Publication

Lipooligosaccharide structure is an important determinant in the resistance of Neisseria gonorrhoeae to antimicrobial agents of innate host defense

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Last modified
  • 02/20/2025
Type of Material
Authors
    Jacqueline T. Balthazar, Emory UniversityAsiya Gusa, Emory UniversityLarry E. Martin, Emory UniversityBiswa Choudhury, University of GeorgiaRussell W. Carlson, University of GeorgiaWilliam M Shafer, Emory University
Language
  • English
Date
  • 2011-02-18
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2011 Balthazar, Gusa, Martin, Choudhury, Carlson and Shafer. This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-302X
Volume
  • 2
Issue
  • 30
Start Page
  • 1
End Page
  • 8
Grant/Funding Information
  • This work was supported by a VA Merit grant (William M. Shafer), NIH grant AI0311496-20 (P. F. Sparling, University of North Carolina) and Department of Energy grant DE-FG02-09ER20097 to the Complex Carbohydrate Center of the University of Georgia. William M. Shafer is the recipient of a Senior Research Career Scientist Award from the VA Medical Research Service.
Abstract
  • The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS). We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS), could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA) from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal pathogenesis.
Author Notes
  • Correspondence: William M. Shafer, Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. e-mail: wshafer@emory.edu
Keywords
Research Categories
  • Biology, Microbiology

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