Peptidoglycan hydrolases-potential weapons against Staphylococcus aureus

Bacteria of the genus Staphylococcus are common pathogens responsible for a broad spectrum of human and animal infections and belong to the most important etiological factors causing food poisoning. Because of rapid increase in the prevalence of isolation of staphylococci resistant to many antibiotics, there is an urgent need for the development of new alternative chemotherapeutics. A number of studies have recently demonstrated the strong potential of peptidoglycan hydrolases (PHs) to control and treat infections caused by this group of bacteria. PHs cause rapid lysis and death of bacterial cells. The review concentrates on enzymes hydrolyzing peptidoglycan of staphylococci. Usually, they are characterized by high specificity to only Staphylococcus aureus cell wall components; however, some of them are also able to lyse cells of other staphylococci, e.g., Staphylococcus epidermidis-human pathogen of growing importance and also other groups of bacteria. Some PHs strengthen the bactericidal or bacteriostatic activity of common antibiotics, and as a result, they should be considered as component of combined therapy which could definitely reduced the development of bacterial resistance to both enzymes and antibiotics. The preliminary research revealed that most of these enzymes can be produced using heterologous, especially Escherichia coli expression systems; however, still much effort is required to develop more efficient and large-scale production technologies. This review discusses current state on knowledge with emphasis on the possibilities of application of PHs in the context of therapeutics for infections caused by staphylococci.

[1]  C. Hill,et al.  The truncated phage lysin CHAPk eliminates Staphylococcus aureus in the nares of mice , 2010, Bioengineered bugs.

[2]  E. Oldham,et al.  Lysostaphin: use of a recombinant bactericidal enzyme as a mastitis therapeutic. , 1991, Journal of dairy science.

[3]  M. Bochtler,et al.  Crystal structures of active LytM. , 2005, Journal of molecular biology.

[4]  Vincent A. Fischetti,et al.  Gram-positive pathogens , 2006 .

[5]  J. Fink-Gremmels,et al.  Extended antimicrobial susceptibility assay for Staphylococcus aureus isolates from bovine mastitis growing in biofilms. , 2007, Veterinary microbiology.

[6]  J. Suárez,et al.  Prevalence of bacteriophages infecting Staphylococcus aureus in dairy samples and their potential as biocontrol agents. , 2009, Journal of dairy science.

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

[8]  David L. Smith,et al.  Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005 , 2007, Emerging infectious diseases.

[9]  Julie A. Wu,et al.  Lysostaphin Disrupts Staphylococcus aureus and Staphylococcus epidermidis Biofilms on Artificial Surfaces , 2003, Antimicrobial Agents and Chemotherapy.

[10]  F. Götz,et al.  Evidence for autolysin‐mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface , 1997, Molecular microbiology.

[11]  G. Shockman,et al.  Chapter 7 Microbial peptidoglycan (murein) hydrolases , 1994 .

[12]  D. Ohman,et al.  Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis , 2012, Graefe's Archive for Clinical and Experimental Ophthalmology.

[13]  D. Patel,et al.  Staphylococcal superantigen super-domains in immune evasion. , 2010, Critical reviews in immunology.

[14]  B. Martínez,et al.  Synergy between the phage endolysin LysH5 and nisin to kill Staphylococcus aureus in pasteurized milk. , 2010, International journal of food microbiology.

[15]  A. Coffey,et al.  Recombinant bacteriophage lysins as antibacterials , 2010, Bioengineered bugs.

[16]  P. M. Pereira,et al.  Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus , 2010, Proceedings of the National Academy of Sciences.

[17]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[18]  F. Lowy Antimicrobial resistance: the example of Staphylococcus aureus. , 2003, The Journal of clinical investigation.

[19]  M. Bartoszcze,et al.  Characterization of a bacteriophage, isolated from a cow with mastitis, that is lytic against Staphylococcus aureus strains , 2011, Archives of Virology.

[20]  M. Paape,et al.  Genetically enhanced cows resist intramammary Staphylococcus aureus infection , 2005, Nature Biotechnology.

[21]  W. Kloos,et al.  Identification of "Staphylococcus staphylolyticus" NRRL B-2628 as a Biovar of Staphylococcus simulans , 1982 .

