Peptidoglycan associated lipoprotein (Pal) of (E. coli) is a characteristic bacterial lipoprotein, with an N-terminal lipid moiety anchoring it to the outer membrane. Since its discovery over three decades ago, Pal has been well studied for its participation in the Tol–Pal complex which spans the periplasm and has been proposed to play important roles in bacterial survival, pathogenesis and virulence. Previous studies of Pal place the lipoprotein in the periplasm of , allowing it to interact with Tol proteins and the peptidoglycan layer. Here, we describe for the first time, a subpopulation of Pal which is present on the cell surface of . Flow cytometry and confocal microscopy detect anti-Pal antibodies on the surface of intact cells. Interestingly, Pal is surface exposed in an ‘all or nothing’ manner, such that most of the cells contain only internal Pal, with fewer cells ( < 20  %) exhibiting surface Pal.


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  1. Abergel C., Bouveret E., Claverie J. M., Brown K., Rigal A., Lazdunski C., Bénédetti H. (1999). Structure of the Escherichia coli TolB protein determined by MAD methods at 1.95 A resolution. Structure 7, 12911300 [View Article][PubMed] [Google Scholar]
  2. Bernadac A., Gavioli M., Lazzaroni J. C., Raina S., Lloubès R. (1998). Escherichia coli tol-pal mutants form outer membrane vesicles. J Bacteriol 180, 48724878[PubMed] [Google Scholar]
  3. Bouveret E., Derouiche R., Rigal A., Lloubès R., Lazdunski C., Bénédetti H. (1995). Peptidoglycan-associated lipoprotein-TolB interaction. A possible key to explaining the formation of contact sites between the inner and outer membranes of Escherichia coli . J Biol Chem 270, 1107111077 [View Article][PubMed] [Google Scholar]
  4. Bouveret E., Bénédetti H., Rigal A., Loret E., Lazdunski C. (1999). In vitro characterization of peptidoglycan-associated lipoprotein (PAL)-peptidoglycan and PAL-TolB interactions. J Bacteriol 181, 63066311[PubMed] [Google Scholar]
  5. Braun V., Bosch V. (1972). Sequence of the murein-lipoprotein and the attachment site of the lipid. Eur J Biochem 28, 5169 [View Article][PubMed] [Google Scholar]
  6. Braun V., Rehn K. (1969). Chemical characterization, spatial distribution and function of a lipoprotein (murein-lipoprotein) of the E. coli cell wall. The specific effect of trypsin on the membrane structure. Eur J Biochem 10, 426438 [View Article][PubMed] [Google Scholar]
  7. Cascales E., Lloubès R. (2004). Deletion analyses of the peptidoglycan-associated lipoprotein Pal reveals three independent binding sequences including a TolA box. Mol Microbiol 51, 873885 [View Article][PubMed] [Google Scholar]
  8. Cascales E., Gavioli M., Sturgis J. N., Lloubès R. (2000). Proton motive force drives the interaction of the inner membrane TolA and outer membrane pal proteins in Escherichia coli . Mol Microbiol 38, 904915 [View Article][PubMed] [Google Scholar]
  9. Cascales E., Bernadac A., Gavioli M., Lazzaroni J. -C., Lloubès R. (2002). Pal lipoprotein of Escherichia coli plays a major role in outer membrane integrity. J Bacteriol 184, 754759 [View Article][PubMed] [Google Scholar]
  10. Clavel T., Germon P., Vianney A., Portalier R., Lazzaroni J. C. (1998). TolB protein of Escherichia coli K-12 interacts with the outer membrane peptidoglycan-associated proteins Pal, Lpp and OmpA. Mol Microbiol 29, 359367 [View Article][PubMed] [Google Scholar]
  11. Cowles C. E., Li Y., Semmelhack M. F., Cristea I. M., Silhavy T. J. (2011). The free and bound forms of Lpp occupy distinct subcellular locations in Escherichia coli . Mol Microbiol 79, 11681181 [View Article][PubMed] [Google Scholar]
  12. Deprez C., Lloubès R., Gavioli M., Marion D., Guerlesquin F., Blanchard L. (2005). Solution structure of the E. coli TolA C-terminal domain reveals conformational changes upon binding to the phage g3p N-terminal domain. J Mol Biol 346, 10471057 [View Article][PubMed] [Google Scholar]
  13. Gerding M. A., Ogata Y., Pecora N. D., Niki H., de Boer P. A. (2007). The trans-envelope Tol-Pal complex is part of the cell division machinery and required for proper outer-membrane invagination during cell constriction in E. coli . Mol Microbiol 63, 10081025 [View Article][PubMed] [Google Scholar]
  14. Godlewska R., Wiśniewska K., Pietras Z., Jagusztyn-Krynicka E. K. (2009). Peptidoglycan-associated lipoprotein (Pal) of Gram-negative bacteria: function, structure, role in pathogenesis and potential application in immunoprophylaxis. FEMS Microbiol Lett 298, 111 [View Article][PubMed] [Google Scholar]
