Chapter 11 : Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818524/9781555816766_Chap11-1.gif /docserver/preview/fulltext/10.1128/9781555818524/9781555816766_Chap11-2.gif


Lipopolysaccharide (LPS) is the major component of the outer membrane of gram-negative bacteria and consists of three distinct structural domains: lipid A, a nonrepeating “core” oligosaccharide, and a distal repeated O-antigen polysaccharide. This chapter discusses the structure of the three regions, in order, as they extend out from the outer membrane, focusing on regulated alterations, modifications, and/or substitutions. The biosynthetic enzymes are either constitutively active or regulated by a variety of two-component regulatory systems, including PhoR/PhoB, PmrA/PmrB and/or PhoP/PhoQ. Deletion of IpxT in resulted in an increase in sensitivity to the cationic antimicrobial peptides (AMPs) polymyxin B, although experiments elucidating roles for lpxT in overall pathogenesis have yet to be undertaken. The chapter explores the regulation of one particular modification, that of phosphorylcholine (ChoP), on and lipooligosaccharide (LOS). Regulation of LPS core biosynthesis is not well understood, although some of the regulatory mechanisms for biosynthesis of Kdo and inner and outer core are emerging. The current evidence based on genetic and biophysical interaction studies of the Lpt proteins supports the transenvelope model. Further studies into the regulation of LPS should help provide a link between signals in the environment and the resulting outer membrane composition that are likely to have the most impact on host-pathogen interactions.

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Schematic representation of modifications of terminal residues of lipid A. The diagram shows the possible modifications outside of the terminal residues of lipid A. Chemical groups are color coded by the enzyme responsible for their action; a plus sign indicates an addition to the base structure, and a minus sign indicates a removal. Under each enzyme is the regulatory system that controls each its action; an upward-pointing arrow indicates a positive regulator, and a downward-pointing arrow indicates a negative regulator. doi:10.1128/9781555818524.ch11f1

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Pathway for the synthesis of Kdo. KdsD converts dribulose 5-phosphate to d-arabinose 5-phosphate. d-Arabinose 5-phosphate and phosphoenolpyruvate are combined by KdsA to form Kdo 8-phosphate. KdsC cleaves Kdo 8-phosphate to Kdo and inorganic phosphate. KdsB mediates the reaction of Kdo and CTP to form the activated sugar CMP-Kdo and PP. This active sugar is added to lipid IV in the inner membrane. doi:10.1128/9781555818524.ch11f2

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Structures of LPS core. Structures of known inner and outer cores for serovar Typhimurium (A), K-12 (B), and R1 (C), R2 (D), R3 (E), and R4 (F). All genes with known/proposed activities are indicated with gray arrows at the sites of activity. Adapted from A. Silipo and A. Molinaro, 2010. doi:10.1128/9781555818524.ch11f3

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Genetic organization of LPS core and LPS transport genes. (A) K-12 operon and known promoters. All promoters are indicated with interacting sigma factors. Genes for LPS transport are in white; the gene, part of the cation antiporter family, is shown in dark blue, and inner core genes are shown in black. (B) K-12 and operons with the gene and indicated promoters. Promoters are labeled with interacting sigma factors; promoters in black indicate active promoters, while blue promoters have not been proven active. Genes implicated in O-antigen synthesis are displayed in white, outer core genes are shown in blue, and inner core genes are shown in black. doi:10.1128/9781555818524.ch11f4

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Structure and visualization of LPS. (A) The typical gram-negative membrane is comprised of the inner membrane, the periplasm, and the outer membrane. The inner membrane is a phospholipid bilayer with integral and peripheral membrane proteins. (B) Representation of LPS structure showing the O antigen in blue, core in purple, and lipid A in yellow. Phosphates are shown as black circles. (C) LPS from Typhimurium strain 14028s and its isogenic Δ mutant. The lower-molecularweight bands demonstrate the banding pattern associated with increasing O-antigen side chains. The loss of long chain lengths due to the absence of is evident in the deletion mutant strain. Since is still contained in the genome of both strains, the very long chain length is still detected at the top of the gel. LPS was detected using Salmonella O Antiserum Factor 4 from Difco Laboratories. doi:10.1128/9781555818524.ch11f5

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

O-antigen loci from different gram-negative bacteria. Organizations of loci were obtained from the Genome home of NCBI (http://www.ncbi.nlm.nih.gov/sites/genome). Strains are as follows: PAO1; Typhimurium LT2, and 2a str 301. Locus tag numbers are provided underneath genes at the beginning and end of the operons. For reference, some of the other O-antigen-associated genes are as follows: , = PA4999 and = PA0938; Typhimurium, () = STM1332 and (second gene) = STM0589; and , = SF3666. doi:10.1128/9781555818524.ch11f6

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7
Figure 7

Wzy-dependent pathway for O-antigen synthesis and transfer across the inner membrane. The diagram shows that O antigens are synthesized on the Und-P and transferred via the Wzx, O-antigen flippase. The Wzy, O-antigen polymerase, extends the chains, the length of which is controlled by the Wzz O-antigen regulator. (Adapted from ) doi:10.1128/9781555818524.ch11f7

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 8
Figure 8

ABC transporter-dependent pathway for transfer across the inner membrane. The diagram shows the transfer of the Und- P-linked O antigen across the inner membrane by the ABC transporter, Wzm and Wzt. (Adapted from ) doi:10.1128/9781555818524.ch11f8

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 9
Figure 9

Diagram of the two proposed LptA transport mechanisms. In both models, MsbA transports the lipid A-core across the inner membrane. The completed Und-linked O antigen is transferred to the lipid A-core via the WaaL, O-antigen ligase (not shown). The left model shows that LptA docks with LptC and picks up the lipid A-core-O antigen and transports it across the periplasmic space, where it docks with the LptDE complex before being translocated across the outer membrane. In the right model, LptA oligomerizes to form a scaffold that allows the LPS to be transported across the periplasmic space. (Adapted from ) doi:10.1128/9781555818524.ch11f9

