The giant protein ebh is a determinant of Staphylococcus aureus cell size and complement resistance

Journal of Bacteriology

Volumn 196, Issue 5, 2014, Pages 971-981

  Cheng, Alice G ^a,b   Missiakas, Dominique ^a   Schneewind, Olaf ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; BACTERIAL PROTEINS; CARRIER PROTEINS; COMPLEMENT SYSTEM PROTEINS; GENE EXPRESSION REGULATION, BACTERIAL; MICE; MUTATION; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS;

EID: 84893791748     PISSN: 00219193     EISSN: 10985530     Source Type: Journal    
DOI: 10.1128/JB.01366-13     Document Type: Article

References (88)

1. Lowy FD. 1998. Staphylococcus aureus infections. N. Engl. J. Med. 339: 520-532. http://dx.doi.org/10.1056/NEJM199808203390806.
2. DeLeo FR, Otto M, Kreiswirth BN, Chambers HF. 2010. Community-associated meticillin-resistant Staphylococcus aureus. Lancet 375:1557-1568. http://dx.doi.org/10.1016/S0140-6736(09)61999-1.
3. Klevens RM, Edwards JR, Gaynes RP. 2008. The impact of antimicrobial-resistant, health care-associated infections on mortality in the United States. Clin. Infect. Dis. 47:927-930. http://dx.doi.org/10.1086/591698.
4. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK. 2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:1763-1771. http://dx.doi.org/10.1001/jama.298.15.1763.
5. Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI. 2004. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin. Infect. Dis. 38:1673-1681. http://dx .doi.org/10.1086/420818.
6. Stevens DH, Herr D, Campiris H, Hunt JL, Batts DH, Hafkin B. 2002. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin. Infect. Dis. 34:1481-1490. http://dx .doi.org/10.1086/340353.
7. van Hal SJ, Paterson DL. 2011. New Gram-positive antibiotics: better than vancomycin? Curr. Opin. Infect. Dis. 24:515-520. http://dx.doi.org /10.1097/QCO.0b013e32834ab1de.
8. Giesbrecht P, Kersten T, Maidhof H, Wecke J. 1998. Staphylococcal cell wall: morphogenesis and fatal variations in the presence ofpenicillin. Microbiol. Mol. Biol. Rev. 62:1371-1414.
9. TzagoloffH, Novick R. 1977. Geometry of cell division in Staphylococcus aureus. J. Bacteriol. 129:343-350.
10. Frankel MB, Hendrickx AP, Missiakas DM, Schneewind O. 2011. LytN, a murein hydrolase in the cross-wall compartment of Staphylococcus aureus, is involved in proper bacterial growth and envelope assembly. J. Biol. Chem. 286:32593-32605. http://dx.doi.org/10.1074/jbc.M111.258863.
11. DeDent AC, McAdow M, Schneewind O. 2007. Distribution ofprotein A on the surface ofStaphylococcus aureus. J. Bacteriol. 189:4473-4484. http: //dx.doi.org/10.1128/JB.00227-07.
12. DeDent AC, Missiakas DM, Schneewind O. 2008. Signal peptides direct surface proteins to two distinct envelope locations of Staphylococcus aureus. EMBO J. 27:2656-2668. http://dx.doi.org/10.1038/emboj.2008.185.
13. Frankel MB, Schneewind O. 2012. Determinants of murein hydrolase targeting to cross-wall of Staphylococcus aureus peptidoglycan. J. Biol. Chem. 287:10460-10471. http://dx.doi.org/10.1074/jbc.M111.336404.
14. Yu W, Gotz F. 2012. Cell wall antibiotics provoke accumulation of anchored mCherry in the cross wall of Staphylococcus aureus. PLoS One 7:e30076. http://dx.doi.org/10.1371/journal.pone.0030076.
15. Schneewind O, Missiakas DM. 2012. Protein secretion and surface display in Gram-positive bacteria. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367:1123-1139. http://dx.doi.org/10.1098/rstb.2011.0210.
16. Clarke SR, Harris LG, Richards RG, Foster SJ. 2002. Analysis of Ebh, a 1.1-megadalton cell wall-associated fibronectin-binding protein of Staphylococcus aureus. Infect. Immun. 70:6680-6687. http://dx.doi.org/10 .1128/IAI.70.12.6680-6687.2002.
