The lipid-modifying multiple peptide resistance factor is an oligomer consisting of distinct interacting synthase and flippase subunits

mBio

Volumn 6, Issue 1, 2015, Pages

  Ernst, Christoph M ^a,b,c,d   Kuhn, Sebastian ^a,b   Slavetinsky, Christoph J ^a,b   Krismer, Bernhard ^a,b   Heilbronner, Simon ^a,b   Gekeler, Cordula ^a,b   Kraus, Dirk ^a,b   Wagner, Samuel ^a,b   Peschel, Andreas ^a,b  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b German Center for Research in Infectious Disease (DZIF)   (Germany)

^c HARVARD MEDICAL SCHOOL   (United States)

^d BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; AMINO ACID; ANTIINFECTIVE AGENT; BACTERIOCIN; DAPTOMYCIN; DEFENSIN; DIMER; FLIPPASE; LIPID; LYSINE; MEMBRANE PROTEIN; MULTIPLE PEPTIDE RESISTANCE FACTOR; OLIGOMER; PHOSPHATIDYLGLYCEROL; PHOSPHOLIPID; POLYPEPTIDE ANTIBIOTIC AGENT; PROLINE; SYNTHETASE; UNCLASSIFIED DRUG; AMINOACYLTRANSFERASE; BACTERIAL PROTEIN; MPRF PROTEIN, STAPHYLOCOCCUS AUREUS; PROTEIN SUBUNIT;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ANTIMICROBIAL THERAPY; ARCHAEON; ARTICLE; BACTERIAL MEMBRANE; CARBOXY TERMINAL SEQUENCE; CELLULAR SECRETION; COMMENSAL; CONTROLLED STUDY; COVALENT BOND; DRUG TARGETING; ENZYME ACTIVITY; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HOST CELL; INNATE IMMUNITY; LIPID COMPOSITION; MEMBRANE LEAFLET; MOLECULAR INTERACTION; NONHUMAN; OLIGOMERIZATION; PHOSPHOLIPID BILAYER; PHOSPHOLIPID SYNTHESIS; PHOSPHOLIPID TRANSFER; PRIORITY JOURNAL; PROKARYOTE; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN SUBUNIT; STAPHYLOCOCCUS AUREUS; SURFACE CHARGE; CELL MEMBRANE; CHEMISTRY; DIMERIZATION; DRUG EFFECTS; ENZYMOLOGY; GENETICS; HUMAN; METABOLISM; MICROBIOLOGY; PROTEIN TERTIARY STRUCTURE; STAPHYLOCOCCUS INFECTION; TRANSPORT AT THE CELLULAR LEVEL;

ARCHAEA; BACTERIA (MICROORGANISMS); EUKARYOTA; NEGIBACTERIA; POSIBACTERIA; PROKARYOTA; STAPHYLOCOCCUS AUREUS;

AMINOACYLTRANSFERASES; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; BIOLOGICAL TRANSPORT; CELL MEMBRANE; DIMERIZATION; HUMANS; PHOSPHOLIPIDS; PROTEIN STRUCTURE, TERTIARY; PROTEIN SUBUNITS; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS;

EID: 84924188257     PISSN: 21612129     EISSN: 21507511     Source Type: Journal    
DOI: 10.1128/mBio.02340-14     Document Type: Article

References (35)

