Why are pathogenic staphylococci so lysozyme resistant? The peptidoglycan O‐acetyltransferase OatA is the major determinant for lysozyme resistance of Staphylococcus aureus

Staphylococcus species belong to one of the few bacterial genera that are completely lysozyme resistant, which greatly contributes to their persistence and success in colonizing the skin and mucosal areas of humans and animals. In an attempt to discover the cause of lysozyme resistance, we identified a gene, oatA, in Staphylococcus aureus. The corresponding oatA deletion mutant had an increased sensitivity to lysozyme. HPLC and electrospray ionization tandem mass spectrometry analyses of the cell wall revealed that the muramic acid of peptidoglycan of the wild‐type strain was O‐acetylated at C6‐OH, whereas the muramic acid of the oatA mutant lacked this modification. The complemented oatA mutant was lysozyme resistant. We identified the first bacterial peptidoglycan‐specific O‐acetyltransferase in S. aureus and showed that OatA, an integral membrane protein, is the molecular basis for the high lysozyme resistance in staphylococci.

[1]  B. Neumeister,et al.  Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections , 2004, Nature Medicine.

[2]  O. Terenius,et al.  Parasite‐specific immune response in adult Drosophila melanogaster: a genomic study , 2004, EMBO reports.

[3]  H. Neumann,et al.  MprF-mediated biosynthesis of lysylphosphatidylglycerol, an important determinant in staphylococcal defensin resistance. , 2004, FEMS microbiology letters.

[4]  A. Labigne,et al.  Detailed Structural Analysis of the Peptidoglycan of the Human Pathogen Neisseria meningitidis* , 2003, Journal of Biological Chemistry.

[5]  V. Nizet,et al.  Alanylation of teichoic acids protects Staphylococcus aureus against Toll-like receptor 2-dependent host defense in a mouse tissue cage infection model. , 2003, The Journal of infectious diseases.

[6]  Å. Danielsson,et al.  Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis , 2003, Clinical and experimental immunology.

[7]  Kenneth K. Chan,et al.  Electrospray LC-MS/MS quantitation, stability, and preliminary pharmacokinetics of bradykinin antagonist polypeptide B201 (NSC 710295) in the mouse. , 2002, Journal of pharmaceutical and biomedical analysis.

[8]  A. Tarkowski,et al.  Staphylococcal peptidoglycans induce arthritis , 2001, Arthritis research.

[9]  S. Withers,et al.  Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate , 2001, Nature.

[10]  B. Cookson.  Whole genome sequencing of methicillin resistant Staphylococcus aureus , 2001 .

[11]  M. Kanehisa,et al.  Whole genome sequencing of meticillin-resistant Staphylococcus aureus , 2001, The Lancet.

[12]  Gina Pugliese,et al.  Nasal Carriage as a Source of Staphylococcus aureus Bacteremia , 2001, Infection Control & Hospital Epidemiology.

[13]  H Stammer,et al.  Nasal Carriage as a Source of Staphylococcus aureus Bacteremia , 2001 .

[14]  A. Tomasz,et al.  The pgdA Gene Encodes for a PeptidoglycanN-Acetylglucosamine Deacetylase in Streptococcus pneumoniae * , 2000, The Journal of Biological Chemistry.

[15]  H. Kalbacher,et al.  Inactivation of the dlt Operon inStaphylococcus aureus Confers Sensitivity to Defensins, Protegrins, and Other Antimicrobial Peptides* , 1999, The Journal of Biological Chemistry.

[16]  R. Brückner.  Gene replacement in Staphylococcus carnosus and Staphylococcus xylosus. , 1997, FEMS microbiology letters.

[17]  A. Clarke,et al.  Extent of peptidoglycan O acetylation in the tribe Proteeae , 1993, Journal of bacteriology.

[18]  A. Tomasz,et al.  Peptidoglycan composition in heterogeneous Tn551 mutants of a methicillin-resistant Staphylococcus aureus strain. , 1992, The Journal of biological chemistry.

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

[20]  S. Gordon,et al.  Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization , 1991, The Journal of experimental medicine.