[22]  P. Blackburn,et al.  In vitro activity of recombinant lysostaphin-antibiotic combinations toward methicillin-resistant Staphylococcus aureus. , 1993, Diagnostic microbiology and infectious disease.

[23]  F. Götz,et al.  The Presence of Peptidoglycan O-Acetyltransferase in Various Staphylococcal Species Correlates with Lysozyme Resistance and Pathogenicity , 2006, Infection and Immunity.

[24]  W. Grubb,et al.  Genetic analysis of community isolates of methicillin-resistant Staphylococcus aureus in Western Australia. , 1993, The Journal of hospital infection.

[25]  J. Rossi,et al.  Effect of Enrichment Procedure upon Auxotroph Recovery in Escherichia coli K-12 , 1975, Antimicrobial Agents and Chemotherapy.

[26]  F. Götz,et al.  The molecular organization of the lysostaphin gene and its sequences repeated in tandem , 1987, Molecular and General Genetics MGG.

[27]  R. Kane,et al.  Lysostaphin-functionalized cellulose fibers with antistaphylococcal activity for wound healing applications. , 2011, Biomaterials.

[28]  K. LaPlante In vitro activity of lysostaphin, mupirocin, and tea tree oil against clinical methicillin-resistant Staphylococcus aureus. , 2007, Diagnostic microbiology and infectious disease.

[29]  V. Fischetti,et al.  Bacteriophage lysins as effective antibacterials. , 2008, Current opinion in microbiology.

[30]  W. Han,et al.  LysGH15 reduces the inflammation caused by lethal methicillin-resistant Staphylococcus aureus infection in mice , 2011, Bioengineered bugs.

[31]  B. Martínez,et al.  Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88 , 2011, BMC Microbiology.

[32]  S. Walsh,et al.  Lysostaphin Cream Eradicates Staphylococcus aureus Nasal Colonization in a Cotton Rat Model , 2003, Antimicrobial Agents and Chemotherapy.

[33]  G. Archer,et al.  Lysostaphin Treatment of Experimental Methicillin-Resistant Staphylococcus aureus Aortic Valve Endocarditis , 1998, Antimicrobial Agents and Chemotherapy.

[34]  D. Ohman,et al.  Evaluation of Pseudomonas aeruginosa staphylolysin (LasA protease) in the treatment of methicillin-resistant Staphylococcus aureus endophthalmitis in a rat model , 2009, Graefe's Archive for Clinical and Experimental Ophthalmology.

[35]  Hume,et al.  Lysostaphin treatment of methicillin-resistant staphylococcus aureus keratitis in the rabbit(1) , 2000, American journal of ophthalmology.

[36]  W. Hammes,et al.  Cloning and expression of the lysostaphin gene in Bacillus subtilis and Lactobadllus casei , 1992 .

[37]  J. Fink-Gremmels,et al.  Comparative assessment of the antimicrobial susceptibility of Staphylococcus aureus isolates from bovine mastitis in biofilm versus planktonic culture. , 2006, Journal of veterinary medicine. B, Infectious diseases and veterinary public health.

[38]  Y. Prasad,et al.  Efficacy of Polyvalent Bacteriophage P-27/HP to Control Multidrug Resistant Staphylococcus aureus Associated with Human Infections , 2010, Current Microbiology.

[39]  C. Schindler,et al.  LYSOSTAPHIN: A NEW BACTERIOLYTIC AGENT FOR THE STAPHYLOCOCCUS. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Ravi S Kane,et al.  Antistaphylococcal nanocomposite films based on enzyme-nanotube conjugates. , 2010, ACS nano.

[41]  R. Daum,et al.  Development of vancomycin and lysostaphin resistance in a methicillin-resistant Staphylococcus aureus isolate. , 2001, The Journal of antimicrobial chemotherapy.

[42]  Guodong Li,et al.  Extension of nasal anti-Staphylococcus aureus efficacy of lysostaphin by its incorporation into a chitosan-o/w cream , 2010, Drug delivery.

[43]  F. Milder,et al.  Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications , 2010, Journal of Molecular Medicine.

[44]  J. Robinson,et al.  Relationship between lysostaphin endopeptidase production and cell wall composition in Staphylococcus staphylolyticus , 1979, Journal of bacteriology.

[45]  D. Rubin,et al.  Methicillin resistant staphylococci. , 1971, JAMA.