1. Pomorski T, Menon AK. 2006. Lipid flippases and their biological functions. Cell Mol Life Sci 63: 2908-2921. http://dx. doi. org/10. 1007/s00018-006-6167-7.
2. Hancock RE, Sahl HG. 2006. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24: 1551-1557. http://dx. doi. org/10. 1038/nbt1267.
3. Peschel A, Sahl HG. 2006. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4: 529-536. http://dx. doi. org/10. 1038/nrmicro1441.
4. Wenzel M, Chiriac AI, Otto A, Zweytick D, May C, Schumacher C, Gust R, Albada HB, Penkova M, Krämer U, Erdmann R, Metzler-Nolte N, Straus SK, Bremer E, Becher D, Brötz-Oesterhelt H, Sahl HG, Bandow JE. 2014. Small cationic antimicrobial peptides delocalize peripheral membrane proteins. Proc Natl Acad Sci U S A 111: E1409-E1418. http://dx. doi. org/10. 1073/pnas. 1319900111.
5. Breukink E, Wiedemann I, van Kraaij C, Kuipers OP, Sahl HG, de Kruijff B. 1999. Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286: 2361-2364. http://dx. doi. org/10. 1126/science. 286. 5448. 2361.
6. Ernst CM, Staubitz P, Mishra NN, Yang SJ, Hornig G, Kalbacher H, Bayer AS, Kraus D, Peschel A. 2009. The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog 5: e1000660. http://dx. doi. org/10. 1371/journal. ppat. 1000660.
7. Jung D, Rozek A, Okon M, Hancock RE. 2004. Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomyc i n. Chem Biol 11: 949-957. http://dx. doi. org/10. 1016/j. chembiol. 2004. 04. 020.
8. Nishi H, Komatsuzawa H, Fujiwara T, McCallum N, Sugai M. 2004. Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus. Antimicrob Agents Chemother 48: 4800-4807. http://dx. doi. org/10. 1128/AAC. 48. 12. 4800-4807. 2004.
9. Tran TT, Panesso D, Mishra NN, Mileykovskaya E, Guan Z, Munita JM, Reyes J, Diaz L, Weinstock GM, Murray BE, Shamoo Y, Dowhan W, Bayer AS, Arias CA. 2013. Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids. mBio 4(4): e00281-13. http://dx. doi. org/10. 1128/mBio. 00281-13.
10. Ernst CM, Peschel A. 2011. Broad-spectrum antimicrobial peptide resistance by MprF-mediated aminoacylation and flipping of phospholipids. Mol Microbiol 80: 290-299. http://dx. doi. org/10. 1111/j. 1365-2958. 2011. 07576. x.
11. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A, van Kessel KP, van Strijp JA. 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine. J Exp Med 193: 1067-1076. http://dx. doi. org/10. 1084/jem. 193. 9. 1067.
12. Gunn JS. 2001. Bacterial modification of LPS and resistance to antimicrobial peptides. J Endotoxin Res 7: 57-62. http://dx. doi. org/10. 1177/09680519010070011001.
13. Arendt W, Hebecker S, Jäger S, Nimtz M, Moser J. 2012. Resistance phenotypes mediated by aminoacyl-phosphatidylglycerol synthases. J Bacteriol 194: 1401-1416. http://dx. doi. org/10. 1128/JB. 06576-11.
14. Roy H, Ibba M. 2009. Broad range amino acid specificity of RNA-dependent lipid remodeling by multiple peptide resistance factors. J Biol Chem 284: 29677-29683. http://dx. doi. org/10. 1074/jbc. M109. 046367.
15. Roy H, Ibba M. 2008. RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proc Natl Acad Sci U S A 105: 4667-4672. http://dx. doi. org/10. 1073/pnas. 0800006105.
16. Slavetinsky CJ, Peschel A, Ernst CM. 2012. Alanyl-phosphatidylglycerol and lysyl-phosphatidylglycerol are translocated by the same MprF flippases and have similar capacities to protect against the antibiotic daptomycin in Staphylococcus aureus. Antimicrob Agents Chemother 56: 3492-3497. http://dx. doi. org/10. 1128/AAC. 00370-12.
17. Bernsel A, Viklund H, Hennerdal A, Elofsson A. 2009. TOPCONS: consensus prediction of membrane protein topology. Nucleic Acids Res 37: W465-W468. http://dx. doi. org/10. 1093/nar/gkp363.
