噬菌体裂解酶的应用概况
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摘要
近年来由于耐药菌的频频出现,抗生素在抗感染领域面临前所未有的挑战,目前研制可裂解病原菌的噬菌体制剂已为一大热点。噬菌体裂解酶是双链DNA噬菌体在基因组复制晚期合成的一类蛋白质,它能够水解细菌细胞壁中的肽聚糖从而杀灭细菌。噬菌体裂解酶在体内外的试验中都表现出很高的杀菌性、种属特异性和安全性,因而具有广阔的应用前景。简要介绍了噬菌体裂解酶的结构性质,并对裂解酶显示出的抗菌性能及应用进行了综述。
More recently, the original application of phage as therapeutics to treat human and animal infections has been rekindled, particularly in an era where antibiotic resistance has become so problematic. Bacteriophage lysins,which are peptidoglycan hydrolases encoded by double-stranded DNA bacteriophage, are produced in phage-infected bacterial cells toward the end of the lytic cycle. It was proved that the phage lysins exhibited high activity against bacteria, narrow antibacterial spectrum, and apparent safety in vitro and vivo experiments. Those paved solid foundation for further exploration of their application. A review on the structure and mode of action of lysins and their application were presented.
More recently, the original application of phage as therapeutics to treat human and animal infections has been rekindled, particularly in an era where antibiotic resistance has become so problematic. Bacteriophage lysins,which are peptidoglycan hydrolases encoded by double-stranded DNA bacteriophage, are produced in phage-infected bacterial cells toward the end of the lytic cycle. It was proved that the phage lysins exhibited high activity against bacteria, narrow antibacterial spectrum, and apparent safety in vitro and vivo experiments. Those paved solid foundation for further exploration of their application. A review on the structure and mode of action of lysins and their application were presented.
引文
[1] ABENDON S T,GARCíA P,MULLANY P,et al. Editorial:Phage therapy:Past,present and future[J].Front Microbiol,2017,8:981.
[2] BRüSSOW H. What is needed for phage therapy to become a reality in western medicine?[J].Virology,2012,434(2):138-142.
[3] AJUEBOR J,MCAULIFFE O,O'MAHONY J,et al. Bacteriophage endolysins and their applications[J].Science progress,2016,99(2):183-199.
[4] PASTAGIA M,SCHUCH R,FISCHETTI V A,et al. Lysins:The arrival of pathogen-directed anti-infectives[J].Journal of medical microbiology,2013,62:1506-1516.
[5] GERSTMANS H,CRIEL B,BRIERS Y.Synthetic biology of modular endolysins[J].Biotechnol Adv,2018,36(3):624-640.
[6] RODRIGUEZ L,MARTINEZ B,ZHOU Y,et al. Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureus bacteriophage v B_SauS-philPLA88[J]. BMC Microbiol,2011,11:138.
[7] FISCHETTI V A. Bacteriophage endolysins:A novel anti-infective to control gram-positive pathogens[J].International journal of medical microbiology,2010,300(6):357-362.
[8] YOUNG R. Bacteriophage lysis-mechanism and regulation[J].Microbiological reviews,1992,56(3):430-481.
[9] PAYNE K,SUN Q,SACCHETTINI J,et al. Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase[J].Molecular microbiology,2009,73(3):367-381.
[10] NELSON D,LOOMIS L,FISCHETTI V A. Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme[J].PNAS,2001,98(7):4107-4112.
[11] LOEFFLER J M,DJURKOVIC S,FISCHETTI V A. Phage lytic enzyme Cpl-1 as a novel antimicrobial for pneumococcal bacteremia[J].Infection and immunity,2003,71(11):6199-6204.
[12] DEUTSCH S M,GUEZENEC S,PIOT M,et al. Mur-LH,the broad-spectrum endolysin of Lactobacillus helveticus temperate bacteriophage准-0303[J].Applied and environmental microbiology,2004,70(1):96-103.
[13] SCHMITZ J E,OSSIPRANDI M C,RUMAH K R,et al. Lytic enzyme discovery through multigenomic sequence analysis in Clostridium perfringens[J].Applied microbiology and biotechnology,2011,89(6):1783-1795.