[46]  K. Honke,et al.  Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage phi MR11. , 2007, The Journal of infectious diseases.

[47]  J. Kur,et al.  New effective sources of the Staphylococcus simulans lysostaphin. , 2005, Journal of biotechnology.

[48]  W. Xu,et al.  LysGH15, a Novel Bacteriophage Lysin, Protects a Murine Bacteremia Model Efficiently against Lethal Methicillin-Resistant Staphylococcus aureus Infection , 2010, Journal of Clinical Microbiology.

[49]  R. O'Callaghan,et al.  Immunity to lysostaphin and its therapeutic value for ocular MRSA infections in the rabbit. , 2002, Investigative ophthalmology & visual science.

[50]  F. Haesebrouck,et al.  Methicillin-resistant Staphylococcus aureus (MRSA) in food production animals , 2010, Epidemiology and Infection.

[51]  R. Sessions,et al.  Crystal structure of the LasA virulence factor from Pseudomonas aeruginosa: substrate specificity and mechanism of M23 metallopeptidases. , 2010, Journal of molecular biology.

[52]  Paul D. R. Johnson,et al.  Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications , 2010, Clinical Microbiology Reviews.

[53]  A. Coffey,et al.  Characterization of the staphylococcal bacteriophage lysin CHAPK , 2011, Journal of applied microbiology.

[54]  D. Ohman,et al.  Pseudomonas aeruginosa LasA Protease in Treatment of Experimental Staphylococcal Keratitis , 2004, Antimicrobial Agents and Chemotherapy.

[55]  A. Tomasz,et al.  Perturbation of Cell Wall Synthesis Suppresses Autolysis in Staphylococcus aureus: Evidence for Coregulation of Cell Wall Synthetic and Hydrolytic Enzymes , 2007, Journal of bacteriology.

[56]  Henry F. Chambers,et al.  Waves of resistance: Staphylococcus aureus in the antibiotic era , 2009, Nature Reviews Microbiology.

[57]  Jan Borysowski,et al.  Bacteriophage Endolysins as a Novel Class of Antibacterial Agents , 2006, Experimental biology and medicine.

[58]  S. G. Odintsov,et al.  Latent LytM at 1.3A resolution. , 2004, Journal of molecular biology.

[59]  Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus — Minnesota and North Dakota, 1997-1999. , 1999, MMWR. Morbidity and mortality weekly report.

[60]  W. Lane METHICILLIN RESISTANCE IN STAPHYLOCOCCI , 1962, The Medical journal of Australia.

[61]  G. Pier,et al.  Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence , 2001, Nature.

[62]  Chad W. Euler,et al.  Synergism between a Novel Chimeric Lysin and Oxacillin Protects against Infection by Methicillin-Resistant Staphylococcus aureus , 2010, Antimicrobial Agents and Chemotherapy.

[63]  J. Saulnier,et al.  Hydrolysis of glycine-containing elastin pentapeptides by LasA, a metalloelastase from Pseudomonas aeruginosa. , 2001, European journal of biochemistry.

[64]  E. T. Çetin,et al.  Staphylococci Resistant to Methicillin (“Celbenin”) , 1962 .

[65]  John D. Lambris,et al.  Complement evasion by human pathogens , 2008, Nature Reviews Microbiology.

[66]  D. Missiakas,et al.  Staphylococcus aureus Mutants with Increased Lysostaphin Resistance , 2006, Journal of bacteriology.

[67]  Anil Kumar Singh,et al.  Identification and characterization of a vancomycin-resistant Staphylococcus aureus isolated from Kolkata (South Asia). , 2008, Journal of medical microbiology.

[68]  A. Tomasz,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. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[69]  S. Taiwo Methicillin resistance in Staphylococcus aureus: a review of the molecular epidemiology, clinical significance and laboratory detection methods. , 2010, West African journal of medicine.

[70]  R. Mecham,et al.  Binding and degradation of elastin by the staphylolytic enzyme lysostaphin. , 1995, International Journal of Biochemistry and Cell Biology.

[71]  D. Gutiérrez,et al.  Lytic Activity of LysH5 Endolysin Secreted by Lactococcus lactis Using the Secretion Signal Sequence of Bacteriocin Lcn972 , 2012, Applied and Environmental Microbiology.