17. Bae T, Schneewind O. 2003. The YSIRK-G/S motif of staphylococcal protein A and its role in efficiency of signal peptide processing. J. Bacteriol. 185:2910-2919. http://dx.doi.org/10.1128/JB.185.9.2910-2919.2003.
18. Williams RJ, Henderson B, Sharp LJ, Nair SP. 2002. Identification of a fibronec-tin-binding protein from Staphylococcus epidermidis. Infect. Immun. 70: 6805-6810. http://dx.doi.org/10.1128/IAI.70.12.6805-6810.2002.
19. Christner M, Franke GC, Schommer NN, Wendt U, Wegert K, Pehle P, Kroll G, Schulze C, Buck F, Mack D, Aepfelbacher M, Rohde H. 2010. The giant extracellular matrix-binding protein of Staphylococcus epidermidis mediates biofilm accumulation and attachment to fibronectin. Mol. Microbiol. 75:187-207. http://dx.doi.org/10.1111/j.1365-2958.2009.06981.x.
20. McCarthy AJ, Lindsay JA. 2010. Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host-pathogen interactions. BMC Microbiol. 10: 173. http://dx.doi.org/10.1186/1471-2180-10-173.
21. Ben Zakour NL, Beatson SA, van den Broek AH, Thoday KL, Fitzgerald JR. 2012. Comparative genomics ofthe Staphylococcus intermedius group ofanimal pathogens. Front. Cell. Infect. Microbiol. 2:44. http://dx.doi.org /10.3389/fcimb.2012.00044.
22. Heilbronner S, Holden MT, van Tonder A, Geoghegan JA, Foster TJ, Parkhill J, Bentley SD. 2011. Genome sequence of Staphylococcus lugdunensis N920143 allows identification ofputative colonization and virulence factors. FEMS Microbiol. Lett. 322:60-67. http://dx.doi.org/10 .1111/j.1574-6968.2011.02339.x.
23. Kuroda M, Tanaka Y, Aoki R, Shu D, Tsumoto K, Ohta T. 2008. Staphylococcus aureus giant protein Ebh is involved in tolerance to transient hyperosmotic pressure. Biochem. Biophys. Res. Commun. 374:237-241. http://dx.doi.org/10.1016/j.bbrc.2008.07.037.
24. Tanaka Y, Sakamoto S, Kuroda M, Goda S, Gao Y, Tsumoto K, Hiragi Y, Yao M, Watanabe N, Ohta T, Tanaka I. 2008. A helical string of alternately connected three-helix bundles for the cell wall-associated adhesion protein Ebh from Staphylococcus aureus. Structure 16:488-496. http://dx.doi.org/10.1016/j.str.2007.12.018.
25. Kennedy AD, Otto M, Braughton KR, Whitney AR, Chen L, Mathema B, Mediavilla JR, Byrne KA, Parkins LD, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR. 2008. Epidemic community-associated methicil-lin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Proc. Natl. Acad. Sci. U. S. A. 105:1327-1332. http://dx.doi.org/10 .1073/pnas.0710217105.
26. Baba T, Bae T, Schneewind O, Takeuchi F, Hiramatsu K. 2008. Genome sequence of Staphylococcus aureus strain Newman and comparative analysis of staphylococcal genomes: polymorphism and evolution of two major pathogenicity islands. J. Bacteriol. 190:300-310. http://dx.doi.org/10 .1128/JB.01000-07.
27. Gill SR, Fouts DE, Archer GL, Mongodin EF, Deboy RT, Ravel J, Paulsen IT, Kolonay JF, Brinkac L, Beanan M, Dodson RJ, Daugherty SC, Madupu R, Angiuoli SV, Durkin AS, Haft DH, Vamathevan J, Khouri H, Utterback T, Lee C, Dimitrov G, Jiang L, Qin H, Weidman J, Tran K, Kang K, Hance IR, Nelson KE, Fraser CM. 2005. Insights on evolution ofvirulence and resistance from the completegenomeanalysisofanearlymethicillin-resistantStaphylococcusaureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain.J. Bacteriol. 187:2426-2438. http://dx.doi.org/10.1128/JB .187.7.2426-2438.2005.