  15. Hellman J., Zanzot E. M., Loiselle P. M., Amato S. F., Black K. M., Ge Y., Kurnick J. T., Warren H. S. (1997). Antiserum against Escherichia coli J5 contains antibodies reactive with outer membrane proteins of heterologous gram-negative bacteria. J Infect Dis 176, 12601268 [View Article][PubMed] [Google Scholar]
  16. Hellman J., Loiselle P. M., Tehan M. M., Allaire J. E., Boyle L. A., Kurnick J. T., Andrews D. M. (2000). Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum. Infect Immun 68, 25662572 [View Article][PubMed] [Google Scholar]
  17. Hellman J., Roberts J. D. Jr, Tehan M. M., Allaire J. E., Warren H. S. (2002). Bacterial peptidoglycan-associated lipoprotein is released into the bloodstream in gram-negative sepsis and causes inflammation and death in mice. J Biol Chem 277, 1427414280 [View Article][PubMed] [Google Scholar]
  18. Lazzaroni J. C., Portalier R. (1992). The excC gene of Escherichia coli K-12 required for cell envelope integrity encodes the peptidoglycan-associated lipoprotein (PAL). Mol Microbiol 6, 735742 [View Article][PubMed] [Google Scholar]
  19. Leduc M., Ishidate K., Shakibai N., Rothfield L. (1992). Interactions of Escherichia coli membrane lipoproteins with the murein sacculus. J Bacteriol 174, 79827988[PubMed] [Google Scholar]
  20. Lei H., Velez G., Kazlauskas A. (2011). Pathological signaling via platelet-derived growth factor receptor alpha involves chronic activation of Akt and suppression of p53. Mol Cell Biol 31, 17881799 [View Article][PubMed] [Google Scholar]
  21. Liang M. D., Bagchi A., Warren H. S., Tehan M. M., Trigilio J. A., Beasley-Topliffe L. K., Tesini B. L., Lazzaroni J. C., Fenton M. J., Hellman J. (2005). Bacterial peptidoglycan-associated lipoprotein: a naturally occurring toll-like receptor 2 agonist that is shed into serum and has synergy with lipopolysaccharide. J Infect Dis 191, 939948 [View Article][PubMed] [Google Scholar]
  22. Michel L. V., Snyder J., Schmidt R., Milillo J., Grimaldi K., Kalmeta B., Khan M. N., Sharma S., Wright L. K., Pichichero M. E. (2013). Dual orientation of the outer membrane lipoprotein P6 of nontypeable Haemophilus influenzae . J Bacteriol 195, 32523259 [View Article][PubMed] [Google Scholar]
  23. Mizuno T. (1981). A novel peptidoglycan-associated lipoprotein (PAL) found in the outer membrane of Proteus mirabilis and other Gram-negative bacteria. J Biochem 89, 10391049[PubMed] [Google Scholar]
  24. Narita S., Tokuda H. (2010). Protein secretion. In Methods in Molecular Biology. vol. 619, Chapter 7. Edited by A. Economou.New York, NY: Springer Science+Business Media, LLC. [Google Scholar]
  25. Narita S., Matsuyama S., Tokuda H. (2004). Lipoprotein trafficking in Escherichia coli . Arch Microbiol 182, 16 [View Article][PubMed] [Google Scholar]
  26. Park J. S., Lee W. C., Yeo K. J., Ryu K. -S., Kumarasiri M., Hesek D., Lee M., Mobashery S., Song J. H., other authors. (2012). Mechanism of anchoring of OmpA protein to the cell wall peptidoglycan of the gram-negative bacterial outer membrane. FASEB J 26, 219228 [View Article][PubMed] [Google Scholar]
  27. Parsons L. M., Lin F., Orban J. (2006). Peptidoglycan recognition by Pal, an outer membrane lipoprotein. Biochemistry 45, 21222128 [View Article][PubMed] [Google Scholar]
  28. Valentine C. H., Hellman J., Beasley-Topliffe L. K., Bagchi A., Warren H. S. (2006). Passive immunization to outer membrane proteins MLP and PAL does not protect mice from sepsis. Mol Med 12, 252258 [View Article][PubMed] [Google Scholar]
  29. Vollmer W., Bertsche U. (2008). Murein (peptidoglycan) structure, architecture and biosynthesis in Escherichia coli . Biochim Biophys Acta 1778, 17141734 [View Article][PubMed] [Google Scholar]
  30. Wang Y., Kim K. S. (2002). Role of OmpA and IbeB in Escherichia coli K1 invasion of brain microvascular endothelial cells in vitro and in vivo . Pediatr Res 51, 559563 [View Article][PubMed] [Google Scholar]
  31. Yeh Y. -C., Comolli L. R., Downing K. H., Shapiro L., McAdams H. H. (2010). The caulobacter Tol-Pal complex is essential for outer membrane integrity and the positioning of a polar localization factor. J Bacteriol 192, 48474858 [View Article][PubMed] [Google Scholar]
  32. Zakharian E., Reusch R. N. (2005). Kinetics of folding of Escherichia coli OmpA from narrow to large pore conformation in a planar bilayer. Biochemistry 44, 67016707 [View Article][PubMed] [Google Scholar]

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