18. Viklund H, Elofsson A. 2008. OCTOPUS: improving topology prediction by two-track ANN-based preference scores and an extended topological grammar. Bioinformatics 24: 1662-1668. http://dx. doi. org/10. 1093/bioinformatics/btn221.
19. Haardt M, Bremer E. 1996. Use of phoA and lacZ fusions to study the membrane topology of ProW, a component of the osmoregulated ProU transport system of Escherichia coli. J Bacteriol 178: 5370-5381.
20. Thomas GH, Mullins JG, Merrick M. 2000. Membrane topology of the Mep/Amt family of ammonium transporters. Mol Microbiol 37: 331-344. http://dx. doi. org/10. 1046/j. 1365-2958. 2000. 01994. x.
21. van Geest M, Lolkema JS. 2000. Membrane topology and insertion of membrane proteins: search for topogenic signals. Microbiol Mol Biol Rev 64: 13-33. http://dx. doi. org/10. 1128/MMBR. 64. 1. 13-33. 2000.
22. Griffith KL, Wolf RE, Jr. 2002. Measuring beta-galactosidase activity in bacteria: cell growth, permeabilization, and enzyme assays in 96-well arrays. Biochem Biophys Res Commun 290: 397-402. http://dx. doi. org/10. 1006/bbrc. 2001. 6152.
23. Karimova G, Pidoux J, Ullmann A, Ladant D. 1998. A bacterial twohybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A 95: 5752-5756. http://dx. doi. org/10. 1073/pnas. 95. 10. 5752.
24. Heidler J, Strecker V, Csintalan F, Bleier L, Wittig I. 2013. Quantification of protein complexes by blue native electrophoresis. Methods Mol Biol 1033: 363-379. http://dx. doi. org/10. 1007/978-1-62703-487-6_23.
25. Schägger H, Cramer WA, von Jagow G. 1994. Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by twodimensional native electrophoresis. Anal Biochem 217: 220-230. http://dx. doi. org/10. 1006/abio. 1994. 1112.
26. Mishra NN, Yang SJ, Chen L, Muller C, Saleh-Mghir A, Kuhn S, Peschel A, Yeaman MR, Nast CC, Kreiswirth BN, Crémieux AC, Bayer AS. 2013. Emergence of daptomycin resistance in daptomycin-naive rabbits with methicillin-resistant Staphylococcus aureus prosthetic joint infection is associated with resistance to host defense cationic peptides and mprF polymorphisms. PLoS One 8: e71151. http://dx. doi. org/10. 1371/journal. pone. 0071151.
27. Sharom FJ. 2011. Flipping and flopping-lipids on the move. IUBMB Life 63: 736-746. http://dx. doi. org/10. 1002/iub. 515.
28. Manoil C. 1991. Analysis of membrane protein topology using alkaline phosphatase and beta-galactosidase gene fusions. Methods Cell Biol 34: 61-75.
29. Miller JH. 1972. Experiments in molecular genetics. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
30. Sarsero JP, Pittard AJ. 1995. Membrane topology analysis of Escherichia coli K-12 Mtr permease by alkaline phosphatase and beta-galactosidase fusions. J Bacteriol 177: 297-306.
31. Brückner R. 1992. A series of shuttle vectors for Bacillus subtilis and Escherichia coli. Gene 122: 187-192. http://dx. doi. org/10. 1016/0378-1119(92)90048-T.
32. Peschel A, Ottenwälder B, Götz F. 1996. Inducible production and cellular location of the epidermin biosynthetic enzyme EpiB using an improved staphylococcal expression system. FEMS Microbiol Lett 137: 279-284. http://dx. doi. org/10. 1111/j. 1574-6968. 1996. tb08119. x.
33. Bligh EG, Dyer WJ. 1959. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911-917. http://dx. doi. org/10. 1139/o59-099.
34. Wagner S, Königsmaier L, Lara-Tejero M, Lefebre M, Marlovits TC, Galán JE. 2010. Organization and coordinated assembly of the type III secretion export apparatus. Proc Natl Acad Sci U S A 107: 17745-17750. http://dx. doi. org/10. 1073/pnas. 1008053107.
35. Tse YM, Yu M, Tsang JS. 2009. Topological analysis of a haloacid permease of a Burkholderia sp. bacterium with a PhoA-LacZ reporter. BMC Microbiol 9: 233. http://dx. doi. org/10. 1186/1471-2180-9-233.