28. Bæk KT, Frees D, Renzoni A, Barras C, Rodriguez N, Manzano C, Kelley WL. 2013. Genetic variation in the Staphylococcus aureus 8325 strain lineage revealed bywhole-genome sequencing. PLoS One 8:e77122. http://dx.doi.org/10.1371/journal.pone.0077122.
29. Sakamoto S, Tanaka Y, Tanaka I, Takei T, Yu J, Kuroda M, Yao M, Ohta T, Tsumoto K. 2008. Electron microscopy and computational studies ofEbh, a giant cell-wall-associated protein from Staphylococcus aureus. Biochem. Biophys. Res. Commun. 376:261-266. http://dx.doi.org/10 .1016/j.bbrc.2008.08.117.
30. Bae T, Banger AK, Wallace A, Glass EM, Aslund F, Schneewind O, Missiakas DM. 2004. Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing. Proc. Natl. Acad. Sci. U. S. A. 101:12312-12317. http://dx.doi.org/10.1073/pnas.0404728101.
31. Bae T, Schneewind O. 2006. Allelic replacement in Staphylococcus aureus with inducible counter-selection. Plasmid 55:58-63. http://dx.doi.org/10 .1016/j.plasmid.2005.05.005.
32. Frankel MB, Wojcik BM, DeDent AC, Missiakas DM, Schneewind O. 2010. ABI-domain containing proteins contribute to surface protein display and cell division in Staphylococcus aureus. Mol. Microbiol. 78:238-252. http://dx.doi.org/10.1111/j.1365-2958.2010.07334.x.
33. Studier FW, Rosenberg AH, Dunn JJ, Dubendorff JW. 1990. Use of T7 polymerase to direct expression of cloned genes. Methods Enzymol. 185: 60-89.
34. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, Lin F, Lin J, Carleton HA, Mongodin EF, Sensabaugh GF, Perdreau-Remington F. 2006. Complete genome sequence ofUSA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367:731-739. http://dx.doi.org/10.1016/S0140-6736(06)68231-7.
35. Grundling A, Schneewind O. 2007. Synthesis of glycerol phosphate lipoteichoic acid in Staphylococcus aureus. Proc. Natl. Acad. Sci. U. S. A. 104: 8478-8483. http://dx.doi.org/10.1073/pnas.0701821104.
36. Beck WD, Berger-Bachi B, Kayser FH. 1986. Additional DNA in methicillin-resistant Staphylococcus aureus and molecular cloning of mecspecific DNA. J. Bacteriol. 165:373-378.
37. Ubukata K, Nonoguchi R, Matsuhashi M, Konno M. 1989. Expression and inducibility in Staphylococcus aureus ofthe mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein. J. Bacteriol. 171:2882-2885.
38. Kim HK, Cheng AG, Kim H-Y, Missiakas DM, Schneewind O. 2010. Non-toxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections. J. Exp. Med. 207:1863-1870. http://dx.doi.org/10.1084 /jem.20092514.
39. Thammavongsa V, Kern JW, Missiakas DM, Schneewind O. 2009. Staphylococcus aureus synthesizes adenosine to escape host immune responses. J. Exp. Med. 206:2417-2427. http://dx.doi.org/10.1084/jem.20090097.
40. Gros P, Milder FJ, Janssen BJ. 2008. Complement driven by conformational changes. Nat. Rev. Immunol. 8:48-58. http://dx.doi.org/10.1038 /nri2231.
41. Laarman A, Milder F, van Strijp JA, Rooijakkers SH. 2010. Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications. J. Mol. Med. 88:115-120. http://dx.doi.org/10.1007 /s00109-009-0572-y.
42. Jongerius I, Kohl J, Pandey MK, Ruyken M, van Kessel KPM, van Strijp JAG, Rooijakkers SHM. 2007. Staphylococcal complement evasion by various convertase-blocking molecules. J. Exp. Med. 204:2461-2471. http: //dx.doi.org/10.1084/jem.20070818.
43. Rooijakkers SH, van Wamel WJ, Ruyken M, van Kessel KP, van Strijp JA. 2005. Anti-opsonic properties of staphylokinase. Microbes Infect. 7:476-484. http://dx.doi.org/10.1016/j.micinf.2004.12.014.
44. Rooijakkers SHM, Wu J, Ruyken M, van Domselaar R, Planken KL, TZekou A, Ricklin D, Lambris JD, Janssen BJC, van Strijp JAG, Gros P. 2009. Structural and functional implications of the alternative comple-ment pathway C3 convertase stabilized by a staphylococcal inhibitor. Nat. Immunol. 7:721-727. http://dx.doi.org/10.1038/ni.1756.
