A protein may exist as an ensem-ble of di erent conformations in solution,which cannot be repre-sented by a single static structure.Molecular dy-namics(MD)simulation has become a useful tool for sampling protein confo...A protein may exist as an ensem-ble of di erent conformations in solution,which cannot be repre-sented by a single static structure.Molecular dy-namics(MD)simulation has become a useful tool for sampling protein conformations in solution,but force elds and water models are important issues.This work presents a case study of the bacteriophage T4 lysozyme(T4L).We have found that MD simulations using a classic AMBER99SB force eld and TIP4P water model cannot well describe hinge-bending domain motion of the wild-type T4L at the timescale of one microsecond.Other combinations,such as a residue-speci c force eld called RSFF2+and a dispersion-corrected water model TIP4P-D,are able to sample reasonable solution conformations of T4L,which are in good agreement with experimental data.This primary study may provide candidates of force elds and water models for further investigating conformational transition of T4L.展开更多
1 Introduction Viruses are the most abundant biological entities on Earth.They can influence the succession of individual microbial populations,biogeochemical cycles of C/N and,ultimately,microbial community structure...1 Introduction Viruses are the most abundant biological entities on Earth.They can influence the succession of individual microbial populations,biogeochemical cycles of C/N and,ultimately,microbial community structure through killing展开更多
Pathogenic Escherichia coli cause chicken colibacillosis, which is economically devastating to the poultry in- dustry worldwide （Bagheri et al., 2014）. Owing to in- creasing antibiotic resistance, phage therapy reag...Pathogenic Escherichia coli cause chicken colibacillosis, which is economically devastating to the poultry in- dustry worldwide （Bagheri et al., 2014）. Owing to in- creasing antibiotic resistance, phage therapy reagents have been developed to treat bacterial infections （Xu et al., 2015）.展开更多
The increasing emergence of multi-drug resistant Escherichia coli(E.coli)has become a global concern,primarily due to the limitation of antimicrobial treatment options.Phage therapy has been considered as a promising ...The increasing emergence of multi-drug resistant Escherichia coli(E.coli)has become a global concern,primarily due to the limitation of antimicrobial treatment options.Phage therapy has been considered as a promising alternative for treating infections caused by multi-drug resistant E.coli.However,the application of phages as a promising antimicrobial agent is limited by their narrow host range and specificity.In this research,a recombinant T4-like phage,named WGqlae,has been obtained by changing the receptor specificity determinant region of gene 37,using a homologous recombination platform of T4-like phages established by our laboratory previously.The engineered phage WGqlae can lyse four additional hosts,comparing to its parental phages WG01 and QL01.WGqlae showed similar characteristics,including thermo and pH stability,optimal multiplicity of infection and one-step growth curve,to the donor phage QL01.In addition,sequencing results showed that gene 37 of recombinant phage WGqlae had genetically stable even after 20 generations.In planktonic test,phage WGqlae had significant antimicrobial effects on E.coli DE192 and DE205 B.The optical density at 600 nm(OD600)of E.coli in phage WGqlae treating group was significantly lower than that of the control group(P\0.01).Besides,phage WGqlae demonstrated an obvious inhibitory effect on the biofilm formation and the clearance of mature biofilms.Our study suggested that engineered phages may be promising candidates for future phage therapy applications against pathogenic E.coli in planktonic and biofilm forms.展开更多
基金This work was supported by the National Natu-ral Science Foundation of China(No.91953101 and No.21573205)the Strategic Priority Research Program of the Chinese Academy of Science(XDB37040202),the Hefei National Science Center Pilot Project Funds,and the New Concept Medical Research Fund of USTC.
文摘A protein may exist as an ensem-ble of di erent conformations in solution,which cannot be repre-sented by a single static structure.Molecular dy-namics(MD)simulation has become a useful tool for sampling protein conformations in solution,but force elds and water models are important issues.This work presents a case study of the bacteriophage T4 lysozyme(T4L).We have found that MD simulations using a classic AMBER99SB force eld and TIP4P water model cannot well describe hinge-bending domain motion of the wild-type T4L at the timescale of one microsecond.Other combinations,such as a residue-speci c force eld called RSFF2+and a dispersion-corrected water model TIP4P-D,are able to sample reasonable solution conformations of T4L,which are in good agreement with experimental data.This primary study may provide candidates of force elds and water models for further investigating conformational transition of T4L.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41002123 & 41030211)the National Basic Research Program of China (Grant No. 2011CB808800)+1 种基金State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences (No. GBL11201)the Fundamental Research Funds for National University, China University of Geosciences (Wuhan)
文摘1 Introduction Viruses are the most abundant biological entities on Earth.They can influence the succession of individual microbial populations,biogeochemical cycles of C/N and,ultimately,microbial community structure through killing
基金supported by grants from the Nature Science Foundation of Shandong Province of China (grant nos.ZR2013CQ024 and ZR2015CM020)
文摘Pathogenic Escherichia coli cause chicken colibacillosis, which is economically devastating to the poultry in- dustry worldwide （Bagheri et al., 2014）. Owing to in- creasing antibiotic resistance, phage therapy reagents have been developed to treat bacterial infections （Xu et al., 2015）.
基金supported by Grants from the National Natural Science Foundation of China(U1803109)Key research and development plan of Jiangsu province(BE2019304)+2 种基金National Key R&D Program of China(2018YFC1602500)the Central University Basic Scientific Research Fund-Animal pathogenic bacteria(KYZ201846)Jiangsu modern agriculture(waterfowl)industrial technology system disease prevention and control innovation team(JATS[2018]222)
文摘The increasing emergence of multi-drug resistant Escherichia coli(E.coli)has become a global concern,primarily due to the limitation of antimicrobial treatment options.Phage therapy has been considered as a promising alternative for treating infections caused by multi-drug resistant E.coli.However,the application of phages as a promising antimicrobial agent is limited by their narrow host range and specificity.In this research,a recombinant T4-like phage,named WGqlae,has been obtained by changing the receptor specificity determinant region of gene 37,using a homologous recombination platform of T4-like phages established by our laboratory previously.The engineered phage WGqlae can lyse four additional hosts,comparing to its parental phages WG01 and QL01.WGqlae showed similar characteristics,including thermo and pH stability,optimal multiplicity of infection and one-step growth curve,to the donor phage QL01.In addition,sequencing results showed that gene 37 of recombinant phage WGqlae had genetically stable even after 20 generations.In planktonic test,phage WGqlae had significant antimicrobial effects on E.coli DE192 and DE205 B.The optical density at 600 nm(OD600)of E.coli in phage WGqlae treating group was significantly lower than that of the control group(P\0.01).Besides,phage WGqlae demonstrated an obvious inhibitory effect on the biofilm formation and the clearance of mature biofilms.Our study suggested that engineered phages may be promising candidates for future phage therapy applications against pathogenic E.coli in planktonic and biofilm forms.