[14] QIAO J J,LI Y P,WEI C H,et al. Rapid detection of viral antibodies based on multifunctional Staphylococcus aureus nanobioprobes[J].Enzyme and microbial technology,2016,95:94-99.
[15] YANG H,XU J,LI W,et al. Staphylococcus aureus virulence attenuation and immune clearance mediated by a phage lysinderived protein[J].EMBO J,2018,37(17):e98045.
[16] YU J,ZHANG Y,ZHANG Y,et al. Sensitive and rapid detection of Staphylococcus aureus in milk via cell binding domain of lysin[J].Biosensors&bioelectronics,2016,77:366-371.
[17] LIU J,ZHANG X,YANG H,et al. Study of the interactions between endolysin and bacterial peptidoglycan on S. aureus by dynamic force spectroscopy[J].Nanoscale,2015,7(37):15245-15250.
[18] RASHEL M,UCHIYAMA J,UJIHARA T,et al. Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage OMR11[J].Journal of infectious diseases,2007,196(8):1237-1247.
[19] LOESSNER M J,KRAMER K,EBEL F,et al. C-terminal domains of Listeria monocytogenes bacteriophage murein hydrolases determine specific recognition and high-affinity binding to bacterial cell wall carbohydrates[J].Molecular microbiology,2002,44(2):335-349.
[20] SHI Y B,LI N,YAN Y X,et al. Combined antibacterial activity of phage lytic proteins holin and lysin from Streptococcus suis bacteriophage SMP[J].Current microbiology,2012,65:28-34.
[21] JADO I,LóPEZ R,GARCíA E,et al. Phage lytic enzymes as therapy for antibiotic-resistant Streptococcus pneumoniae infection in a murine sepsis model[J]. Journal of antimicrobial chemotherapy,2003,52(6):967-973.
[22] DJURKOVIC S,LOEFFLER J M,FISCHETTI V A. Synergistic killing of Streptococcus pneumoniae with the bacteriophage lytic enzyme Cpl-1 and penicillin or gentamicin depends on the level of penicillin resistance[J].Antimicrob agents chemother,2005,49(3):1225-1228.
[23] CROUX C,RONDA C,LóPEZ R,et al. Interchange of functional domains switches enzyme specificity:Construction of a chimeric pneumococcal-clostridial cell wall lytic enzyme[J].Mol Microbiol,1993,9(5):1019-1025.
[24] OSHIDA T,SUGAI M,KOMATSUZAWA H,et al. A Staphylococcus aureus autolysin that has an N-acetylmuramoyl-L-alanine amidase domain and an endo-beta-N-acetylglucosaminidase domain:Cloning,sequence analysis,and characterization[J].Proc Natl Acad Sci USA,1995,92(1):285-289.
[25] SHEEHAN M M,GARCíJ,LóPEZ R,et al. Analysis of the catalytic domain of the lysin of the lactococcal bacteriophage Tuc2009 by chimeric gene assembling[J].FEMS Microbiol Lett,1996, 140(1):23-28.
[26] MILOHANIC E,JONQUIèRES R,COSSART P,et al. The autolysin Ami contributes to the adhesion of Listeria monocytogenes to eukaryotic cells via its cell wall anchor[J].Mol Microbiol,2001,39(5):1212-1224.
[27] BECKER S C,FOSTER-FREY J,STODOLA A J,et al. Differentially conserved staphylococcal SH3b_5 cell wall binding domains confer increased staphylolytic and streptolytic activity to a streptococcal prophage endolysin domain[J].Gene,2009,443(1-2):32-41.
[28] HORGAN M,O'FLYNN G,GARRY J,et al. Phage lysin LysK can be truncated to its CHAP domain and retain lytic activity against live antibiotic-resistant staphylococci[J].Appl Environ Microbiol,2009,75(3):872-874.
[29] SINGH P K,DONOVAN D M,KUMAR A. Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from Staphylococcus aureus endophthalmitis[J].Antimicrobial agents and chemotherapy,2014,58(8):4621-4629.
[30] SCHMELCHER M,SHABAROVA T,EUGSTER M R,et al.Rapid multiplex detection and differentiation of Listeria cells by use of fluorescent phage endolysin cell wall binding domains[J].Applied and environmental microbiology,2010,76(17):5745-5756.
