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
Bacteriophages are viruses that infect bacteria and can choose any one of the two alternative pathways for infection,i.e.,lysis or lysogeny.Phage lysis is one of the conventional biological processes required to sprea...Bacteriophages are viruses that infect bacteria and can choose any one of the two alternative pathways for infection,i.e.,lysis or lysogeny.Phage lysis is one of the conventional biological processes required to spread infection from one bacterium to another.Our analysis suggests that in the paradigm bacteriophage Mu,six proteins might be involved in host cell lysis.Mu has a broad host range,and Mu-like phages were found in both Gram-negative and Gram-positive bacteria.An analysis of the genomes of Mu and Mu-like phages could be useful in elucidating the lysis mechanism in this group of phages.A detailed review of the various mechanisms of phage lysis and different proteins associated with the process will help researchers understand the phage biology and their life cycle in different bacteria.The recent increase in the number of multidrug-resistant(MDR)strains of bacteria and the usual long-term nature of new drug development has encouraged scientists to look for alternative strategies like phage therapy and the discovery of new lysis mechanisms.Understanding the lysis mechanism in the Mu-like phages could be exploited to develop alternative therapeutics to kill drug-resistant pathogenic bacteria.In this review article,we have analyzed the phage Mu-mediated host lysis system,which is unknown till now,and our analysis indicates a possibility of the existence of a new lysis mechanism operating in Mu.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.
基金Hallym University Research Fund and by Basic Science Research Program through the National Research Foundation of Korea(NRF)Funded by the Ministry of Education(NRF-2020R1C1C1008694&NRF-2020R1I1A3074575).
文摘Bacteriophages are viruses that infect bacteria and can choose any one of the two alternative pathways for infection,i.e.,lysis or lysogeny.Phage lysis is one of the conventional biological processes required to spread infection from one bacterium to another.Our analysis suggests that in the paradigm bacteriophage Mu,six proteins might be involved in host cell lysis.Mu has a broad host range,and Mu-like phages were found in both Gram-negative and Gram-positive bacteria.An analysis of the genomes of Mu and Mu-like phages could be useful in elucidating the lysis mechanism in this group of phages.A detailed review of the various mechanisms of phage lysis and different proteins associated with the process will help researchers understand the phage biology and their life cycle in different bacteria.The recent increase in the number of multidrug-resistant(MDR)strains of bacteria and the usual long-term nature of new drug development has encouraged scientists to look for alternative strategies like phage therapy and the discovery of new lysis mechanisms.Understanding the lysis mechanism in the Mu-like phages could be exploited to develop alternative therapeutics to kill drug-resistant pathogenic bacteria.In this review article,we have analyzed the phage Mu-mediated host lysis system,which is unknown till now,and our analysis indicates a possibility of the existence of a new lysis mechanism operating in Mu.