45. Harraghy N, Hussain M, Haggar A, Chavakis T, Sinha B, Herrmann M, Flock JI. 2003. The adhesive and immunomodulating properties of the multifunctional Staphylococcus aureus protein Eap. Microbiology 149: 2701-2707. http://dx.doi.org/10.1099/mic.0.26465-0.
46. Lee LY, Liang X, Hook M, Brown EL. 2004. Identification and charac-terization ofthe C3 binding domain ofthe Staphylococcus aureus extracellular fibrinogen-binding protein (Efb). J. Biol. Chem. 279:50710-50716. http://dx.doi.org/10.1074/jbc.M408570200.
47. Hammel M, Sfyroera G, Ricklin D, Magotti P, Lambris JD, Geisbrecht BV. 2007. A structural basis for complement inhibition by Staphylococcus aureus. Nat. Immunol. 8:430-437. http://dx.doi.org/10.1038/ni1450.
48. Anderson M, Chen YH, Butler EK, Missiakas DM. 2011. EsaD, a secretion factor for the Ess pathway in Staphylococcus aureus. J. Bacteriol. 193: 1583-1589. http://dx.doi.org/10.1128/JB.01096-10.
49. Mann PA, Muller A, Xiao L, Pereira PM, Yang C, Ho Lee S, Wang H, Trzeciak J, Schneeweis J, Dos Santos MM, Murgolo N, She X, Gill C, Balibar CJ, Labroli M, Su J, Flattery A, Sherborne B, Maier R, Tan CM, Black T, Onder K, Kargman S, Monsma FJJ, Pinho MG, Schneider T, Roemer T. 2013. Murgocil is a highly bioactive staphylococcal-specific inhibitor of the peptidoglycan glycosyltransferase enzyme MurG. ACS Chem. Biol. 8:2442-2451. http://dx.doi.org/10.1021/cb400487f.
50. Pereira SFF, Henriques AO, Pinho MG, de Lencastre H, Tomasz A. 2007. Role of PBP1 in cell division of Staphylococcus aureus. J. Bacteriol. 189:3525-3531. http://dx.doi.org/10.1128/JB.00044-07.
51. Leski TA, TomaszA. 2005. Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. J. Bacteriol. 187:1815-1824. http://dx.doi.org/10.1128/JB.187.5 .1815-1824.2005.
52. Pinho MG, Errington J. 2005. Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates. Mol. Microbiol. 55:799-807. http://dx.doi .org/10.1111/j.1365-2958.2004.04420.x.
53. Atilano ML, Pereira PM, Yates J, Reed P, Veiga H, Pinho M, Filipe SR. 2010. Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus. Proc. Natl. Acad. Sci. U. S. A. 107: 18991-18996. http://dx.doi.org/10.1073/pnas.1004304107.
54. Pinho MG, Errington J. 2003. Dispersed mode of Staphylococcus aureus cell wall synthesis in the absence of the division machinery. Mol. Microbiol. 50:871-881. http://dx.doi.org/10.1046/j.1365-2958.2003.03719.x.
55. Lovering AL, de Castro LH, Lim D, Strynadka NC. 2007. Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis. Science 315:1402-1405. http://dx.doi.org/10.1126/science.1136611.
56. Lovering AL, Safadi SS, Strynadka NC. 2012. Structural perspective of peptidoglycan biosynthesis and assembly. Annu. Rev. Biochem. 81:451-478. http://dx.doi.org/10.1146/annurev-biochem-061809-112742.
57. de Jonge BLM, Chang YS, Gage D, Tomasz A. 1992. Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. J. Biol. Chem. 267:11248-11254.
58. de Jonge BLM, Chang YS, Gage D, Tomasz A. 1992. Peptidoglycan composition in heterogeneous Tn551 mutants of a methicillin-resistant Staphylococcus aureus strain. J. Biol. Chem. 267:11255-11259.
59. Perry AM, Ton-That H, Mazmanian SK, Schneewind O. 2002. Anchoring of surface proteins to the cell wall of Staphylococcus aureus. III. Lipid II is an in vivo peptidoglycan substrate for sortase-catalyzed surface protein anchoring. J. Biol. Chem. 277:16241-16248. http://dx.doi.org/10.1074 /jbc.M109194200.