[31] SCHOLTE C M,NELSON D C,GARCIA M,et al. Short communication:Recombinant bacteriophage endolysin PlyC is nontoxic and does not alter blood neutrophil oxidative response in lactating dairy cows[J].Journal of dairy science,2018,101(7):6419-6423.
[32] YANG H,WANG M,YU J,et al. Antibacterial activity of a novel peptide-modified lysin against Acinetobacter baumannii and Pseudomonas aeruginosa[J].Frontiers in microbiology,2015,6:1471.
[33] YANG H,BI Y,SHANG X,et al. Antibiofilm activities of a novel chimeolysin against Streptococcus mutans under physiological and cariogenic conditions[J].Antimicrob agents chemother,2016,60(12):7436-7443.
[34] ALI S B,DIVIèS C,PRéVOST H. Genetic organization of the citCDEF locus and identification of mae and clyR genes from Leuconostoc mesenteroides[J].J Bacteriol,1999,181(14):4411-4416.
[35] WANG S,GU J,LV M,et al.,The antibacterial activity of Ecoli bacteriophage lysin lysep3 is enhanced by fusing the Bacillus amyloliquefaciens bacteriophage endolysin binding domain D8 to the C-terminal region[J].Journal of microbiology,2017,55(5):403-408.
[36] YANG H,YU J,WEI H. Engineered bacteriophage lysins as novel anti-infectives[J].Front Microbiol,2014,5:542.
[37] VAREA J,MONTERROSO B,SáIZ J L,et al. Structural and thermodynamic characterization of Pal,a phage natural chimeric lysin active against pneumococci[J].Journal of biological chemistry,2004,279(42):43697-43707.
[38] SCHMELCHER M,KOROBOVA O,SCHISCHKOVA N,et al.Staphylococcus haemolyticus prophage准SH2 endolysin relies on cysteine, histidine-dependent amidohydrolases/peptidases activity for lysis ‘from without’[J].Journal of biotechnology,2012,162(2-3):289-298.
[39] RAZ A,SERRANO A,LAWSON C,et al. Lysibodies are IgG Fc fusions with lysin binding domains targeting Staphylococcus aureus wall carbohydrates for effective phagocytosis[J].PNAS,2017,114(18):4781-4786.
[40] MA Q,GUO Z M,GAO C C,et al. Enhancement of the direct antimicrobial activity of Lysep3 against Escherichia coli by inserting cationic peptides into its C terminus[J].Antonie van leeuwenhoek,2017,110(3):347-355.
[41] ENTENZA J M,LOEFFLER J M,GRANDGIRARD D,et al.Therapeutic effects of bacteriophage Cpl-1 lysin against Streptococcus pneumoniae endocarditis in rats[J].Antimicrobial agents and chemotherapy,2005,49(11):4789-4792.
[42]王铮,沈文彬,张浩天,等.噬菌体裂解酶作为抗菌药物的研究进展[J].上海交通大学学报(医学版),2013,33(3):368-373.
[43]王琰,陆承平.噬菌体裂解酶的抗菌特性[J].微生物学报,2009,49(10):1277-1281.
[2] BRüSSOW H. What is needed for phage therapy to become a reality in western medicine?[J].Virology,2012,434(2):138-142.
[3] AJUEBOR J,MCAULIFFE O,O'MAHONY J,et al. Bacteriophage endolysins and their applications[J].Science progress,2016,99(2):183-199.
[4] PASTAGIA M,SCHUCH R,FISCHETTI V A,et al. Lysins:The arrival of pathogen-directed anti-infectives[J].Journal of medical microbiology,2013,62:1506-1516.
[5] GERSTMANS H,CRIEL B,BRIERS Y.Synthetic biology of modular endolysins[J].Biotechnol Adv,2018,36(3):624-640.
[6] RODRIGUEZ L,MARTINEZ B,ZHOU Y,et al. Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureus bacteriophage v B_SauS-philPLA88[J]. BMC Microbiol,2011,11:138.
[7] FISCHETTI V A. Bacteriophage endolysins:A novel anti-infective to control gram-positive pathogens[J].International journal of medical microbiology,2010,300(6):357-362.
[8] YOUNG R. Bacteriophage lysis-mechanism and regulation[J].Microbiological reviews,1992,56(3):430-481.
