Lpt6, a Gene Required for Addition of Phosphoethanolamine to Inner-core Lipopolysaccharide of Neisseria Meningitidis and Haemophilus Influenzae

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 2004 Oct 7

PMID 15466050

Citations 27

Authors

J Claire Wright

Derek W Hood

Gaynor A Randle

Katherine Makepeace

Andrew D Cox

Jianjun Li

Ronald Chalmers

James C Richards

E Richard Moxon

Affiliations

Soon will be listed here.

Abstract

We previously described a gene, lpt3, required for the addition of phosphoethanolamine (PEtn) at the 3 position on the beta-chain heptose (HepII) of the inner-core Neisseria meningitidis lipopolysaccharide (LPS), but it has long been recognized that the inner-core LPS of some strains possesses PEtn at the 6 position (PEtn-6) on HepII. We have now identified a gene, lpt6 (NMA0408), that is required for the addition of PEtn-6 on HepII. The lpt6 gene is located in a region previously identified as Lgt-3 and is associated with other LPS biosynthetic genes. We screened 113 strains, representing all serogroups and including disease and carriage strains, for the lpt3 and lpt6 genes and showed that 36% contained both genes, while 50% possessed lpt3 only and 12% possessed lpt6 only. The translated amino acid sequence of lpt6 has a homologue (72.5% similarity) in a product of the Haemophilus influenzae Rd genome sequence. Previous structural studies have shown that all H. influenzae strains investigated have PEtn-6 on HepII. Consistent with this, we found that, among 70 strains representing all capsular serotypes and nonencapsulated H. influenzae strains, the lpt6 homologue was invariably present. Structural analysis of LPS from H. influenzae and N. meningitidis strains where lpt6 had been insertionally inactivated revealed that PEtn-6 on HepII could not be detected. The translated amino acid sequences from the N. meningitidis and H. influenzae lpt6 genes have conserved residues across their lengths and are part of a family of proven or putative PEtn transferases present in a wide range of gram-negative bacteria.

Citing Articles

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.

Thai V, Stubbs K, Sarkar-Tyson M, Kahler C Antibiotics (Basel). 2023; 12(9).

PMID: 37760679 PMC: 10525099. DOI: 10.3390/antibiotics12091382.

Analysis of Bacterial Phosphorylcholine-Related Genes Reveals an Association between Type-Specific Biosynthesis Pathways and Biomolecules Targeted for Phosphorylcholine Modification.

Zhang Y, Jen F, Edwards J, Jennings M Microbiol Spectr. 2023; 11(4):e0158323.

PMID: 37436144 PMC: 10434233. DOI: 10.1128/spectrum.01583-23.

Surface Anchoring of the Kingella kingae Galactan Is Dependent on the Lipopolysaccharide O-Antigen.

Montoya N, Porsch E, Munoz V, Muszynski A, Vlach J, Hahn D mBio. 2022; 13(5):e0229522.

PMID: 36069736 PMC: 9615999. DOI: 10.1128/mbio.02295-22.

Remodeling of Lipid A in pv. In Vitro.

Gerster T, Wrobel M, Hofstaedter C, Schwudke D, Ernst R, Ranf S Int J Mol Sci. 2022; 23(4).

PMID: 35216122 PMC: 8876380. DOI: 10.3390/ijms23041996.

Modelling evolutionary pathways for commensalism and hypervirulence in .

Mullally C, Mikucki A, Wise M, Kahler C Microb Genom. 2021; 7(10).

PMID: 34704920 PMC: 8627216. DOI: 10.1099/mgen.0.000662.

References

Kogan G, Uhrin D, Brisson J, Jennings H . Structural basis of the Neisseria meningitidis immunotypes including the L4 and L7 immunotypes. Carbohydr Res. 1997; 298(3):191-9. DOI: 10.1016/s0008-6215(96)00305-9. View

Plested J, Makepeace K, Jennings M, Gidney M, Lacelle S, Brisson J . Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis. Infect Immun. 1999; 67(10):5417-26. PMC: 96899. DOI: 10.1128/IAI.67.10.5417-5426.1999. View

Cox A, Howard M, Brisson J, Van der Zwan M, Thibault P, Perry M . Structural analysis of the phase-variable lipooligosaccharide from Haemophilus somnus strain 738. Eur J Biochem. 1998; 253(2):507-16. DOI: 10.1046/j.1432-1327.1998.2530507.x. View

Wakarchuk W, Gilbert M, Martin A, Wu Y, Brisson J, Thibault P . Structure of an alpha-2,6-sialylated lipooligosaccharide from Neisseria meningitidis immunotype L1. Eur J Biochem. 1998; 254(3):626-33. DOI: 10.1046/j.1432-1327.1998.2540626.x. View