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Allison, G. E.,, and N. K. Verma. 2000. Serotype-converting bacteriophages and O-antigen modification in Shigella flexneri. Trends Microbiol. 81: 17 23.
2. Alpuche Aranda, C. M.,, J. A. Swanson,, W. P. Loomis,, and S. I. Miller. 1992. Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. Proc. Natl. Acad. Sci. USA 89: 10079 10083.
3. Asensio, C. J.,, M. E. Gaillard,, G. Moreno,, D. Bottero,, E. Zurita,, M. Rumbo,, P. van derLey,, A. van der Ark,, and D. Hozbor. 2011. Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate. Vaccine 29: 1649 1656.
4. Bader, M. W.,, S. Sanowar,, M. E. Daley,, A. R. Schneider,, U. Cho,, W. Xu,, R. E. Klevit,, H. Le Moual,, and S. I. Miller. 2005. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122: 461 472.
5. Bailey, M. J.,, C. Hughes,, and V. Koronakis. 2000. In vitro recruitment of the RfaH regulatory protein into a specialised transcription complex, directed by the nucleic acid ops element. Mol. Gen. Genet. 262: 1052 1059.
6. Bastin, D. A.,, G. Stevenson,, P. K. Brown,, A. Haase,, and P. R. Reeves. 1993. Repeat unit polysaccharides of bacteria: a model for polymerization resembling that of ribosomes and fatty acid synthetase, with a novel mechanism for determining chain length. Mol. Microbiol. 7: 725 734.
7. Belden, W. J.,, and S. I. Miller. 1994. Further characterization of the PhoP regulon: identification of new PhoP-activated virulence loci. Infect. Immun. 62: 5095 5101.
8. Belunis, C. J.,, T. Clementz,, S. M. Carty,, and C. R. Raetz. 1995. Inhibition of lipopolysaccharide biosynthesis and cell growth following inactivation of the kdtA gene in Escherichia coli. J. Biol. Chem. 270: 27646 27652.
9. Bengoechea, J. A.,, L. Zhang,, P. Toivanen,, and M. Skurnik. 2002. Regulatory network of lipopolysaccharide O-antigen biosynthesis in Yersinia enterocolitica includes cell envelope-dependent signals. Mol. Microbiol. 44: 1045 1062.
10. Beutler, B. 2005. The Toll-like receptors: analysis by forward genetic methods. Immunogenetics 57: 385 392.
11. Bishop, R. E. 2008. Structural biologyof membrane-intrinsic beta-barrel enzymes: sentinels of the bacterial outermembrane. Biochim. Biophys. Acta 1778: 1881 1896.
12. Bishop, R. E.,, H. S. Gibbons,, T. Guina,, M. S. Trent,, S. I. Miller,, and C. R. Raetz. 2000. Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria. EMBO J. 19: 5071 5080.
13. Biswas, T.,, L. Yi,, P. Aggarwal,, J. Wu,, J. R. Rubin,, J. A. Stuckey,, R. W. Woodard,, and O. V. Tsodikov. 2009. The tail of KdsC: conformational changes control the activity of a haloacid dehalogenase superfamily phosphatase. J. Biol. Chem. 284: 30594 30603.
14. Bittner, M.,, S. Saldias,, F. Altamirano,, M. A. Valvano,, and I. Contreras. 2004. RpoS and RpoN are involved in the growth-dependent regulation of rfaH transcription and O antigen expression in Salmonella enterica serovar Typhi. Microb. Pathog. 36: 19 24.
15. Bittner, M.,, S. Saldias,, C. Estevez,, M. Zaldivar,, C. L. Marolda,, M. A. Valvano,, and I. Contreras. 2002. O-antigen expressionin Salmonella enterica serovar Typhi is regulated by nitrogen availability through RpoN-mediated transcriptional control of the rfaH gene. Microbiology 148( Pt. 12): 3789 3799.
16. Bos, M. P.,, and J. Tommassen. 2011. The LptD chaperone LptE is not directly involved in lipopolysaccharide transport in Neisseria meningitidis. J. Biol. Chem. 286: 28688 28696.
17. Bowyer, A.,, J. Baardsnes,, E. Ajamian,, L. Zhang,, and M. Cygler. 2011. Characterization of interactions between LPS transport proteins of the Lpt system. Biochem. Biophys. Res. Commun. 404: 1093 1098.
18. Broadbent, S. E.,, M. R. Davies,, and M. W. van der Woude. 2010. Phase variationcontrols expression of Salmonella lipopolysaccharide modification genes by a DNAmethylation-dependent mechanism. Mol. Microbiol. 77: 337 353.
19. Bronner, D.,, B. R. Clarke,, and C. Whitfield. 1994. Identification of an ATP-binding cassette transport system required for translocation of lipopolysaccharide O-antigen side-chains across the cytoplasmic membrane of Klebsiella pneumoniae serotype O1. Mol. Microbiol. 14: 505 519.
20. Brozek, K. A.,, and C. R. Raetz. 1990. Biosynthesis of lipid A in Escherichia coli. Acyl carrier protein-dependent incorporation of laurate and myristate. J. Biol. Chem. 265: 15410 15417.
21. Burns, S. M.,, and S. I. Hull. 1998. Comparison of loss of serum resistance by defined lipopolysaccharide mutants and an acapsular mutant of uropathogenic Escherichia coli O75:K5. Infect. Immun. 66: 4244 4253.
22. Carter, J. A.,, C. J. Blondel,, M. Zaldivar,, S. A. Alvarez,, C. L. Marolda,, M. A. Valvano,, and I. Contreras. 2007. O-antigen modal chainlength in Shigella flexneri 2a is growth-regulated through RfaH-mediatedtranscriptional control of the wzy gene. Microbiology 153( Pt. 10): 3499 3507.
23. Carter, J. A.,, J. C. Jimenez,, M. Zaldivar,, S. A. Alvarez,, C. L. Marolda,, M. A. Valvano,, and I. Contreras. 2009. The cellular level ofO-antigen polymerase Wzy determines chain length regulation by WzzB and WzzpHS-2 in Shigellaflexneri 2a. Microbiology 155( Pt.10): 3260 3269.
24. Chalabaev, S.,, T. H. Kim,, R. Ross,, A. Derian,, and D. L. Kasper. 2010. 3-Deoxy-D-manno-octulosonic acid (Kdo) hydrolase identified in Francisella tularensis, Helicobacter pylori, and Legionella pneumophila. J. Biol. Chem. 285: 34330 34336.
25. Chimalakonda, G.,, N. Ruiz,, S. S. Chng,, R. A. Garner,, D. Kahne,, and T. J. Silhavy. 2011. Lipoprotein LptE is required for the assembly of LptD by the beta-barrel assembly machine in the outer membrane of Escherichia coli. Proc. Natl. Acad. Sci. USA 108: 2492 2497.
26. Chng, S. S.,, L. S. Gronenberg,, and D. Kahne. 2010a. Proteins required for lipopolysaccharide assembly in Escherichia coli form a transenvelope complex. Biochemistry 49: 4565 4567.
27. Chng, S. S.,, N. Ruiz,, G. Chimalakonda,, T. J. Silhavy,, and D. Kahne. 2010b. Characterization of the two-protein complex in Escherichia coli responsible for lipopolysaccharide assembly at the outer membrane. Proc. Natl. Acad. Sci. USA 107: 5363 5368.
28. Cipolla, L.,, A. Polissi,, C. Airoldi,, P. Galliani,, P. Sperandeo,, and F. Nicotra. 2009. The Kdo biosynthetic pathway toward OM biogenesis as target in antibacterial drug design and development. Curr. Drug Discov. Technol. 6: 19 33.
29. Clementz, T. 1992. The gene coding for 3-deoxy-manno-octulosonic acid transferase and the rfaQ gene are transcribed from divergently arranged promoters in Escherichia coli. J. Bacteriol. 174: 7750 7756.
30. Clementz, T.,, J. J. Bednarski,, and C. R. Raetz. 1996. Function of the htrB high temperature requirement gene of Escherchia coli in theacylation of lipid A: HtrB catalyzed incorporation of laurate. J. Biol.Chem. 271: 12095 12102.
31. Coats, S. R.,, C. T. Do,, L. M. Karimi-Naser,, P. H. Braham,, and R. P. Darveau. 2007. Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Cell. Microbiol. 9: 1191 1202.
32. Comstock, L. E.,, and D. L. Kasper. 2006. Bacterial glycans: key mediators of diverse host immune responses. Cell 126: 847 850.