60. Raz A, Fischetti VA. 2008. Sortase A localizes to distinct foci on the Streptococcus pyogenes membrane. Proc. Natl. Acad. Sci. U. S. A. 105: 18549-18554. http://dx.doi.org/10.1073/pnas.0808301105.
61. Chung BC, Zhao J, Gillespie RA, Kwon DY, Guan Z, Hong J, Zhou P, Lee SY. 2013. Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. Science 341:1012-1016. http://dx.doi.org /10.1126/science.1236501.
62. Campbell J, Singh AK, Santa Maria JPJ, Kim Y, Brown S, Swoboda JG, Mylonakis E, Wilkinson BJ, Walker S. 2011. Synthetic lethal compound combinations reveal a fundamental connection between wall teichoic acid and peptidoglycan biosyntheses in Staphylococcus aureus. ACS Chem. Biol. 6:106-116. http://dx.doi.org/10.1021/cb100269f.
63. Brown S, Zhang YH, Walker S. 2008. A revised pathway proposed for Staphylococcus aureus wall teichoic acid biosynthesis based on in vitro reconstitution of the intracellular steps. Chem. Biol. 15:12-21. http://dx.doi .org/10.1016/j.chembiol.2007.11.011.
64. Xia G, Peschel A. 2008. Toward the pathway of S. aureus WTA biosynthesis. Chem. Biol. 15:95-96. http://dx.doi.org/10.1016/j.chembiol.2008 .02.005.
65. Chan YGY, Frankel MB, Dengler V, Schneewind O, Missiakas DM. 2013. Staphylococcus aureus mutants lacking the LytR-CpsA-Psr (LCP) family of enzymes release wall teichoic acids into the extracellular medium. J. Bacteriol. 195:4650-4659. http://dx.doi.org/10.1128/JB.00544-13.
66. Kawai Y, Marles-Wright J, Cleverley RM, Emmins R, Ishikawa S, Kuwano M, Heinz N, Bui NK, Hoyland CN, Ogasawara N, Lewis RJ, Vollmer W, Daniel RA, Errington J. 2011. A widespread family of bacterial cell wall assembly proteins. EMBO J. 30:4931-4941. http://dx.doi .org/10.1038/emboj.2011.358.
67. D'Elia MA, Pereira MP, Chung YS, Zhao W, Chau A, Kenney TJ, Sulavik MC, Black TA, Brown ED. 2006. Lesions in teichoic acid biosynthesis in Staphylococcus aureus lead to a lethal gain of function in the otherwise dispensable pathway. J. Bacteriol. 188:4183-4189. http://dx.doi .org/10.1128/JB.00197-06.
68. Weidenmaier C, Kokai-Kun JF, Kristian SA, Chanturiya T, Kalbacher H, Gross M, Nicholson G, Neumeister B, Mond JJ, Peschel A. 2004. Role ofteichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat. Med. 10:243-245. http://dx.doi .org/10.1038/nm991.
69. Hancock IC, Wiseman G, Baddiley J. 1976. Biosynthesis of the unit that links teichoic acid to the bacterial wall: inhibition by tunicamycin. FEBS Lett. 69:75-80. http://dx.doi.org/10.1016/0014-5793(76)80657-6.
70. Soldo B, Lazarevic V, Karamata D. 2002. tagO is involved in the synthesis of all anionic cell-wall polymers in Bacillus subtilis 168. Microbiology 148:2079-2087. http://mic.sgmjournals.org/content/148/7/2079 .full.pdf+html.
71. Farha MA, Leung A, Sewell EW, D'Elia MA, Allison SE, Ejim L, Pereira PM, Pinho MG, Wright GD, Brown ED. 2013. Inhibition of WTA synthesis blocks the cooperative action of PBPs and sensitizes MRSA to p-lactams. ACS Chem. Biol. 8:226-233. http://dx.doi.org/10.1021/cb300413m.
72. Bi EF, Lutkenhaus J. 1991. FtsZ ring structure associated with division in Escherichia coli. Nature 354:161-164. http://dx.doi.org/10.1038/354161a0.
73. Adams DW, Errington J. 2009. Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nat. Rev. Microbiol. 7:642-653. http: //dx.doi.org/10.1038/nrmicro2198.