Banerjee A, Wang R, Uljon S, Rice P, Gotschlich E, Stein D . Identification of the gene (lgtG) encoding the lipooligosaccharide beta chain synthesizing glucosyl transferase from Neisseria gonorrhoeae. Proc Natl Acad Sci U S A. 1998; 95(18):10872-7. PMC: 27988. DOI: 10.1073/pnas.95.18.10872. View

Eidels L, Osborn M . Lipopolysaccharide and aldoheptose biosynthesis in transketolase mutants of Salmonella typhimurium. Proc Natl Acad Sci U S A. 1971; 68(8):1673-7. PMC: 389268. DOI: 10.1073/pnas.68.8.1673. View

Jennings H, Johnson K, Kenne L . The structure of an R-type oligosaccharide core obtained from some lipopolysaccharides of Neisseria meningitidis. Carbohydr Res. 1983; 121:233-41. DOI: 10.1016/0008-6215(83)84020-8. View

Crowe B, Wall R, Kusecek B, Neumann B, Olyhoek T, Abdillahi H . Clonal and variable properties of Neisseria meningitidis isolated from cases and carriers during and after an epidemic in The Gambia, West Africa. J Infect Dis. 1989; 159(4):686-700. DOI: 10.1093/infdis/159.4.686. View

Lesse A, Campagnari A, Bittner W, Apicella M . Increased resolution of lipopolysaccharides and lipooligosaccharides utilizing tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis. J Immunol Methods. 1990; 126(1):109-17. DOI: 10.1016/0022-1759(90)90018-q. View

10.

Michon F, Beurret M, Gamian A, Brisson J, Jennings H . Structure of the L5 lipopolysaccharide core oligosaccharides of Neisseria meningitidis. J Biol Chem. 1990; 265(13):7243-7. View

11.

Campagnari A, Spinola S, Lesse A, Kwaik Y, Mandrell R, Apicella M . Lipooligosaccharide epitopes shared among gram-negative non-enteric mucosal pathogens. Microb Pathog. 1990; 8(5):353-62. DOI: 10.1016/0882-4010(90)90094-7. View

12.

McGuinness B, Clarke I, Lambden P, Barlow A, Poolman J, Jones D . Point mutation in meningococcal por A gene associated with increased endemic disease. Lancet. 1991; 337(8740):514-7. DOI: 10.1016/0140-6736(91)91297-8. View

13.

Gamian A, Beurret M, Michon F, Brisson J, Jennings H . Structure of the L2 lipopolysaccharide core oligosaccharides of Neisseria meningitidis. J Biol Chem. 1992; 267(2):922-5. View

14.

Pavliak V, Brisson J, Michon F, Uhrin D, Jennings H . Structure of the sialylated L3 lipopolysaccharide of Neisseria meningitidis. J Biol Chem. 1993; 268(19):14146-52. View

15.

Caetano-Anolles G . Amplifying DNA with arbitrary oligonucleotide primers. PCR Methods Appl. 1993; 3(2):85-94. DOI: 10.1101/gr.3.2.85. View

16.

Scholten R, Kuipers B, VALKENBURG H, Dankert J, Zollinger W, Poolman J . Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA with monoclonal antibodies. J Med Microbiol. 1994; 41(4):236-43. DOI: 10.1099/00222615-41-4-236. View

17.

Jennings M, van der Ley P, Wilks K, Maskell D, Poolman J, Moxon E . Cloning and molecular analysis of the galE gene of Neisseria meningitidis and its role in lipopolysaccharide biosynthesis. Mol Microbiol. 1993; 10(2):361-9. View

18.

Gotschlich E . Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide. J Exp Med. 1994; 180(6):2181-90. PMC: 2191774. DOI: 10.1084/jem.180.6.2181. View

19.

Kahler C, Carlson R, Rahman M, Martin L, Stephens D . Inner core biosynthesis of lipooligosaccharide (LOS) in Neisseria meningitidis serogroup B: identification and role in LOS assembly of the alpha1,2 N-acetylglucosamine transferase (RfaK). J Bacteriol. 1996; 178(5):1265-73. PMC: 177798. DOI: 10.1128/jb.178.5.1265-1273.1996. View

20.

Jennings M, Hood D, Peak I, Virji M, Moxon E . Molecular analysis of a locus for the biosynthesis and phase-variable expression of the lacto-N-neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis. Mol Microbiol. 1995; 18(4):729-40. DOI: 10.1111/j.1365-2958.1995.mmi_18040729.x. View