[72]  E. Smid,et al.  Industrial-scale production and purification of a heterologous protein in Lactococcus lactis using the nisin-controlled gene expression system NICE: The case of lysostaphin , 2005, Microbial cell factories.

[73]  U. Bläsi,et al.  Holins: form and function in bacteriophage lysis. , 1995, FEMS microbiology reviews.

[74]  F. Tenover,et al.  Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. , 1997, The Journal of antimicrobial chemotherapy.

[75]  W. Schröder,et al.  Site-Specific Serine Incorporation by Lif and Epr into Positions 3 and 5 of the Staphylococcal Peptidoglycan Interpeptide Bridge , 2000, Journal of bacteriology.

[76]  A. Carnicero,et al.  Purification and peptidase activity of a bacteriolytic extracellular enzyme from Pseudomonas aeruginosa. , 1989, Research in microbiology.

[77]  J. Borowski,et al.  Methicillin-resistant Staphylococci , 1964, Lancet.

[78]  Ry Young,et al.  The Pinholin of Lambdoid Phage 21: Control of Lysis by Membrane Depolarization , 2007, Journal of bacteriology.

[79]  C. Michiels,et al.  Food applications of bacterial cell wall hydrolases. , 2011, Current opinion in biotechnology.

[80]  Yun-Jaie Choi,et al.  Comparison of the Antibacterial Properties of Phage Endolysins SAL-1 and LysK , 2011, Antimicrobial Agents and Chemotherapy.

[81]  M. Artenstein,et al.  Systemic lysostaphin in man--apparent antimicrobial activity in a neutropenic patient. , 1974, The New England journal of medicine.

[82]  L. Heath,et al.  The lysostaphin endopeptidase resistance gene (epr) specifies modification of peptidoglycan cross bridges in Staphylococcus simulans and Staphylococcus aureus , 1995, Applied and environmental microbiology.

[83]  M. Marquart,et al.  The Effectiveness of Lysostaphin Therapy for Experimental Coagulase-Negative Staphylococcus Endophthalmitis , 2006, Current eye research.

[84]  W. Hryniewicz,et al.  Staphylococcus aureus biofilm as a target for single or repeated doses of oxacillin, vancomycin, linezolid and/or lysostaphin , 2008, Folia Microbiologica.

[85]  D. Donovan,et al.  Lysis of staphylococcal mastitis pathogens by bacteriophage phi11 endolysin. , 2006, FEMS microbiology letters.

[86]  G. Shockman Microbial peptidoglycan (murein) hydrolases , 1994 .

[87]  M. Grinholc,et al.  Alternative therapies in Staphylococcus aureus diseases. , 2012, Acta biochimica Polonica.

[88]  P. Coote,et al.  Bactericidal synergy of lysostaphin in combination with antimicrobial peptides , 2011, European Journal of Clinical Microbiology & Infectious Diseases.

[89]  A. Clarke,et al.  O-acetylated peptidoglycan: its occurrence, pathobiological significance, and biosynthesis. , 1992, Canadian journal of microbiology.

[90]  G. Doern,et al.  The Clinical Predictive Value (or Lack Thereof) of the Results of In Vitro Antimicrobial Susceptibility Tests , 2011, Journal of Clinical Microbiology.

[91]  D. Donovan,et al.  LysK CHAP endopeptidase domain is required for lysis of live staphylococcal cells. , 2009, FEMS microbiology letters.

[92]  M. Sugai,et al.  Purification and molecular characterization of glycylglycine endopeptidase produced by Staphylococcus capitis EPK1 , 1997, Journal of bacteriology.

[93]  D. Ohman,et al.  Secreted LasA of Pseudomonas aeruginosa is a staphylolytic protease. , 1993, The Journal of biological chemistry.

[94]  R. Jayaswal,et al.  Molecular cloning, sequencing, and expression of lytM, a unique autolytic gene of Staphylococcus aureus , 1997, Journal of bacteriology.

[95]  B. Martínez,et al.  Lytic activity of the recombinant staphylococcal bacteriophage PhiH5 endolysin active against Staphylococcus aureus in milk. , 2008, International journal of food microbiology.

[96]  B. Heniford,et al.  The addition of lysostaphin dramatically improves survival, protects porcine biomesh from infection, and improves graft tensile shear strength. , 2011, The Journal of surgical research.