74. Levin PA, Schwartz RL, Grossman AD. 1999. Identification and characterization ofa negative regulator ofFtsZ ring formation in Bacillus subtilis. Proc. Natl. Acad. Sci. U. S. A. 96:9642-9647. http://dx.doi.org/10.1073 /pnas.96.17.9642.
75. Jorge AM, Hoiczyk E, Gomes JP, Pinho MG. 2011. EzrA contributes to the regulation of cell size in Staphylococcus aureus. PLoS One 6:e27542. http://dx.doi.org/10.1371/journal.pone.0027542.
76. Hadders MA, Beringer DX, Gros P. 2007. Structure of C8alpha-MACPF reveals mechanism ofmembrane attack in complement immune defense. Science 317:1552-1554. http://dx.doi.org/10.1126/science.1147103.
77. Podack ER. 2009. How to polymerize in order to survive. Immunity 30:668-670. http://dx.doi.org/10.1016/j.immuni.2009.04.004.
78. Berger-Bachi B, Rohrer S. 2002. Factors influencing methicillin resis-tance in staphylococci. Arch. Microbiol. 178:165-171. http://dx.doi.org /10.1007/s00203-002-0436-0.
79. Utsui Y, Yokota T. 1985. Role of an altered penicillin binding protein in methicillinandcephem-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 28:397-403. http://dx.doi.org/10.1128/AAC.28.3.397.
80. Pinho MG, Filipe SR, De Lencastre H, Tomasz A. 2001. Complemen-tation ofthe essential peptidoglycan transpeptidase function ofpenicillin-binding protein 2 (PBP2) by the drug resistance protein PBP2A in Staphylococcus aureus. J. Bacteriol. 183:6525-6531. http://dx.doi.org/10.1128 /JB.183.22.6525-6531.2001.
81. Henze U, Sidow T, Wecke J, Labischinski H, Berger-Bachi B. 1993. Influence offemB on methicillin resistance and peptidoglycan metabolism in Staphylococcus aureus. J. Bacteriol. 175:1612-1620.
82. Rohrer S, Ehlert K, Tschierske M, Labischinski H, Berger-Bachi B. 1999. The essential Staphylococcus aureus gene fmhB is involved in the first step of peptidoglycan pentaglycine interpeptide formation. Proc. Natl. Acad. Sci. U. S. A. 96:9351-9356. http://dx.doi.org/10.1073/pnas.96.16.9351.
83. Ornelas-Soares A, de Lencastre H, de Jonge BLM, Tomasz A. 1994. Reduced methicillin resistance in a new Staphylococcus aureus transposon mutant that incorporates muramyl dipeptides into the cell wall peptidoglycan. J. Biol. Chem. 269:27246-27250.
84. Gustafson J, Strassle A, Hachler H, Kayser FH, Berger-Bachi B. 1994. The femC locus of Staphylococcus aureus required for methicillin resistance includes the glutamine synthetase operon. J. Bacteriol. 176:1460-1467.
85. Jolly L, Wu S, van Heijenoort J, de Lencastre H, Mengin-Lecreulx D, Tomasz A. 1997. The femR315 gene from Staphylococcus aureus, the interruption of which results in reduced methicillin resistance, encodes a phosphoglucosamine mutase. J. Bacteriol. 179:5321-5325.
86. Komatsuzawa H, Ohta K, Sugai M, Fujiwara T, Glanzmann P, Berger-Bachi B, Suginaka H. 2000. Tn551-mediated insertional inactivation of the fmtB gene encoding a cell wall-associated protein abolishes methicillin resistance in Staphylococcus aureus. J. Antimicrob. Chemother. 45:421-431. http://dx.doi.org/10.1093/jac/45.4.421.
87. Komatsuzawa H, Ohta K, Labischinski H, Sugai M, Suginaka H. 1999. Characterization offmtA, a gene that modulates the expression ofmethicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 43:2121-2125.
88. Komatsuzawa H, Ohta K, Fujiwara T, Choi GH, Labischinski H, Sugai M. 2001. Cloning and sequencing of the gene, fmtC, which affects oxacillin resistance in methicillin-resistant Staphylococcus au-reus. FEMS Microbiol. Lett. 203:49-54. http://dx.doi.org/10.1111/j.1574-6968.2001.tb10819.x.