33. Corsaro, M. M.,, E. Parrilli,, R. Lanzetta,, T. Naldi,, G. Pieretti,, B. Lindner,, A. Carpentieri,, M. Parrilli,, and M. L. Tutino. 2009. The presence of OMP inclusion bodies in a Escherichia coli K-12 mutated strain is not related to lipopolysaccharide structure. J. Biochem. 146: 231 240.
34. Cox, A. D.,, J. C. Wright,, J. Li,, D. W. Hood,, E. R. Moxon,, and J. C. Richards. 2003. Phosphorylation of the lipid A region of meningococcal lipopolysaccharide: identification of a family of transferases that add phosphoethanolamine to lipopolysaccharide. J. Bacteriol. 185: 3270 3277.
35. Creeger, E. S.,, and L. I. Rothfield. 1979. Cloning of genes for bacterial glycosyltransferases. I. Selection of hybrid plasmids carrying genes for two glucosyltransferases. J. Biol. Chem. 254: 804 810.
36. Cullen, T. W.,, and M. S. Trent. 2010. A link between the assembly of flagella and lipooligosaccharide of the Gram-negative bacterium Campylobacter jejuni. Proc. Natl. Acad. Sci. USA 107: 5160 5165.
37. Daniels, C.,, C. Griffiths,, B. Cowles,, and J. S. Lam. 2002. Pseudomonas aeruginosa O-antigen chain length is determined before ligation to lipid A core. Environ. Microbiol. 4: 883 897.
38. Daniels, C.,, and R. Morona. 1999. Analysis of Shigella flexneri wzz (Rol) function by mutagenesis and cross-linking: wzz is able to oligomerize. Mol. Microbiol. 34: 181 194.
39. Dartigalongue, C.,, D. Missiakas,, and S. Raina. 2001. Characterization of the Escherichia coli sigma E regulon. J. Biol. Chem. 276:20866-20875.
40. Darveau, R. P.,, T. T. Pham,, K. Lemley,, R. A. Reife,, B. W. Bainbridge,, S. R. Coats,, W. N. Howald,, S. S. Way,, and A. M. Hajjar. 2004. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both Toll-like receptors 2 and 4. Infect. Immun. 72: 5041 5051.
41. de Cock, H.,, K. Brandenburg,, A. Wiese,, O. Holst,, and U. Seydel. 1999. Non-lamellar structure and negative charges of lipopolysaccharides required for efficient folding of outer membrane protein PhoE of Escherichia coli. J. Biol. Chem. 274: 5114 5119.
42. de Cock, H.,, and J. Tommassen. 1996. Lipopolysaccharides and divalent cations are involved in the formation of an assembly-competent intermediate of outer-membrane protein PhoE of E. coli. EMBO J. 15: 5567 5573.
43. Delgado, M. A.,, C. Mouslim,, and E. A. Groisman. 2006. The PmrA/PmrB and RcsC/YojN/RcsB systems control expression of the Salmonella O-antigen chain length determinant. Mol. Microbiol. 60: 39 50.
44. Derzelle, S.,, E. Turlin,, E. Duchaud,, S. Pages,, F. Kunst,, A. Givaudan,, and A. Danchin. 2004. The PhoP-PhoQ two-component regulatory system of Photorhabdus luminescens is essential for virulence in insects. J. Bacteriol. 186: 1270 1279.
45. Doerrler, W. T.,, H. S. Gibbons,, and C. R. Raetz. 2004. MsbA-dependent translocation of lipids across the inner membrane of Escherichia coli. J. Biol. Chem. 279: 45102 45109.
46. El Ghachi, M.,, A. Derbise,, A. Bouhss,, and D. Mengin-Lecreulx. 2005. Identificationof multiple genes encoding membrane proteins with undecaprenyl pyrophosphate phosphatase (UppP)activity in Escherichia coli. J. Biol. Chem. 280: 18689 18695.
47. Ernst, R. K.,, E. C. Yi,, L. Guo,, K. B. Lim,, J. L. Burns,, M. Hackett,, and S. I. Miller. 1999. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 286: 1561 1565.
48. Fox, K. L.,, J. Li,, E. K. Schweda,, V. Vitiazeva,, K. Makepeace,, M. P. Jennings,, E. R. Moxon,, and D. W. Hood. 2008. Duplicate copies of lic1 direct the addition of multiple phosphocholine residues in the lipopolysaccharide of Haemophilus influenzae. Infect. Immun. 76: 588 600.
49. Franco, A. V.,, D. Liu,, and P. R. Reeves. 1998. The Wzz (Cld) protein in Escherichia coli: amino acid sequence variation determines O-antigen chain length specificity. J. Bacteriol. 180: 2670 2675.
50. Frirdich, E.,, B. Lindner,, O. Holst,, and C. Whitfield. 2003. Overexpression of the waaZ gene leads to modification of the structure of the inner core region of Escherichia coli lipopolysaccharide, truncation of the outer core, and reduction of the amount of O polysaccharide on the cell surface. J. Bacteriol. 185: 1659 1671.
51. Frirdich, E.,, and C. Whitfield. 2005. Lipopolysaccharide inner core oligosaccharide structure and outer membrane stability in human pathogens belonging to the Enterobacteriaceae. J. Endotoxin Res. 11: 133 144.
52. Garcia Vescovi, E.,, F. C. Soncini,, and E. A. Groisman. 1996. Mg 2+ as an extracellular signal: environmental regulation of Salmonella virulence. Cell 84: 165 174.
53. Gibbons, H. S.,, S. R. Kalb,, R. J. Cotter,, and C. R. Raetz. 2005. Role of Mg 2+ and pH in the modification of Salmonella lipid A after endocytosis by macrophage tumour cells. Mol. Microbiol. 55: 425 440.
54. Gibbons, H. S.,, S. Lin,, R. J. Cotter,, and C. R. Raetz. 2000. Oxygen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in Salmonella typhimurium lipid A. Function of LpxO, a new Fe 2+/alpha-ketoglutarate-dependent dioxygenase homologue. J. Biol. Chem. 275: 32940 32949.
55. Golden, N. J.,, and D. W. Acheson. 2002. Identification of motility and autoagglutination Campylobacter jejuni mutants by random transposon mutagenesis. Infect. Immun. 70: 1761 1771.
56. Grizot, S.,, M. Salem,, V. Vongsouthi,, L. Durand,, F. Moreau,, H. Dohi,, S. Vincent,, S. Escaich,, and A. Ducruix. 2006. Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with ADP and ADP-2-deoxy-2-fluoro heptose. J. Mol. Biol. 363: 383 394
57. Groisman, E. A.,, E. Chiao,, C. J. Lipps,, and F. Heffron. 1989. Salmonella typhimurium phoP virulence gene is a transcriptional regulator. Proc. Natl. Acad. Sci. USA 86: 7077 7081.
58. Gronow, S.,, W. Brabetz,, and H. Brade. 2000. Comparative functional characterization in vitro of heptosyltransferase I (WaaC) and II (WaaF) from Escherichia coli. Eur. J. Biochem. 267: 6602 6611.
59. Gunn, J. S.,, K. B. Lim,, J. Krueger,, K. Kim,, L. Guo,, M. Hackett,, and S. I. Miller. 1998. PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance. Mol. Microbiol. 27: 1171 1182.
60. Gunn, J. S.,, and S. I. Miller. 1996. PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J. Bacteriol. 178: 6857 6864.
61. Gunn, J. S.,, S. S. Ryan,, J. C. Van Velkinburgh,, R. K. Ernst,, and S. I. Miller. 2000. Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar Typhimurium. Infect. Immun. 68: 6139 6146.
62. Guo, H.,, K. Lokko,, Y. Zhang,, W. Yi,, Z. Wu,, and P. G. Wang. 2006. Overexpression and characterization of Wzz of Escherichia coli O86:H2. Protein Expr. Purif. 48: 49 55.
63. Guo, L.,, K. B. Lim,, C. M. Poduje,, M. Daniel,, J. S. Gunn,, M. Hackett,, and S. I. Miller. 1998. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 95: 189 198.
64. Hajjar, A. M.,, R. K. Ernst,, J. H. Tsai,, C. B. Wilson,, and S. I. Miller. 2002. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat. Immunol. 3: 354 359.
65. Hankins, J. V.,, J. A. Madsen,, D. K. Giles,, B. M. Childers,, K. E. Klose,, J. S. Brodbelt,, and M. S. Trent. 2011. Elucidation of a novel Vibrio cholerae lipid A secondary hydroxy-acyltransferase and its role in innate immune recognition. Mol. Microbiol. 81: 1313 1329.
66. Hankins, J. V.,, and M. S. Trent. 2009. Secondary acylation of Vibrio cholerae lipopolysaccharide requires phosphorylation of Kdo. J. Biol. Chem. 284: 25804 25812.