[97]  S. Walsh,et al.  Improved Pharmacokinetics and Reduced Antibody Reactivity of Lysostaphin Conjugated to Polyethylene Glycol , 2003, Antimicrobial Agents and Chemotherapy.

[98]  A. Goglio,et al.  Methicillin-resistant Staphylococcus aureus: related infections and antibiotic resistance. , 2010, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[99]  Aidan Coffey,et al.  Phage Lysin LysK Can Be Truncated to Its CHAP Domain and Retain Lytic Activity against Live Antibiotic-Resistant Staphylococci , 2008, Applied and Environmental Microbiology.

[100]  E. Hume,et al.  Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit. , 2000, Investigative ophthalmology & visual science.

[101]  G. Ayliffe The progressive international spread of methicillin-resistant Staphylococcus aureus , 1997 .

[102]  W. Schaffner,et al.  Efficacy and safety of topical lysostaphin treatment of persistent nasal carriage of Staphylococcus aureus. , 1971, Applied microbiology.

[103]  J. Leiva,et al.  Antibiotic susceptibility assay for Staphylococcus aureus in biofilms developed in vitro. , 1999, The Journal of antimicrobial chemotherapy.

[104]  W. Zygmunt,et al.  Lysostaphin: model for a specific enzymatic approach to infectious disease. , 1972, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[105]  D. Ohman,et al.  A continuous spectrophotometric assay for Pseudomonas aeruginosa LasA protease (staphylolysin) using a two-stage enzymatic reaction. , 2004, Analytical biochemistry.

[106]  A. Friedrich,et al.  In Vitro Activity against Staphylococcus aureus of a Novel Antimicrobial Agent, PRF-119, a Recombinant Chimeric Bacteriophage Endolysin , 2011, Antimicrobial Agents and Chemotherapy.

[107]  W. Hammes,et al.  Stable Expression of the Lysostaphin Gene in Meat Lactobacilli by Introducing Deletions within the Prosequence , 1996 .

[108]  J. Weese,et al.  Methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius in veterinary medicine. , 2010, Veterinary microbiology.

[109]  K. Plaut,et al.  Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice , 2001, Nature Biotechnology.

[110]  G. Ayliffe The progressive intercontinental spread of methicillin-resistant Staphylococcus aureus. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[111]  D. Ohman,et al.  Elastase and the LasA Protease of Pseudomonas aeruginosa Are Secreted with Their Propeptides* , 1998, The Journal of Biological Chemistry.

[112]  Y. Prasad,et al.  P-27/HP Endolysin as Antibacterial Agent for Antibiotic Resistant Staphylococcus aureus of Human Infections , 2011, Current Microbiology.

[113]  Wang Di,et al.  Trichoderma spp. from rhizosphere soil and their antagonism against Fusarium sambucinum , 2012 .

[114]  F. Götz,et al.  Activity of the major staphylococcal autolysin Atl. , 2006, FEMS microbiology letters.

[115]  D. Ohman,et al.  A substitution at His-120 in the LasA protease of Pseudomonas aeruginosa blocks enzymatic activity without affecting propeptide processing or extracellular secretion , 1996, Journal of bacteriology.

[116]  Gabriele Bierbaum,et al.  Lytic Activity of Recombinant Bacteriophage φ11 and φ12 Endolysins on Whole Cells and Biofilms of Staphylococcus aureus , 2006, Applied and Environmental Microbiology.

[117]  D. Missiakas,et al.  Recurrent infections and immune evasion strategies of Staphylococcus aureus. , 2012, Current opinion in microbiology.

[118]  N. Klyachko,et al.  LysK, the enzyme lysing Staphylococcus aureus cells: specific kinetic features and approaches towards stabilization. , 2010, Biochimie.

[119]  P. A. Schad,et al.  Nucleotide sequence and expression in Escherichia coli of the Pseudomonas aeruginosa lasA gene , 1988, Journal of bacteriology.

[120]  C. Schindler,et al.  PURIFICATION AND PROPERTIES OF LYSOSTAPHIN--A LYTIC AGENT FOR STAPHYLOCOCCUS AUREUS. , 1965, Biochimica et biophysica acta.