[21]  A. Clarke,et al.  Evidence for N----O acetyl migration as the mechanism for O acetylation of peptidoglycan in Proteus mirabilis , 1991, Journal of bacteriology.

[22]  B. Glauner.  Separation and quantification of muropeptides with high-performance liquid chromatography. , 1988, Analytical biochemistry.

[23]  R. Losick,et al.  Genetic analysis of Bacillus subtilis spo mutations generated by Tn917-mediated insertional mutagenesis. , 1987, Genetics.

[24]  F. Götz,et al.  Improvements of protoplast transformation in Staphylococcus carnosus , 1987 .

[25]  H. Perkins,et al.  The peptidoglycan of Neisseria gonorrhoeae, with or without O-acetyl groups, contains anhydro-muramyl residues. , 1985, Journal of general microbiology.

[26]  H. H. Martin,et al.  Modification of peptidoglycan structure by penicillin action in cell walls of Proteus mirabilis. , 1979, European journal of biochemistry.

[27]  S. Iordanescu,et al.  Two restriction and modification systems in Staphylococcus aureus NCTC8325. , 1976, Journal of general microbiology.

[28]  K. Hayashi.  A rapid determination of sodium dodecyl sulfate with methylene blue. , 1975, Analytical biochemistry.

[29]  Y. Araki,et al.  Occurrence of N-nonsubstituted glucosamine residues in peptidoglycan of lysozyme-resistant cell walls from Bacillus cereus. , 1972, The Journal of biological chemistry.

[30]  J. Hash,et al.  The N,O-diacetylmuramidase of Chalaropsis species. I. Purification and crystallization. , 1967, The Journal of biological chemistry.

[31]  A. North,et al.  Crystallographic studies of the activity of hen egg-white lysozyme , 1967, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[32]  J. Strominger,et al.  Mechanisms of Enzymatic Bacteriolysis , 1967 .

[33]  J. Strominger,et al.  STRUCTURE OF THE CELL WALL OF STAPHYLOCOCCUS AUREUS, STRAIN COPENHAGEN. II. SEPARATION AND STRUCTURE OF DISACCHARIDES. , 1963, Biochemistry.

[34]  J. Strominger,et al.  STRUCTURE OF THE CELL WALL OF STAPHYLOCOCCUS AUREUS, STRAIN COPENHAGEN. I. PREPARATION OF FRAGMENTS BY ENZYMATIC HYDROLYSIS. , 1963, Biochemistry.

[35]  M. Mccarty,et al.  STUDIES ON THE CHEMICAL STRUCTURE OF THE STREPTOCOCCAL CELL WALL , 1961, The Journal of experimental medicine.

[36]  W. Brumfitt.  The mechanism of development of resistance to lysozyme by some gram-positive bacteria and its results. , 1959, British journal of experimental pathology.

[37]  A. Wardlaw,et al.  Development of Lysozyme-Resistance in Micrococcus Lysodiekticus and its Association With an Increased O-Acetyl Content of the Cell Wall , 1958, Nature.

[38]  A. Abrams.  O-acetyl groups in the cell wall of Streptococcus faecalis. , 1958, The Journal of biological chemistry.

[39]  S. Cramton,et al.  In vitro methods to study staphylococcal biofilm formation. , 2001, Methods in enzymology.

[40]  M. Wilm,et al.  Analytical properties of the nanoelectrospray ion source. , 1996, Analytical chemistry.

[41]  F. Götz,et al.  Transformation of Staphylococcus epidermidis and other staphylococcal species with plasmid DNA by electroporation. , 1990, FEMS microbiology letters.

[42]  K. Schleifer.  Chemical structure of the peptidoglycan, its modifiability and relation to the biological activity. , 1975, Zeitschrift fur Immunitatsforschung, experimentelle und klinische Immunologie.

[43]  J. Strominger,et al.  Mechanisms of enzymatic bacteriaolysis. Cell walls of bacteri are solubilized by action of either specific carbohydrases or specific peptidases. , 1967, Science.

[44]  D. F. Koenig,et al.  Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Angstrom resolution. , 1965, Nature.