67. Hegge, F. T.,, P. G. Hitchen,, F. E. Aas,, H. Kristiansen,, C. Lovold,, W. Egge-Jacobsen,, M. Panico,, W. Y. Leong,, V. Bull,, M. Virji,, H. R. Morris,, A. Dell,, and M. Koomey. 2004. Unique modifications with phosphocholine and phosphoethanolamine define alternate antigenic forms of Neisseria gonorrhoeae type IV pili. Proc. Natl. Acad. Sci. USA 101: 10798 10803.
68. Heinrichs, D. E.,, M. A. Monteiro,, M. B. Perry,, and C. Whitfield. 1998a. The assembly system for the lipopolysaccharide R2 core-type of Escherichia coli is a hybrid of those found in Escherichia coli K-12 and Salmonella enterica. Structure and function of the R2 WaaK and WaaL homologs. J. Biol. Chem. 273: 8849 8859.
69. Heinrichs, D. E.,, J. A. Yethon,, P. A. Amor,, and C. Whitfield. 1998b. The assembly system for the outer core portion of R1- and R4-type lipopolysaccharides of Escherichia coli. The R1 core-specific beta-glucosyltransferase provides a novel attachment site for O-polysaccharides. J. Biol. Chem. 273: 29497 29505.
70. Heinrichs, D. E.,, J. A. Yethon,, and C. Whitfield. 1998c. Molecular basis for structural diversity in the core regions of the lipopolysaccharides of Escherichia coli and Salmonella enterica. Mol. Microbiol. 30: 221 232.
71. Helander, I. M.,, I. Kilpelainen,, and M. Vaara. 1994. Increased substitution of phosphate groups in lipopolysaccharides and lipid A of the polymyxin-resistant pmrA mutants of Salmonella typhimurium: a 31P-NMR study. Mol. Microbiol. 11: 481 487.
72. Herrera, C. M.,, J. V. Hankins,, and M. S. Trent. 2010. Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides. Mol. Microbiol. 76: 1444 1460.
73. Hitchen, P. G.,, J. L. Prior,, P. C. Oyston,, M. Panico,, B. W. Wren,, R.W. Titball,, H. R. Morris,, and A. Dell. 2002. Structural characterization of lipo-oligosaccharide (LOS) from Yersinia pestis: regulation of LOS structure by the PhoPQ system. Mol. Microbiol. 44: 1637 1650.
74. Hobbs, M.,, and P. R. Reeves. 1994. The JUMPstart sequence: a 39 bp element common to several polysaccharide gene clusters. Mol. Microbiol. 12: 855 856.
75. Hong, W.,, B. Pang,, S. West-Barnette,, and W. E. Swords. 2007. Phosphorylcholine expression by nontypeable Haemophilus influenzae correlates with maturation of biofilm communities in vitro and in vivo. J. Bacteriol. 189: 8300 8307.
76. Hwang, P. M.,, W. Y. Choy,, E. I. Lo,, L. Chen,, J. D. Forman-Kay,, C.R. Raetz,, G. G. Prive,, R. E. Bishop,, and L. E. Kay. 2002. Solution structure and dynamics of the outer membrane enzyme PagP by NMR. Proc. Natl. Acad. Sci. USA 99: 13560 13565.
77. Ingram, B. O.,, C. Sohlenkamp,, O. Geiger,, and C. R. Raetz. 2010. Altered lipid A structuresand polymyxin hypersensitivity of Rhizobium etli mutants lacking the LpxE and LpxFphosphatases. Biochim. Biophys. Acta 1801: 593 604.
78. Isobe, T.,, K. A. White,, A. G. Allen,, M. Peacock,, C. R. Raetz,, and D. J. Maskell. 1999. Bordetella pertussis waaA encodes a monofunctional 2-keto-3-deoxy-D-manno-octulosonic acid transferase that can complement an Escherichia coli waaA mutation. J. Bacteriol. 181: 2648 2651.
79. Ivanov, I. E.,, E. N. Kintz,, L. A. Porter,, J. B. Goldberg,, N. A. Burnham,, and T. A. Camesano. 2011. Relating the physical properties of Pseudomonas aeruginosa lipopolysaccharides to virulence by atomic force microscopy. J. Bacteriol. 193: 1259 1266.
80. Jimenez, N.,, R. Canals,, M. T. Salo,, S. Vilches,, S. Merino,, and J.M. Tomas. 2008. The Aeromonas hydrophila wb*O34 gene cluster: genetics and temperature regulation. J. Bacteriol. 190: 4198 4209.
81. Joiner, K. A.,, C. H. Hammer,, E. J. Brown,, R. J. Cole,, and M.M. Frank. 1982. Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from Salmonella minnesota S218 without causing bacterial death. J. Exp. Med. 155: 797 808.
82. Kadam, S. K.,, A. Rehemtulla,, and K. E. Sanderson. 1985. Cloning of rfaG, B, I, and J genes for glycosyltransferase enzymes for synthesis of the lipopolysaccharide core of Salmonella typhimurium. J. Bacteriol. 161: 277 284.
83. Kaluzny, K.,, P. D. Abeyrathne,, and J. S. Lam. 2007. Coexistence of two distinct versions of O-antigen polymerase, Wzy-alpha and Wzy-beta, in Pseudomonas aeruginosa serogroup O2 and their contributions to cell surface diversity. J. Bacteriol. 189: 4141 4152.
84. Kalynych, S.,, X. Ruan,, M. A. Valvano,, and M. Cygler. 2011. Structure-guided investigation of lipopolysaccharide O-antigen chain length regulators reveals regions critical for modal length control. J. Bacteriol. 193: 3710 3721.
85. Kaniuk, N. A.,, E. Vinogradov,, J. Li,, M. A. Monteiro,, and C. Whitfield. 2004. Chromosomal and plasmid-encoded enzymes are required for assembly of the R3-type core oligosaccharide in the lipopolysaccharide of Escherichia coli O157:H7. J. Biol. Chem. 279: 31237 31250.
86. Karbarz, M. J.,, S. R. Kalb,, R. J. Cotter,, and C. R. Raetz. 2003. Expression cloning and biochemical characterization of a Rhizobium leguminosarum lipid A 1-phosphatase. J. Biol. Chem. 278: 39269 39279.
87. Karow, M.,, O. Fayet,, A. Cegielska,, T. Ziegelhoffer,, and C. Georgopoulos. 1991a. Isolation and characterization of the Escherichia coli htrB gene, whose product is essential for bacterial viability above 33°C in rich media. J. Bacteriol. 173: 741 750.
88. Karow, M.,, S. Raina,, C. Georgopoulos,, and O. Fayet. 1991b. Complex phenotypes of null mutations in the htr genes, whose products are essential for Escherichia coli growth at elevated temperatures. Res. Microbiol. 142: 289 294.
89. Karow, M.,, and C. Georgopoulos. 1991. Sequencing, mutational analysis, and transcriptional regulation of the Escherichia coli htrB gene. Mol. Microbiol. 5: 2285 2292.
90. Kato, A.,, and E. A. Groisman. 2004. Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor. Genes Dev. 18: 2302 2313.
91. Kawano, M.,, T. Manabe,, and K. Kawasaki. 2010. Salmonella enterica serovar Typhimurium lipopolysaccharide deacylation enhances its intracellular growth within macrophages. FEBS Lett. 584: 207 212.
92. Kawasaki, K.,, K. China,, and M. Nishijima. 2007. Release of the lipopolysaccharide deacylase PagL from latency compensates for a lack of lipopolysaccharide aminoarabinose modification-dependent resistance to the antimicrobial peptide polymyxin B in Salmonella enterica. J. Bacteriol. 189: 4911 4919.
93. Kawasaki, K.,, R. K. Ernst,, and S. I. Miller. 2004a. 3-O-deacylation of lipidA by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulatessignaling through Toll-like receptor 4. J. Biol. Chem. 279: 20044 20048.
94. Kawasaki, K.,, R. K. Ernst,, and S. I. Miller. 2004b. Deacylation and palmitoylation of lipid A by Salmonellae outer membrane enzymes modulate host signaling through Toll-like receptor 4. J. Endotoxin Res. 10: 439 444.
95. Kawasaki, K.,, R. K. Ernst,, and S. I. Miller. 2005. Inhibition of Salmonella enterica serovar Typhimurium lipopolysaccharide deacylation by aminoarabinose membrane modification. J. Bacteriol. 187: 2448 2457.
96. Keenleyside, W. J.,, and C. Whitfield. 1996. A novel pathway for O-polysaccharide biosynthesis in Salmonella enterica serovar Borreze. J. Biol. Chem. 271: 28581 28592.