[121]  Chad W. Euler,et al.  A Novel Chimeric Lysin Shows Superiority to Mupirocin for Skin Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains , 2010, Antimicrobial Agents and Chemotherapy.

[122]  A. Loeffler,et al.  Companion animals: a reservoir for methicillin-resistant Staphylococcus aureus in the community? , 2010, Epidemiology and Infection.

[123]  A. Pande,et al.  Cytoplasmic expression of mature glycylglycine endopeptidase lysostaphin with an amino terminal hexa-histidine in a soluble and catalytically active form in Escherichia coli. , 2006, Protein expression and purification.

[124]  K. Schleifer,et al.  Peptidoglycan Types of Bacterial Cell Walls and Their Taxonomic Implications , 1973, Bacteriological reviews.

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

[126]  P. Courvalin,et al.  VanA-Type Vancomycin-Resistant Staphylococcus aureus , 2009, Antimicrobial Agents and Chemotherapy.

[127]  G. Fitzgerald,et al.  The Recombinant Phage Lysin LysK Has a Broad Spectrum of Lytic Activity against Clinically Relevant Staphylococci, Including Methicillin-Resistant Staphylococcus aureus , 2005, Journal of bacteriology.

[128]  S. Shahsavan,et al.  Emergence of High-Level Vancomycin-Resistant Staphylococcus aureus in the Imam Khomeini Hospital in Tehran , 2008, Medical Principles and Practice.

[129]  W. Vollmer,et al.  Why are pathogenic staphylococci so lysozyme resistant? The peptidoglycan O‐acetyltransferase OatA is the major determinant for lysozyme resistance of Staphylococcus aureus , 2004, Molecular microbiology.

[130]  I. Lasa,et al.  Lysostaphin and clarithromycin: a promising combination for the eradication of Staphylococcus aureus biofilms. , 2011, International journal of antimicrobial agents.

[131]  M. Loessner,et al.  Bacteriophage endolysins--current state of research and applications. , 2005, Current opinion in microbiology.

[132]  J. Mond,et al.  Lysostaphin eradicates established Staphylococcus aureus biofilms in jugular vein catheterized mice. , 2009, The Journal of antimicrobial chemotherapy.

[133]  E. Smid,et al.  Optimization of the Lactococcus lactis nisin-controlled gene expression system NICE for industrial applications , 2005, Microbial cell factories.

[134]  G. Archer,et al.  Lysostaphin Treatment of Experimental Aortic Valve Endocarditis Caused by a Staphylococcus aureus Isolate with Reduced Susceptibility to Vancomycin , 1999, Antimicrobial Agents and Chemotherapy.

[135]  M. Bochtler,et al.  Anti-staphylococcal activities of lysostaphin and LytM catalytic domain , 2012, BMC Microbiology.

[136]  J. Synowiecki,et al.  PROTECTIVE EFFECT OF LYSOSTAPHIN FROM STAPHYLOCOCCUS SIMULANS AGAINST GROWTH OF STAPHYLOCOCCUS AUREUS IN MILK AND SOME OTHER FOOD PRODUCTS , 2007 .

[137]  F. Götz,et al.  Studies on prolysostaphin processing and characterization of the lysostaphin immunity factor (Lif) of Staphylococcus simulans biovar staphylolyticus , 1997, Molecular microbiology.

[138]  A. Tomasz,et al.  Altered muropeptide composition in Staphylococcus aureus strains with an inactivated femA locus , 1993, Journal of bacteriology.

[139]  O. Iversen,et al.  Studies on lysostaphin. Separation and characterization of three enzymes. , 1973, European journal of biochemistry.

[140]  G. Archer,et al.  Combinations of Lysostaphin with β-Lactams Are Synergistic against Oxacillin-Resistant Staphylococcus epidermidis , 2002, Antimicrobial Agents and Chemotherapy.

[141]  C. Weidenmaier,et al.  Influence of Wall Teichoic Acid on Lysozyme Resistance in Staphylococcus aureus , 2006, Journal of bacteriology.

[142]  W. Hryniewicz,et al.  Lysostaphin as a potential therapeutic agent for staphylococcal biofilm eradication. , 2005, Polish journal of microbiology.

[143]  R. Jayaswal,et al.  Characterization of a chromosomally encoded glycylglycine endopeptidase of Staphylococcus aureus. , 1999, Microbiology.