[9] PAYNE K,SUN Q,SACCHETTINI J,et al. Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase[J].Molecular microbiology,2009,73(3):367-381.
[10] NELSON D,LOOMIS L,FISCHETTI V A. Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme[J].PNAS,2001,98(7):4107-4112.
[11] LOEFFLER J M,DJURKOVIC S,FISCHETTI V A. Phage lytic enzyme Cpl-1 as a novel antimicrobial for pneumococcal bacteremia[J].Infection and immunity,2003,71(11):6199-6204.
[12] DEUTSCH S M,GUEZENEC S,PIOT M,et al. Mur-LH,the broad-spectrum endolysin of Lactobacillus helveticus temperate bacteriophage准-0303[J].Applied and environmental microbiology,2004,70(1):96-103.
[13] SCHMITZ J E,OSSIPRANDI M C,RUMAH K R,et al. Lytic enzyme discovery through multigenomic sequence analysis in Clostridium perfringens[J].Applied microbiology and biotechnology,2011,89(6):1783-1795.
[14] QIAO J J,LI Y P,WEI C H,et al. Rapid detection of viral antibodies based on multifunctional Staphylococcus aureus nanobioprobes[J].Enzyme and microbial technology,2016,95:94-99.
[15] YANG H,XU J,LI W,et al. Staphylococcus aureus virulence attenuation and immune clearance mediated by a phage lysinderived protein[J].EMBO J,2018,37(17):e98045.
[16] YU J,ZHANG Y,ZHANG Y,et al. Sensitive and rapid detection of Staphylococcus aureus in milk via cell binding domain of lysin[J].Biosensors&bioelectronics,2016,77:366-371.
[17] LIU J,ZHANG X,YANG H,et al. Study of the interactions between endolysin and bacterial peptidoglycan on S. aureus by dynamic force spectroscopy[J].Nanoscale,2015,7(37):15245-15250.
[18] RASHEL M,UCHIYAMA J,UJIHARA T,et al. Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage OMR11[J].Journal of infectious diseases,2007,196(8):1237-1247.
[19] LOESSNER M J,KRAMER K,EBEL F,et al. C-terminal domains of Listeria monocytogenes bacteriophage murein hydrolases determine specific recognition and high-affinity binding to bacterial cell wall carbohydrates[J].Molecular microbiology,2002,44(2):335-349.
[20] SHI Y B,LI N,YAN Y X,et al. Combined antibacterial activity of phage lytic proteins holin and lysin from Streptococcus suis bacteriophage SMP[J].Current microbiology,2012,65:28-34.
[21] JADO I,LóPEZ R,GARCíA E,et al. Phage lytic enzymes as therapy for antibiotic-resistant Streptococcus pneumoniae infection in a murine sepsis model[J]. Journal of antimicrobial chemotherapy,2003,52(6):967-973.
[22] DJURKOVIC S,LOEFFLER J M,FISCHETTI V A. Synergistic killing of Streptococcus pneumoniae with the bacteriophage lytic enzyme Cpl-1 and penicillin or gentamicin depends on the level of penicillin resistance[J].Antimicrob agents chemother,2005,49(3):1225-1228.
[23] CROUX C,RONDA C,LóPEZ R,et al. Interchange of functional domains switches enzyme specificity:Construction of a chimeric pneumococcal-clostridial cell wall lytic enzyme[J].Mol Microbiol,1993,9(5):1019-1025.
[24] OSHIDA T,SUGAI M,KOMATSUZAWA H,et al. A Staphylococcus aureus autolysin that has an N-acetylmuramoyl-L-alanine amidase domain and an endo-beta-N-acetylglucosaminidase domain:Cloning,sequence analysis,and characterization[J].Proc Natl Acad Sci USA,1995,92(1):285-289.
[25] SHEEHAN M M,GARCíJ,LóPEZ R,et al. Analysis of the catalytic domain of the lysin of the lactococcal bacteriophage Tuc2009 by chimeric gene assembling[J].FEMS Microbiol Lett,1996, 140(1):23-28.
[26] MILOHANIC E,JONQUIèRES R,COSSART P,et al. The autolysin Ami contributes to the adhesion of Listeria monocytogenes to eukaryotic cells via its cell wall anchor[J].Mol Microbiol,2001,39(5):1212-1224.