97. Keenleyside, W. J.,, and C. Whitfield,. 1999. Genetics andbiosynthesis of lipopolysaccharide O-antigens, p. 331 358. In C. M. H. Brade,, S. M. Opal,, and S. N. Vogel (ed.), Endotoxin in Health and Disease. Marcel Dekker, Inc., New York, NY.
98. Kim, S. H.,, K. S. Kim,, S. R. Lee,, E. Kim,, M. S. Kim,, E. Y. Lee,, Y. S. Gho,, J. W. Kim,, R. E. Bishop,, and K. T. Chang. 2009. Structural modifications of outer membrane vesicles to refine them as vaccine delivery vehicles. Biochim. Biophys. Acta 1788: 2150 2159.
99. Kintz, E.,, and J. B. Goldberg. 2008. Regulation of lipopolysaccharide O antigen expression in Pseudomonas aeruginosa. Future Microbiol. 3: 191 203.
100. Kintz, E.,, J. M. Scarff,, A. DiGiandomenico,, and J. B. Goldberg. 2008. Lipopolysaccharide O-antigen chain length regulation in Pseudomonas aeruginosa serogroup O11 strain PA103. J. Bacteriol. 190: 2709 2716.
101. Knirel, Y. A.,, B. Lindner,, E. Vinogradov,, R. Z. Shaikhutdinova,, S. N. Senchenkova,, N. A. Kocharova,, O. Holst,, G. B. Pier,, and A. P. Anisimov. 2005. Cold temperature-induced modifications to the composition and structure of the lipopolysaccharide of Yersinia pestis. Carbohydr. Res. 340: 1625 1630.
102. Koprivnjak, T.,, and A. Peschel. 2011. Bacterial resistance mechanisms against host defense peptides. Cell. Mol. Life Sci. 68: 2243 2254.
103. Koretke, K. K.,, A. N. Lupas,, P. V. Warren,, M. Rosenberg,, and J. R. Brown. 2000. Evolution of two-componentsignal transduction. Mol. Biol. Evol. 17: 1956 1970.
104. Kox, L. F.,, M. M. Wosten,, and E. A. Groisman. 2000. A small protein thatmediates the activation of a two-component system by another two-component system. EMBO J. 19: 1861 1872.
105. Kulshin, V. A.,, U. Zahringer,, B. Lindner,, C. E. Frasch,, C. M. Tsai,, B.A. Dmitriev,, and E. T. Rietschel. 1992. Structural characterization of the lipid A component of pathogenic Neisseria meningitidis. J. Bacteriol. 174: 1793 1800.
106. Kuzio, J.,, and A. M. Kropinski. 1983. O-antigen conversion in Pseudomonas aeruginosa PAO1 by bacteriophage D3. J. Bacteriol. 155: 203 212.
107. Lamarche, M. G.,, S. H. Kim,, S. Crepin,, M. Mourez,, N. Bertrand,, R. E. Bishop,, J. D. Dubreuil,, and J. Harel. 2008a. Modulation of hexa-acyl pyrophosphate lipid A population under Escherichia coli phosphate (Pho) regulon activation. J. Bacteriol. 190: 5256 5264.
108. Lamarche, M. G.,, B. L. Wanner,, S. Crepin,, and J. Harel. 2008b. The phosphate regulon and bacterial virulence: a regulatory network connecting phosphate homeostasis and pathogenesis. FEMS Microbiol. Rev. 32: 461 473.
109. Larue, K.,, M. S. Kimber,, R. Ford,, and C. Whitfield. 2009. Biochemical and structural analysis of bacterial O-antigen chain length regulator proteins reveals a conserved quaternary structure. J. Biol. Chem. 284: 7395 7403.
110. Lee, H.,, F. F. Hsu,, J. Turk,, and E. A. Groisman. 2004. The PmrA-regulated pmrC gene mediates phosphoethanolamine modification of lipid A and polymyxin resistance in Salmonella enterica. J. Bacteriol. 186: 4124 4133.
111. Lee, J. H.,, K. L. Lee,, W. S. Yeo,, S. J. Park,, and J. H. Roe. 2009a. SoxRS-mediated lipopolysaccharide modification enhances resistance against multiple drugs in Escherichia coli. J. Bacteriol. 191: 4441 4450.
112. Lee, S. R.,, S. H. Kim,, K. J. Jeong,, K. S. Kim,, Y. H. Kim,, S. J. Kim,, E. Kim,, J. W. Kim,, and K. T. Chang. 2009b. Multi-immunogenic outer membrane vesicles derived from an MsbB-deficient S almonella enterica serovar Typhimurium mutant. J. Microbiol. Biotechnol. 19: 1271 1279.
113. Lewis, L. A.,, B. Choudhury,, J. T. Balthazar,, L. E. Martin,, S. Ram,, P. A. Rice,, D. S. Stephens,, R. Carlson,, and W. M. Shafer. 2009. Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum. Infect. Immun. 77: 1112 1120.
114. Lippa, A. M.,, and M. Goulian. 2009. Feedback inhibition in the PhoQ/PhoP signaling system by a membrane peptide. PLoS Genet. 5: e1000788.
115. Llama-Palacios, A.,, E. Lopez-Solanilla,, and P. Rodriguez-Palenzuela. 2005. Role of the PhoP-PhoQ system in the virulence of Erwinia chrysanthemi strain 3937: involvement in sensitivity to plant antimicrobial peptides, survival at acid pH, and regulation of pectolytic enzymes. J. Bacteriol. 187: 2157 2162.
116. Loomis, W. F.,, A. Kuspa,, and G. Shaulsky. 1998. Two-component signal transduction systems in eukaryotic microorganisms. Curr. Opin. Microbiol. 1: 643 648.
117. Lysenko, E. S.,, J. Gould,, R. Bals,, J. M. Wilson,, and J. N. Weiser. 2000. Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect. Immun. 68: 1664 1671.
118. Macarthur, I.,, J. W. Jones,, D. R. Goodlett,, R. K. Ernst,, and A. Preston. 2011. The role of pagL and lpxO in Bordetella bronchiseptica lipid A biosynthesis. J. Bacteriol. 193: 4726 4735.
119. Macfarlane, E. L.,, A. Kwasnicka,, and R. E. Hancock. 2000. Role of Pseudomonas aeruginosa PhoP-PhoQ in resistance to antimicrobial cationic peptidesand aminoglycosides. Microbiology 146( Pt.10): 2543 2554.
120. Macfarlane, E. L.,, A. Kwasnicka,, M. M. Ochs,, and R. E. Hancock. 1999. PhoP-PhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol. Microbiol. 34: 305 316.
121. Mackinnon, F. G.,, A. D. Cox,, J. S. Plested,, C. M. Tang,, K. Makepeace,, P. A. Coull,, J. C. Wright,, R. Chalmers,, D. W. Hood,, J. C. Richards,, and E. R. Moxon. 2002. Identification of a gene ( lpt-3) required for the addition of phosphoethanolamine to the lipopolysaccharide inner core of Neisseria meningitidis and its role in mediating susceptibility to bactericidal killing and opsonophagocytosis. Mol. Microbiol. 43: 931 943.
122. Marchal, K.,, S. De Keersmaecker,, P. Monsieurs,, N. van Boxel,, K. Lemmens,, G. Thijs,, J. Vanderleyden,, and B. De Moor. 2004. In silico identification and experimental validation of PmrAB targets in Salmonella typhimurium by regulatory motif detection. Genome Biol. 5: R9.
123. Marolda, C. L.,, and M. A. Valvano. 1998. Promoter region of the Escherichia coli O7-specific lipopolysaccharide gene cluster: structural and functional characterization of an upstream untranslated mRNA sequence. J. Bacteriol. 180: 3070 3079.
124. Martorana, A. M.,, P. Sperandeo,, A. Polissi,, and G. Deho. 2011. Complex transcriptional organization regulates an Escherichia coli locus implicated in lipopolysaccharide biogenesis. Res. Microbiol. 162: 470 482.
125. McGee, D. J.,, A. E. George,, E. A. Trainor,, K. E. Horton,, E. Hildebrandt,, and T. L. Testerman. 2011. Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37. Antimicrob. Agents Chemother. 55: 2897 2904.
126. Miller, S. I.,, A. M. Kukral,, and J. J. Mekalanos. 1989. A two-component regulatory system ( phoP phoQ) controls Salmonella typhimurium virulence. Proc. Natl. Acad. Sci. USA 86: 5054 5058.
127. Mohan, S.,, and C. R. Raetz. 1994. Endotoxin biosynthesis in Pseudomonas aeruginosa: enzymatic incorporation of laurate before 3-deoxy-D-manno-octulosonate. J. Bacteriol. 176: 6944 6951.
128. Moran, A. P.,, B. Lindner,, and E. J. Walsh. 1997. Structural characterization of the lipid A component of Helicobacter pylori rough- and smooth-form lipopolysaccharides. J. Bacteriol. 179: 6453 6463.
