Enzybiotics: a look to the future, recalling the past.

The discovery and development of antibiotics was one of the greatest successes of Medicine in the 20th century and allowed the control of many diseases caused by microorganisms. Nevertheless, it is necessary to search constantly for new therapeutic tools in the continuing fight against disease-causing microorganisms and this probably leads us to today's concept of enzybiotics. Although microorganism-degrading enzymes have been known since the beginning of the last century, their use was soon forgotten because of the widespread use of antibiotics. The term enzybiotic is a hybrid word from "enzyme" and "antibiotic" and refers to phages: that is, viruses that attack and lyse bacteria and that can potentially help us to fight bacterial diseases. If the concept of enzybiotic is extended to antifungal enzymes, an enormous potential in the struggle against microorganism-due diseases may become available in the foreseeable future.

[1]  A. Place,et al.  Identification of a Novel Acidic Mammalian Chitinase Distinct from Chitotriosidase* , 2001, The Journal of Biological Chemistry.

[2]  U. Bläsi,et al.  Phage P68 Virion-Associated Protein 17 Displays Activity against Clinical Isolates of Staphylococcus aureus , 2005, Antimicrobial Agents and Chemotherapy.

[3]  J. Dolan,et al.  Use of Genetically Engineered Phage To Deliver Antimicrobial Agents to Bacteria: an Alternative Therapy for Treatment of Bacterial Infections , 2003, Antimicrobial Agents and Chemotherapy.

[4]  E. Block,et al.  Pharmacological Studies with 5-Fluorocytosine , 1972, Antimicrobial Agents and Chemotherapy.

[5]  E. Bakienė,et al.  Penetration of Enveloped Double-Stranded RNA Bacteriophages φ13 and φ6 into Pseudomonas syringae Cells , 2005, Journal of Virology.

[6]  H. Bussey,et al.  KRE5 Gene Null Mutant Strains of Candida albicans Are Avirulent and Have Altered Cell Wall Composition and Hypha Formation Properties , 2004, Eukaryotic Cell.

[7]  David J Adams,et al.  Fungal cell wall chitinases and glucanases. , 2004, Microbiology.

[8]  I. Wang,et al.  Holins: the protein clocks of bacteriophage infections. , 2000, Annual review of microbiology.

[9]  H Verhagen,et al.  Safety evaluation of beta-glucanase derived from Trichoderma reesei: summary of toxicological data. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[10]  G. A. Vikhoreva,et al.  Comparison of antithrombin activity of the polysulphate chitosan derivatives in in vivo and in vitro system. , 2001, Thrombosis research.

[11]  R. Homer,et al.  Chitinases and chitinase-like proteins in T(H)2 inflammation and asthma. , 2005, The Journal of allergy and clinical immunology.

[12]  A. Sulakvelidze Phage therapy: an attractive option for dealing with antibiotic-resistant bacterial infections. , 2005, Drug discovery today.

[13]  C. Ronda,et al.  Los bacteriófagos como herramienta para combatir infecciones en Acuicultura , 2003 .

[14]  J. M. Scholtz,et al.  Purification and Biochemical Characterization of the Lambda Holin , 1998, Journal of bacteriology.

[15]  I. Wang,et al.  Phages will out: strategies of host cell lysis. , 2000, Trends in microbiology.

[16]  J. García,et al.  The pneumococcal cell wall degrading enzymes: a modular design to create new lysins? , 1997, Microbial drug resistance.

[17]  V. Fischetti,et al.  Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P Buri,et al.  Chitosan: a unique polysaccharide for drug delivery. , 1998, Drug development and industrial pharmacy.

[19]  Vincent A. Fischetti,et al.  Removal of Group B Streptococci Colonizing the Vagina and Oropharynx of Mice with a Bacteriophage Lytic Enzyme , 2005, Antimicrobial Agents and Chemotherapy.

[20]  S. Projan Phage-inspired antibiotics? , 2004, Nature Biotechnology.

[21]  Ernesto García,et al.  Phage lytic enzymes as therapy for antibiotic-resistant Streptococcus pneumoniae infection in a murine sepsis model. , 2003, The Journal of antimicrobial chemotherapy.

[22]  K. Igarashi,et al.  Gene Cloning and Heterologous Expression of Glycoside Hydrolase Family 55 β-1,3-Glucanase from the Basidiomycete Phanerochaete Chrysosporium , 2006, Biotechnology Letters.

[23]  V. Fischetti,et al.  Synergistic Lethal Effect of a Combination of Phage Lytic Enzymes with Different Activities on Penicillin-Sensitive and -Resistant Streptococcus pneumoniae Strains , 2003, Antimicrobial Agents and Chemotherapy.

[24]  M. Sinnott,et al.  Catalytic mechanism of enzymic glycosyl transfer , 1990 .

[25]  Manisha Chawla,et al.  Chitosan: some pharmaceutical and biological aspects ‐ an update , 2001, The Journal of pharmacy and pharmacology.

[26]  B. Masschalck,et al.  Comparison of bactericidal activity of six lysozymes at atmospheric pressure and under high hydrostatic pressure. , 2006, International journal of food microbiology.

[27]  Vincent A. Fischetti,et al.  Rapid Killing of Streptococcus pneumoniae with a Bacteriophage Cell Wall Hydrolase , 2001, Science.

[28]  Beatriz Galán,et al.  Structural basis for selective recognition of pneumococcal cell wall by modular endolysin from phage Cp-1. , 2003, Structure.

[29]  D. Duckworth "Who discovered bacteriophage?". , 1976, Bacteriological reviews.

[30]  R. E. Huber,et al.  Site-directed mutagenesis of beta-galactosidase (E. coli) reveals that tyr-503 is essential for activity. , 1988, Biochemical and biophysical research communications.

[31]  Raymond Schuch,et al.  A bacteriolytic agent that detects and kills Bacillus anthracis , 2002, Nature.

[32]  M. F. D'Herelle Sur un microbe invisible antagoniste des bacilles dysenteriques , 1961 .

[33]  U. Bläsi,et al.  Genetically modified filamentous phage as bactericidal agents: a pilot study , 2003, Letters in applied microbiology.

[34]  C. Merril,et al.  Bacteriophage Therapy Rescues Mice Bacteremic from a Clinical Isolate of Vancomycin-Resistant Enterococcus faecium , 2002, Infection and Immunity.

[35]  V. Fischetti,et al.  Bacteriophage lytic enzymes: novel anti-infectives. , 2005, Trends in microbiology.

[36]  U. Bläsi,et al.  Dimerization between the Holin and Holin Inhibitor of Phage λ , 2000, Journal of bacteriology.

[37]  J. Norris,et al.  Prokaryotic gene therapy to combat multidrug resistant bacterial infection , 2000, Gene Therapy.

[38]  Andre Boorsma,et al.  Cell wall construction in Saccharomyces cerevisiae , 2006, Yeast.

[39]  Rupinder Tewari,et al.  Biotechnological aspects of chitinolytic enzymes: a review , 2006, Applied Microbiology and Biotechnology.

[40]  R. Weiner,et al.  Detection and characterization of chitinases and other chitin-modifying enzymes , 2003, Journal of Industrial Microbiology and Biotechnology.

[41]  M. Morange,et al.  Book reviews-Felix d'herelle and the origins of molecular biology , 1999 .

[42]  F. Twort AN INVESTIGATION ON THE NATURE OF ULTRA-MICROSCOPIC VIRUSES. , 1915 .

[43]  D. Davies,et al.  The influence of carbohydrases on the growth of fungal pathogens in vitro and in vivo. , 1979, Postgraduate medical journal.