Bacteriophages(hence termed phages)are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection.However,the molecular nature of phage i...Bacteriophages(hence termed phages)are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection.However,the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades,limiting their therapeutic application.While many phages and their functional repertoires remain unknown,the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria.Furthermore,the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation.Importantly,the narrow host range,immense antibacterial repertoire,and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic,commensal and pathobiont members of the microbiome,thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiomeassociated diseases.In this review,we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage-bacteria-host interactions may facilitate the development of novel phage-based therapeutics.We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.展开更多
Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality.The underlying mechanism of infections has been widely investigated by scientist,w...Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality.The underlying mechanism of infections has been widely investigated by scientist,while standard wound management is routinely been used in general practice.However,strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization,delayed healing and drug resistance.In the present review,we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis,non-surgical methods and surgical methods.Moreover,we highlight emerging innovations in the development of antimicrobial peptides,phages,controlled drug delivery,wound dressing materials and herbal medicine,and find that sensitive diagnostics,combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.展开更多
AIM: To probe the organizational structure of the adsorption apparatus of bacteriophage epsilon 15(E15) using genetic and biochemical methodology METHODS: Hydroxylamine was used to create nonsense mutants of bacteriop...AIM: To probe the organizational structure of the adsorption apparatus of bacteriophage epsilon 15(E15) using genetic and biochemical methodology METHODS: Hydroxylamine was used to create nonsense mutants of bacteriophage E15. The mutants were then screened for defects in their adsorption apparatus proteins, initially by measuring the concentrations of free tail spike proteins in lysates of cells that had been infected by the phage mutants under nonpermissive growth conditions. Phage strains whose infected cell lysates contained above-average levels of free tail spike protein under non-permissive growth conditions were assumed to contain nonsense mutations in genes coding for adsorption apparatus proteins.These mutants were characterized by classical genetic mapping methods as well as automated sequencing of several of their genes. Finally, sodium dodecyl sulfatepolyacrylamide gel electrophoresis and autoradiography were used to examine the protein compositions of the radioactive particles produced when the various mutants were grown on a non-permissive host cell in the presence of 35S-methionine and co-purified along with E15 wt phage on Cs Cl block gradients.RESULTS: Our results are consistent with gp4 forming the portal ring structure of E15. In addition, they show that proteins gp15 and gp17 likely comprise the central tube portion of the E15 adsorption apparatus, with gp17 being more distally positioned than gp15 and dependent upon both gp15 and gp16 for its attachment. Finally, our data indicates that tail spike proteins comprised of gp20 can assemble onto nascent virions that contain gp7, gp10, gp4 and packaged DNA, but which lack both gp15 and gp17, thereby forming particles that are of sufficient stability to survive Cs Cl buoyant density centrifugation.CONCLUSION: The portal ring(gp4) of E15 is bound to tail spikes(gp20) and the tail tube(gp15 and gp17); gp17's attachment requires both gp15 and gp16.展开更多
Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GMCSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GMCSF genemodified allogenic ...Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GMCSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GMCSF genemodified allogenic macrophages on tumorbearing mice observed. The peritoneal macrophages of C57BL/6 mice were transfected with GMCSF gene mediated by recombinant adenovirus and the subcutaneous CT26 colon adenocarcinomabearing BALB/c mice were treated by intratumoral injection of the above macrophages. The survival time of the tumorbearing mice were prolonged significantly and some tumor mass disappeared completely. The necroses of the tumor cells and massive infiltration of inflammatory cells were observed 6 days after treatment. 30 days after treatment, only the leftover of tumor cells and the inflammatory cells remained. The data indicated that introtumoral injection of GMCSF genemodified allogenic macrophages displayed more potent therapeutic effect on the preestablished tumorbearing mice.展开更多
基金funded by an EMBO Long-term Fellowship ALTF 767-2017.
文摘Bacteriophages(hence termed phages)are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection.However,the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades,limiting their therapeutic application.While many phages and their functional repertoires remain unknown,the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria.Furthermore,the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation.Importantly,the narrow host range,immense antibacterial repertoire,and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic,commensal and pathobiont members of the microbiome,thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiomeassociated diseases.In this review,we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage-bacteria-host interactions may facilitate the development of novel phage-based therapeutics.We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.
基金supported by National Science Foundation of China(82172217)Fundamental Science(Natural Science)Research Project of the Jiangsu Higher Education Institutions of China(No.21KJB360016)Natural Science Foundation of Nanjing University of Chinese Medicine(No.XZR2020069).
文摘Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality.The underlying mechanism of infections has been widely investigated by scientist,while standard wound management is routinely been used in general practice.However,strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization,delayed healing and drug resistance.In the present review,we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis,non-surgical methods and surgical methods.Moreover,we highlight emerging innovations in the development of antimicrobial peptides,phages,controlled drug delivery,wound dressing materials and herbal medicine,and find that sensitive diagnostics,combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.
基金Supported by The NIH-AREA Grant,No.1R15GM52696-01the NSF-RUI Grant,No.DMB-8608480+2 种基金the Howard Hughes Medical Research Institute(two grants to the PLNU Biology Department)Research Associates of PLNU(a 300 member alumni support group)the PLNU Administration
文摘AIM: To probe the organizational structure of the adsorption apparatus of bacteriophage epsilon 15(E15) using genetic and biochemical methodology METHODS: Hydroxylamine was used to create nonsense mutants of bacteriophage E15. The mutants were then screened for defects in their adsorption apparatus proteins, initially by measuring the concentrations of free tail spike proteins in lysates of cells that had been infected by the phage mutants under nonpermissive growth conditions. Phage strains whose infected cell lysates contained above-average levels of free tail spike protein under non-permissive growth conditions were assumed to contain nonsense mutations in genes coding for adsorption apparatus proteins.These mutants were characterized by classical genetic mapping methods as well as automated sequencing of several of their genes. Finally, sodium dodecyl sulfatepolyacrylamide gel electrophoresis and autoradiography were used to examine the protein compositions of the radioactive particles produced when the various mutants were grown on a non-permissive host cell in the presence of 35S-methionine and co-purified along with E15 wt phage on Cs Cl block gradients.RESULTS: Our results are consistent with gp4 forming the portal ring structure of E15. In addition, they show that proteins gp15 and gp17 likely comprise the central tube portion of the E15 adsorption apparatus, with gp17 being more distally positioned than gp15 and dependent upon both gp15 and gp16 for its attachment. Finally, our data indicates that tail spike proteins comprised of gp20 can assemble onto nascent virions that contain gp7, gp10, gp4 and packaged DNA, but which lack both gp15 and gp17, thereby forming particles that are of sufficient stability to survive Cs Cl buoyant density centrifugation.CONCLUSION: The portal ring(gp4) of E15 is bound to tail spikes(gp20) and the tail tube(gp15 and gp17); gp17's attachment requires both gp15 and gp16.
文摘Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GMCSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GMCSF genemodified allogenic macrophages on tumorbearing mice observed. The peritoneal macrophages of C57BL/6 mice were transfected with GMCSF gene mediated by recombinant adenovirus and the subcutaneous CT26 colon adenocarcinomabearing BALB/c mice were treated by intratumoral injection of the above macrophages. The survival time of the tumorbearing mice were prolonged significantly and some tumor mass disappeared completely. The necroses of the tumor cells and massive infiltration of inflammatory cells were observed 6 days after treatment. 30 days after treatment, only the leftover of tumor cells and the inflammatory cells remained. The data indicated that introtumoral injection of GMCSF genemodified allogenic macrophages displayed more potent therapeutic effect on the preestablished tumorbearing mice.