129. Morona, R.,, L. Purins,, A. Tocilj,, A. Matte,, and M. Cygler. 2009. Sequence-structure relationships in polysaccharide co-polymerase (PCP) proteins. Trends Biochem. Sci. 34: 78 84.
130. Morona, R.,, L. vanden Bosch,, and P. A. Manning. 1995. Molecular, genetic, andtopological characterization of O-antigen chain length regulation in Shigellaflexneri. J. Bacteriol. 177: 1059 1068.
131. Moss, J. E.,, P. E. Fisher,, B. Vick,, E. A. Groisman,, and A. Zychlinsky. 2000. The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri. Cell. Microbiol. 2: 443 452.
132. Mosser, J. L.,, and A. Tomasz. 1970. Choline-containing teichoic acid as a structural component of pneumococcal cell wall and its role in sensitivity to lysis by an autolytic enzyme. J. Biol. Chem. 245: 287 298.
133. Munford, R. S. 2008. Sensing gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect. Immun. 76: 454 465.
134. Murata, T.,, W. Tseng,, T. Guina,, S. I. Miller,, and H. Nikaido. 2007. PhoPQ-mediated regulation produces a more robust permeability barrier in the outer membrane of Salmonella enterica serovar Typhimurium. J. Bacteriol. 189: 7213 7222.
135. Murray, G. L.,, S. R. Attridge,, and R. Morona. 2003. Regulation of Salmonella typhimurium lipopolysaccharide O antigen chain length is required for virulence; identification of FepE as a second Wzz. Mol. Microbiol. 47: 1395 1406.
136. Murray, G. L.,, S. R. Attridge,, and R. Morona. 2005. Inducible serum resistance in Salmonella typhimurium is dependent on wzz ( fepE)-regulated very long O antigen chains. Microbes Infect. 7: 1296 1304.
137. Murray, G. L.,, S. R. Attridge,, and R. Morona. 2006. Altering the length of the lipopolysaccharide O antigen has an impact on the interaction of Salmonella enterica serovar Typhimurium with macrophages and complement. J. Bacteriol. 188: 2735 2739.
138. Nagy, G.,, T. Palkovics,, A. Otto,, H. Kusch,, B. Kocsis,, U. Dobrindt,, S. Engelmann,, M. Hecker,, L. Emody,, T. Pal,, and J. Hacker. 2008. “Gently rough”: the vaccine potential of a Salmonella enterica regulatory lipopolysaccharide mutant. J. Infect. Dis. 198: 1699 1706.
139. Newton, G. J.,, C. Daniels,, L. L. Burrows,, A. M. Kropinski,, A. J. Clarke,, and J. S. Lam. 2001. Three-component-mediated serotype conversion in Pseudomonas aeruginosa by bacteriophage D3. Mol. Microbiol. 39: 1237 1247.
140. Nikaido, H. 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 67: 593 656.
141. Oertelt, C.,, B. Lindner,, M. Skurnik,, and O. Holst. 2001. Isolation and structural characterization of an R-form lipopolysaccharide from Yersinia enterocolitica serotype O:8. Eur. J. Biochem. 268: 554 564.
142. O’Neill, L. A. 2008a. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol. Rev. 226: 10 18.
143. O’Neill, L. A. 2008b. When signaling pathways collide: positive and negative regulation of Toll-like receptor signal transduction. Immunity 29: 12 20.
144. Oyston, P. C.,, N. Dorrell,, K. Williams,, S. R. Li,, M. Green,, R. W. Titball,, and B. W. Wren. 2000. The response regulator PhoP is important for survival under conditions of macrophage-induced stress and virulence in Yersinia pestis. Infect. Immun. 68: 3419 3425.
145. Papadopoulos, M.,, and R. Morona. 2010. Mutagenesis and chemical cross-linking suggest that Wzz dimer stability and oligomerization affect lipopolysaccharide O-antigen modal chain length control. J. Bacteriol. 192: 3385 3393.
146. Perez-Gutierrez, C.,, E. Llobet,, C. M. Llompart,, M. Reines,, and J. A. Bengoechea. 2010. Role of lipid A acylation in Yersinia enterocolitica virulence. Infect. Immun. 78: 2768 2781.
147. Pescaretti, M. M.,, F. E. Lopez,, R. D. Morero,, and M. A. Delgado. 2011. The PmrA/PmrB regulatorysystem controls the expression of wzz fepE gene involvedin the O-antigen synthesis of Salmonella enterica serovarTyphimurium. Microbiology 157: 2515 2521
148. Pilione, M. R.,, E. J. Pishko,, A. Preston,, D. J. Maskell,, and E. T. Harvill. 2004. pagP is required for resistance to antibody-mediated complement lysis during Bordetella bronchiseptica respiratory infection. Infect. Immun. 72: 2837 2842.
149. Plested, J. S.,, K. Makepeace,, M. P. Jennings,, M. A. Gidney,, S. Lacelle,, J. Brisson,, A. D. Cox,, A. Martin,, A. G. Bird,, C. M. Tang,, F. M. Mackinnon,, J. C. Richards,, and E. R. Moxon. 1999. Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis. Infect. Immun. 67: 5417 5426.
150. Preston, A.,, E. Maxim,, E. Toland,, E. J. Pishko,, E. T. Harvill,, M. Caroff,, and D. J. Maskell. 2003. Bordetella bronchiseptica PagP is a Bvg-regulated lipid A palmitoyl transferase that is required for persistent colonization of the mouse respiratory tract. Mol. Microbiol. 48: 725 736.
151. Raetz, C. R.,, C. M. Reynolds,, M. S. Trent,, and R. E. Bishop. 2007. Lipid A modification systems in Gram-negative bacteria. Annu. Rev. Biochem. 76: 295 329.
152. Raetz, C. R.,, and C. Whitfield. 2002. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 71: 635 700.
153. Raina, S.,, and C. Georgopoulos. 1991. The htrM gene, whose product is essential for Escherichia coli viability only at elevated temperatures, is identical to the rfaD gene. Nucleic Acids Res. 19: 3811 3819.
154. Ranallo, R. T.,, R. W. Kaminski,, T. George,, A. A. Kordis,, Q. Chen,, K. Szabo,, and M. M. Venkatesan. 2010. Virulence, inflammatory potential, and adaptive immunity induced by Shigella flexneri msbB mutants. Infect. Immun. 78: 400 412.
155. Ray, P. H.,, C. D. Benedict,, and H. Grasmuk. 1981. Purification and characterization of cytidine 5'-triphosphate:cytidine 5'-monophosphate-3-deoxy-D-manno-octulosonate cytidylyltransferase. J. Bacteriol. 145: 1273 1280.
156. Raymond, C. K.,, E. H. Sims,, A. Kas,, D. H. Spencer,, T. V. Kutyavin,, R. G. Ivey,, Y. Zhou,, R. Kaul,, J. B. Clendenning,, and M. V. Olson. 2002. Genetic variation at the O-antigen biosynthetic locus in Pseudomonas aeruginosa. J. Bacteriol. 184: 3614 3622.
157. Rebeil, R.,, R. K. Ernst,, B. B. Gowen,, S. I. Miller,, and B. J. Hinnebusch. 2004. Variation in lipid A structure in the pathogenic Yersiniae. Mol. Microbiol. 52: 1363 1373.
158. Reynolds, C. M.,, A. A. Ribeiro,, S. C. McGrath,, R. J. Cotter,, C. R. Raetz,, and M. S. Trent. 2006. An outer membrane enzymeencoded by Salmonella typhimurium lpxR that removes the 3'-acyloxyacyl moiety of lipid A. J. Biol. Chem. 281: 21974 21987.
159. Robey, M.,, W. O’Connell,, and N. P. Cianciotto. 2001. Identification of Legionella pneumophila rcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection. Infect. Immun. 69: 4276 4286.
160. Rojas, G.,, S. Saldias,, M. Bittner,, M. Zaldivar,, and I. Contreras. 2001. The rfaH gene, which affects lipopolysaccharide synthesis in Salmonella enterica serovar Typhi, is differentially expressed during the bacterial growth phase. FEMS Microbiol. Lett. 204: 123 128.
161. Ruiz, N.,, D. Kahne,, and T. J. Silhavy. 2009. Transport of lipopolysaccharide across the cell envelope: the long road of discovery. Nat. Rev. Microbiol. 7: 677 683.
162. Rutten, L.,, J. P. Mannie,, C. M. Stead,, C. R. Raetz,, C. M. Reynolds,, A. M. Bonvin,, J. P. Tommassen,, M. R. Egmond,, M. S. Trent,, and P. Gros. 2009. Active-site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 106: 1960 1964.