[27] BECKER S C,FOSTER-FREY J,STODOLA A J,et al. Differentially conserved staphylococcal SH3b_5 cell wall binding domains confer increased staphylolytic and streptolytic activity to a streptococcal prophage endolysin domain[J].Gene,2009,443(1-2):32-41.
[28] HORGAN M,O'FLYNN G,GARRY J,et al. Phage lysin LysK can be truncated to its CHAP domain and retain lytic activity against live antibiotic-resistant staphylococci[J].Appl Environ Microbiol,2009,75(3):872-874.
[29] SINGH P K,DONOVAN D M,KUMAR A. Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from Staphylococcus aureus endophthalmitis[J].Antimicrobial agents and chemotherapy,2014,58(8):4621-4629.
[30] SCHMELCHER M,SHABAROVA T,EUGSTER M R,et al.Rapid multiplex detection and differentiation of Listeria cells by use of fluorescent phage endolysin cell wall binding domains[J].Applied and environmental microbiology,2010,76(17):5745-5756.
[31] SCHOLTE C M,NELSON D C,GARCIA M,et al. Short communication:Recombinant bacteriophage endolysin PlyC is nontoxic and does not alter blood neutrophil oxidative response in lactating dairy cows[J].Journal of dairy science,2018,101(7):6419-6423.
[32] YANG H,WANG M,YU J,et al. Antibacterial activity of a novel peptide-modified lysin against Acinetobacter baumannii and Pseudomonas aeruginosa[J].Frontiers in microbiology,2015,6:1471.
[33] YANG H,BI Y,SHANG X,et al. Antibiofilm activities of a novel chimeolysin against Streptococcus mutans under physiological and cariogenic conditions[J].Antimicrob agents chemother,2016,60(12):7436-7443.
[34] ALI S B,DIVIèS C,PRéVOST H. Genetic organization of the citCDEF locus and identification of mae and clyR genes from Leuconostoc mesenteroides[J].J Bacteriol,1999,181(14):4411-4416.
[35] WANG S,GU J,LV M,et al.,The antibacterial activity of Ecoli bacteriophage lysin lysep3 is enhanced by fusing the Bacillus amyloliquefaciens bacteriophage endolysin binding domain D8 to the C-terminal region[J].Journal of microbiology,2017,55(5):403-408.
[36] YANG H,YU J,WEI H. Engineered bacteriophage lysins as novel anti-infectives[J].Front Microbiol,2014,5:542.
[37] VAREA J,MONTERROSO B,SáIZ J L,et al. Structural and thermodynamic characterization of Pal,a phage natural chimeric lysin active against pneumococci[J].Journal of biological chemistry,2004,279(42):43697-43707.
[38] SCHMELCHER M,KOROBOVA O,SCHISCHKOVA N,et al.Staphylococcus haemolyticus prophage准SH2 endolysin relies on cysteine, histidine-dependent amidohydrolases/peptidases activity for lysis ‘from without’[J].Journal of biotechnology,2012,162(2-3):289-298.
[39] RAZ A,SERRANO A,LAWSON C,et al. Lysibodies are IgG Fc fusions with lysin binding domains targeting Staphylococcus aureus wall carbohydrates for effective phagocytosis[J].PNAS,2017,114(18):4781-4786.
[40] MA Q,GUO Z M,GAO C C,et al. Enhancement of the direct antimicrobial activity of Lysep3 against Escherichia coli by inserting cationic peptides into its C terminus[J].Antonie van leeuwenhoek,2017,110(3):347-355.
[41] ENTENZA J M,LOEFFLER J M,GRANDGIRARD D,et al.Therapeutic effects of bacteriophage Cpl-1 lysin against Streptococcus pneumoniae endocarditis in rats[J].Antimicrobial agents and chemotherapy,2005,49(11):4789-4792.
[42]王铮,沈文彬,张浩天,等.噬菌体裂解酶作为抗菌药物的研究进展[J].上海交通大学学报(医学版),2013,33(3):368-373.
[43]王琰,陆承平.噬菌体裂解酶的抗菌特性[J].微生物学报,2009,49(10):1277-1281.