on phage therapy as an option in complex clinical cases such as burn wounds,cystic fibrosis,and pneumonia.This review describes clinical cases and preclinical studies in which phage therapy has been effective in both human and veterinary medicine,and in an agricultural context.In addition,critical challenges,such as the narrow host range of bacteriophages,the possibility of bacterial resistance,and regulatory constraints on the widespread use of phage therapy,are addressed.Future directions include optimizing phage therapy through strategies ranging from phage cocktails to broadening phage host range through genetic modification,and using phages as vaccines or biocontrol agents.In the future,if phage can be efficiently delivered,maintained in a stable state,and phage-antibiotic synergy can be achieved,phage therapy will offer much needed treatment options.However,the successful implementation of phage therapy within the current standards of practice will also require the considerable development of regulatory infrastructure and greater public acceptance.In closing,this review highlights the promise of phage therapy as a critical backup or substitute for antibiotics.It proposes a new role as a significant adjunct to,or even replacement for,antibiotics in treating multidrug-resistant bacterial infections.展开更多
基金supported by the Japan Agency for Medical Research and Development under grant numbers JP23wm0325065,JP22fk0108532,JP21fk0108496,and JP21 wm0325022 to K.K.grant number JP21gm1610002 to L.C.and K.K.JSPS KAKENHI grants numbers 21H02110 and 21K19666 to K.K.
文摘The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial agents.Using bacteriophage-derived lytic enzymes in antibacterial therapy shows promise;however,a thorough comparison and evaluation of their bactericidal efficacy are lacking.This study aimed to compare and investigate the bactericidal activity and spectrum of such lytic enzymes,with the goal of harnessing them for antibacterial therapy.First,we examined the bactericidal activity of spanins,endolysins,and holins derived from 2 Escherichia coli model phages,T1 and T7.Among these,T1-spanin exhibited the highest bactericidal activity against E.coli.Subsequently,we expressed T1-spanin within bacterial cells and assessed its bactericidal activity.T1-spanin showed potent bactericidal activity against all clinical isolates tested,including bacterial strains of 111 E.coli,2 Acinetobacter spp.,3 Klebsiella spp.,and 3 Pseudomonas aeruginosa.In contrast,T1 phage-derived endolysin showed bactericidal activity against E.coli and P.aeruginosa,yet its efficacy against other bacteria was inferior to that of T1-spanin.Finally,we developed a phage-based technology to introduce the T1-spanin gene into target bacteria.The synthesized non-proliferative phage exhibited strong antibacterial activity against the targeted bacteria.The potent bactericidal activity exhibited by spanins,combined with the novel phage synthetic technology,holds promise for the development of innovative antimicrobial agents.
文摘Phages,including the viruses that lyse bacterial pathogens,offer unique therapeutic advantages,including their capacity to lyse antibiotic-resistant bacteria and disrupt biofilms without harming the host microbiota.The lack of new effective antibiotics and the growing limitations of existing antibiotics have refocused attention on phage therapy as an option in complex clinical cases such as burn wounds,cystic fibrosis,and pneumonia.This review describes clinical cases and preclinical studies in which phage therapy has been effective in both human and veterinary medicine,and in an agricultural context.In addition,critical challenges,such as the narrow host range of bacteriophages,the possibility of bacterial resistance,and regulatory constraints on the widespread use of phage therapy,are addressed.Future directions include optimizing phage therapy through strategies ranging from phage cocktails to broadening phage host range through genetic modification,and using phages as vaccines or biocontrol agents.In the future,if phage can be efficiently delivered,maintained in a stable state,and phage-antibiotic synergy can be achieved,phage therapy will offer much needed treatment options.However,the successful implementation of phage therapy within the current standards of practice will also require the considerable development of regulatory infrastructure and greater public acceptance.In closing,this review highlights the promise of phage therapy as a critical backup or substitute for antibiotics.It proposes a new role as a significant adjunct to,or even replacement for,antibiotics in treating multidrug-resistant bacterial infections.