163. Sarnacki, S. H.,, C. L. Marolda,, M. Noto Llana,, M. N. Giacomodonato,, M. A. Valvano,, and M. C. Cerquetti. 2009. Dam methylation controls O-antigen chain length in Salmonella enterica serovar Enteritidis by regulating the expression of Wzz protein. J. Bacteriol. 191: 6694 6700.
164. Serino, L.,, and M. Virji. 2000. Phosphorylcholine decoration of lipopolysaccharide differentiates commensal Neisseriae from pathogenic strains: identification of licA-type genes in commensal Neisseriae. Mol. Microbiol. 35: 1550 1559.
165. Serino, L.,, and M. Virji. 2002. Genetic and functional analysis of the phosphorylcholine moiety of commensal Neisseria lipopolysaccharide. Mol. Microbiol. 43: 437 448.
166. Sevostyanova, A.,, V. Svetlov,, D. G. Vassylyev,, and I. Artsimovitch. 2008. The elongation factor RfaH and the initiation factor sigma bind to the same site on the transcription elongation complex. Proc. Natl. Acad. Sci. USA 105: 865 870.
167. Silipo, A.,, and A. Molinaro. 2010. The diversity of the core oligosaccharide in lipopolysaccharides. Subcell. Biochem. 53: 69 99.
168. Snyder, L. A.,, S. A. Butcher,, and N. J. Saunders. 2001. Comparativewhole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. Microbiology 147( Pt. 8): 2321 2332.
169. Somerville, J. E., Jr.,, L. Cassiano,, B. Bainbridge,, M. D. Cunningham,, and R. P. Darveau. 1996. A novel Escherichia coli lipid A mutant that produces an antiinflammatory lipopolysaccharide. J. Clin. Investig. 97: 359 365.
170. Somerville, J. E., Jr.,, L. Cassiano,, and R. P. Darveau. 1999. Escherichia coli msbB gene as a virulence factor and a therapeutic target. Infect. Immun. 67: 6583 6590.
171. Soncini, F. C.,, E. Garcia Vescovi,, F. Solomon,, and E. A. Groisman. 1996. Molecular basis of the magnesium deprivation response in Salmonella typhimurium: identification of PhoP-regulated genes. J. Bacteriol. 178: 5092 5099.
172. Sperandeo, P.,, R. Cescutti,, R. Villa,, C. Di Benedetto,, D. Candia,, G. Deho,, and A. Polissi. 2007. Characterization of lptA and lptB, two essential genes implicated in lipopolysaccharide transport to the outer membrane of Escherichia coli. J. Bacteriol. 189: 244 253.
173. Sperandeo, P.,, C. Pozzi,, G. Deho,, and A. Polissi. 2006. Non-essential KDO biosynthesis and new essential cell envelope biogenesis genes in the Escherichia coli yrbG-yhbG locus. Res. Microbiol. 157: 547 558.
174. Sperandeo, P.,, R. Villa,, A. M. Martorana,, M. Samalikova,, R. Grandori,, G. Deho,, and A. Polissi. 2011. New insights into the Lpt machinery for lipopolysaccharide transport to the cell surface: LptA-LptC interaction and LptA stability as sensors of a properly assembled transenvelope complex. J. Bacteriol. 193: 1042 1053.
175. Spitznagel, J. K. 1990. Antibiotic proteins of human neutrophils. J. Clin. Investig. 86: 1381 1386.
176. Stead, C. M.,, A. Beasley,, R. J. Cotter,, and M. S. Trent. 2008. Deciphering the unusual acylation pattern of Helicobacter pylori lipid A. J. Bacteriol. 190: 7012 7021.
177. Stead, C. M.,, J. Zhao,, C. R. Raetz,, and M. S. Trent. 2010. Removal of the outer Kdo from Helicobacter pylori lipopolysaccharide and its impact on the bacterial surface. Mol. Microbiol. 78: 837 852.
178. Steeghs, L.,, H. deCock,, E. Evers,, B. Zomer,, J. Tommassen,, and P. van der Ley. 2001. Outer membranecomposition of a lipopolysaccharide-deficient Neisseria meningitidis mutant. EMBO J. 20: 6937 6945.
179. Steeghs, L.,, M. P. Jennings,, J. T. Poolman,, and P. van der Ley. 1997. Isolation andcharacterization of the Neisseria meningitidis lpxD-fabZ-lpxA gene cluster involvedin lipid A biosynthesis. Gene 190: 263 270.
180. Stenutz, R.,, A. Weintraub,, and G. Widmalm. 2006. The structures of Escherichia coli O-polysaccharide antigens. FEMS Microbiol. Rev. 30: 382 403.
181. Stevenson, G.,, A. Kessler,, and P. R. Reeves. 1995. A plasmid-borne O-antigen chain length determinant and its relationship to other chain length determinants. FEMS Microbiol. Lett. 125: 23 30.
182. Strohmaier, H.,, P. Remler,, W. Renner,, and G. Hogenauer. 1995. Expression of genes kdsA and kdsB involved in 3-deoxy-D-manno- octulosonic acid metabolism and biosynthesis of enterobacterial lipopolysaccharide is growth phase regulated primarily at the transcriptional level in Escherichia coli K-12. J. Bacteriol. 177: 4488 4500.
183. Svetlov, V.,, G. A. Belogurov,, E. Shabrova,, D. G. Vassylyev,, and I. Artsimovitch. 2007. Allosteric control of the RNA polymerase by the elongation factor RfaH. Nucleic Acids Res. 35: 5694 5705.
184. Swords, W. E.,, B. A. Buscher,, K. VerSteeg Ii,, A. Preston,, W. A. Nichols,, J. N. Weiser,, B. W. Gibson,, and M. A. Apicella. 2000. Non-typeable Haemophilus influenzae adhere to and invade human bronchial epithelial cells via an interaction of lipooligosaccharide with the PAF receptor. Mol. Microbiol. 37: 13 27.
185. Swords, W. E.,, M. R. Ketterer,, J. Shao,, C. A. Campbell,, J. N. Weiser,, and M. A. Apicella. 2001. Binding of the non-typeable Haemophilus influenzae lipooligosaccharide to the PAF receptor initiates host cell signalling. Cell. Microbiol. 3: 525 536.
186. Tamayo, R.,, B. Choudhury,, A. Septer,, M. Merighi,, R. Carlson,, and J. S. Gunn. 2005. Identification of cptA, a PmrA-regulated locus required for phosphoethanolamine modification of the Salmonella enterica serovar Typhimurium lipopolysaccharide core. J. Bacteriol. 187: 3391 3399.
187. Tamayo, R.,, S. S. Ryan,, A. J. McCoy,, and J. S. Gunn. 2002. Identification and genetic characterization of PmrA-regulated genes and genes involved in polymyxin B resistance in Salmonella enterica serovar Typhimurium. Infect. Immun. 70: 6770 6778.
188. Tang, K. H.,, H. Guo,, W. Yi,, M. D. Tsai,, and P. G. Wang. 2007. Investigation of the conformational states of Wzz and the Wzz.O-antigen complex under near-physiological conditions. Biochemistry 46: 11744 11752.
189. Tocilj, A.,, C. Munger,, A. Proteau,, R. Morona,, L. Purins,, E. Ajamian,, J. Wagner,, M. Papadopoulos,, L. Van Den Bosch,, J. L. Rubinstein,, J. Fethiere,, A. Matte,, and M. Cygler. 2008. Bacterial polysaccharide co-polymerases share a common framework for control of polymer length. Nat. Struct. Mol. Biol. 15: 130 138.
190. Touze, T.,, A. X. Tran,, J. V. Hankins,, D. Mengin-Lecreulx,, and M.S. Trent. 2008. Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl phosphate. Mol. Microbiol. 67: 264 277.
191. Tran, A. X.,, J. D. Whittimore,, P. B. Wyrick,, S. C. McGrath,, R. J. Cotter,, and M. S. Trent. 2006. The lipid A 1-phosphatase of Helicobacter pylori is required for resistance to the antimicrobial peptide polymyxin. J. Bacteriol. 188: 4531 4541.
192. Trent, M. S.,, W. Pabich,, C. R. Raetz,, and S. I. Miller. 2001a. A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3- O-deacylation of lipid A precursors in membranes of Salmonella typhimurium. J. Biol. Chem. 276: 9083 9092.
193. Trent, M. S.,, A. A. Ribeiro,, S. Lin,, R. J. Cotter,, and C. R. Raetz. 2001b. An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor. J. Biol. Chem. 276: 43122 43131.
194. Trent, M. S.,, C. M. Stead,, A. X. Tran,, and J. V. Hankins. 2006. Diversity of endotoxin and its impact on pathogenesis. J. Endotoxin Res. 12: 205 223.
195. Tzeng, Y. L.,, K. D. Ambrose,, S. Zughaier,, X. Zhou,, Y. K. Miller,, W. M. Shafer,, and D. S. Stephens. 2005. Cationic antimicrobial peptide resistance in Neisseria meningitidis. J. Bacteriol. 187: 5387 5396.
196. Tzeng, Y. L.,, A. Datta,, V. K. Kolli,, R. W. Carlson,, and D. S. Stephens. 2002. Endotoxin of Neisseria meningitidis composed only of intact lipid A: inactivation of the meningococcal 3-deoxy-D-manno-octulosonic acid transferase. J. Bacteriol. 184: 2379 2388.
197. Vaara, M.,, and M. Nurminen. 1999. Outer membrane permeability barrier in Escherichia coli mutants that are defective in the late acyltransferases of lipid A biosynthesis. Antimicrob. Agents Chemother. 43: 1459 1462.
198. Valvano, M. A. 2008. Undecaprenyl phosphate recycling comes out of age. Mol. Microbiol. 67: 232 235.
199. Viau, C.,, V. Le Sage,, D. K. Ting,, J. Gross,, and H. Le Moual. 2011. Absence of PmrAB-mediated phosphoethanolamine modifications of Citrobacter rodentium lipopolysaccharide affects outer membrane integrity. J. Bacteriol. 193: 2168 2176.
200. Vines, E. D.,, C. L. Marolda,, A. Balachandran,, and M. A. Valvano. 2005. Defective O-antigen polymerization in tolA and pal mutants of Escherichia coli in response to extracytoplasmic stress. J. Bacteriol. 187: 3359 3368.
201. Vinogradov, E.,, M. B. Perry,, and J. W. Conlan. 2002. Structural analysis of Francisella tularensis lipopolysaccharide. Eur. J. Biochem. 269: 6112 6118.
202. Vorachek-Warren, M. K.,, S. Ramirez,, R. J. Cotter,, and C. R. Raetz. 2002. A triple mutant of Escherichia coli lacking secondary acyl chains on lipid A. J. Biol. Chem. 277: 14194 14205.
203. Wang, L.,, S. Jensen,, R. Hallman,, and P. R. Reeves. 1998. Expression of the O antigen gene cluster is regulated by RfaH through the JUMPstart sequence. FEMS Microbiol. Lett. 165: 201 206.
204. Wang, X.,, M. J. Karbarz,, S. C. McGrath,, R. J. Cotter,, and C. R. Raetz. 2004. MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of Francisella novicida LpxE expressed in Escherichia coli. J. Biol. Chem. 279: 49470 49478.
205. Warren, M. J.,, and M. P. Jennings. 2003. Identification and characterization of pptA: a gene involved in the phase-variable expression of phosphorylcholine on pili of Neisseria meningitidis. Infect. Immun. 71: 6892 6898.
206. Weiser, J. N.,, J. B. Goldberg,, N. Pan,, L. Wilson,, and M. Virji. 1998. The phosphorylcholine epitope undergoes phase variation on a 43-kilodalton protein in Pseudomonas aeruginosa and on pili of Neisseria meningitidis and Neisseria gonorrhoeae. Infect. Immun. 66: 4263 4267.
207. Weiser, J. N.,, A. A. Lindberg,, E. J. Manning,, E. J. Hansen,, and E. R. Moxon. 1989a. Identification of a chromosomal locus for expression of lipopolysaccharide epitopes in Haemophilus influenzae. Infect. Immun. 57: 3045 3052.
208. Weiser, J. N.,, J. M. Love,, and E. R. Moxon. 1989b. The molecular mechanism of phase variation of H. influenzae lipopolysaccharide. Cell 59: 657 665.
209. Weiser, J. N.,, M. Shchepetov,, and S. T. Chong. 1997. Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable characteristic of Haemophilus influenzae. Infect. Immun. 65: 943 950.
210. West, A. H.,, and A. M. Stock. 2001. Histidine kinases and response regulator proteins in two-component signaling systems. Trends Biochem. Sci. 26: 369 376.
211. White, K. A.,, I. A. Kaltashov,, R. J. Cotter,, and C. R. Raetz. 1997. A mono-functional 3-deoxy-D-manno-octulosonic acid (Kdo) transferase and a Kdo kinase in extracts of Haemophilus influenzae. J. Biol. Chem. 272: 16555 16563.
212. Whitfield, C. 2006. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu. Rev. Biochem. 75: 39 68.
213. Whitfield, C.,, P. A. Amor,, and R. Koplin. 1997. Modulation of the surface architecture of gram-negative bacteria by the action of surface polymer:lipid A-core ligase and by determinants of polymer chain length. Mol. Microbiol. 23: 629 638.
214. Wilkinson, S. G.,, and L. Galbrath. 1975. Studies of lipopolysaccharides from Pseudomonas aeruginosa. Eur. J. Biochem. 52: 331 343.
215. Woisetschlager, M.,, and G. Hogenauer. 1986. Cloning and characterization of the gene encoding 3-deoxy-D-manno-octulosonate 8-phosphate synthetase from Escherichia coli. J. Bacteriol. 168: 437 439.
216. Wollin, R.,, E. S. Creeger,, L. I. Rothfield,, B. A. Stocker,, and A. A. Lindberg. 1983. Salmonella typhimurium mutants defective in UDP-D-galactose:lipopolysaccharide alpha 1,6-D-galactosyltransferase. Structural, immunochemical, and enzymologic studies of rfaB mutants. J. Biol. Chem. 258: 3769 3774.
217. Wong, S. M.,, and B. J. Akerley. 2005. Environmental and genetic regulation of the phosphorylcholine epitope of Haemophilus influenzae lipooligosaccharide. Mol. Microbiol. 55: 724 738.
218. Woodward, R.,, W. Yi,, L. Li,, G. Zhao,, H. Eguchi,, P. R. Sridhar,, H. Guo,, J. K. Song,, E. Motari,, L. Cai,, P. Kelleher,, X. Liu,, W. Han,, W. Zhang,, Y. Ding,, M. Li,, and P. G. Wang. 2010. In vitro bacterial polysaccharide biosynthesis: defining the functions of Wzy and Wzz. Nat. Chem. Biol. 6: 418 423.
219. Wosten, M. M.,, L. F. Kox,, S. Chamnongpol,, F. C. Soncini,, and E. A. Groisman. 2000. A signal transduction system that responds to extracellular iron. Cell 103: 113 125.
220. Wren, B. W. 2003. The Yersiniae—a model genus to study the rapid evolution of bacterial pathogens. Nat. Rev. Microbiol. 1: 55 64.
221. Yethon, J. A.,, D. E. Heinrichs,, M. A. Monteiro,, M. B. Perry,, and C. Whitfield. 1998. Involvement of waaY, waaQ, and waaP in the modification of Escherichia coli lipopolysaccharide and their role in the formation of a stable outer membrane. J. Biol. Chem. 273: 26310 26316.
222. Zaslaver, A.,, A. Bren,, M. Ronen,, S. Itzkovitz,, I. Kikoin,, S. Shavit,, W. Liebermeister,, M. G. Surette,, and U. Alon. 2006. A comprehensive library of fluorescent transcriptional reporters for Escherichia coli. Nat. Methods 3: 623 628.
223. Zhang, J. R.,, I. Idanpaan-Heikkila,, W. Fischer,, and E. I. Tuomanen. 1999. Pneumococcal licD2 gene is involved in phosphorylcholine metabolism. Mol. Microbiol. 31: 1477 1488.
224. Zhao, J.,, and C. R. Raetz. 2010. A two-component Kdo hydrolase in the inner membrane of Francisella novicida. Mol. Microbiol. 78: 820 836.
225. Zhou, Z.,, S. Lin,, R. J. Cotter,, and C. R. Raetz. 1999. Lipid A modificationscharacteristic of Salmonella typhimurium are induced by NH4VO3 in Escherichia coli K12. Detection of 4-amino-4-deoxy-L-arabinose, phosphoethanolamineand palmitate. J. Biol. Chem. 274: 18503 18514.
226. Zhou, Z.,, A. A. Ribeiro,, S. Lin,, R. J. Cotter,, S. I. Miller,, and C.R. Raetz. 2001. Lipid A modifications in polymyxin-resistant Salmonella typhimurium: PMRA-dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation. J. Biol. Chem. 276: 43111 43121.


Generic image for table
Table 1

Enzymes responsible for modification of lipid A

Citation: Ernst R, Powell D, Hittle L, GOLDBERG J, KINTZ E. 2013. Regulation of Lipopolysaccharide Modifications and Antimicrobial Peptide Resistance , p 209-238. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch11

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error