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Infection and Immunity, March 2009, p. 1112-1120, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01280-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Phosphoethanolamine Substitution of Lipid A and Resistance of Neisseria gonorrhoeae to Cationic Antimicrobial Peptides and Complement-Mediated Killing by Normal Human Serum{triangledown}

Lisa A. Lewis,1,{dagger} Biswa Choudhury,2,3,{dagger} Jacqueline T. Balthazar,4,5 Larry E. Martin,4,6 Sanjay Ram,1 Peter A. Rice,1 David S. Stephens,4,6 Russell Carlson,2,3 and William M. Shafer4,5*

Department of Medicine, University of Massachusetts School of Medicine, Worcester, Massachusetts,1 Department of Biochemistry,2 Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia,3 Laboratories of Bacterial Pathogenesis, Medical Research Service, Veterans Affairs Medical Center (Atlanta), Decatur, Georgia 30033,4 Departments of Microbiology and Immunology,5 Medicine, Emory University School of Medicine, Atlanta, Georgia 303226

Received 19 October 2008/ Returned for modification 3 December 2008/ Accepted 23 December 2008

The capacity of Neisseria gonorrhoeae to cause disseminated gonococcal infection requires that such strains resist the bactericidal action of normal human serum. The bactericidal action of normal human serum against N. gonorrhoeae is mediated by the classical complement pathway through an antibody-dependent mechanism. The mechanism(s) by which certain strains of gonococci resist normal human serum is not fully understood, but alterations in lipooligosaccharide structure can affect such resistance. During an investigation of the biological significance of phosphoethanolamine extensions from lipooligosaccharide, we found that phosphoethanolamine substitutions from the heptose II group of the lipooligosaccharide β-chain did not impact levels of gonococcal (strain FA19) resistance to normal human serum or polymyxin B. However, loss of phosphoethanolamine substitution from the lipid A component of lipooligosaccharide, due to insertional inactivation of lptA, resulted in increased gonococcal susceptibility to polymyxin B, as reported previously for Neisseria meningitidis. In contrast to previous reports with N. meningitidis, loss of phosphoethanolamine attached to lipid A rendered strain FA19 susceptible to complement killing. Serum killing of the lptA mutant occurred through the classical complement pathway. Both serum and polymyxin B resistance as well as phosphoethanolamine decoration of lipid A were restored in the lptA-null mutant by complementation with wild-type lptA. Our results support a role for lipid A phosphoethanolamine substitutions in resistance of this strict human pathogen to innate host defenses.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 728-7688. Fax: (404) 329-2210. E-mail: wshafer{at}emory.edu

{triangledown} Published ahead of print on 29 December 2008.

Editor: J. N. Weiser

{dagger} These authors contributed equally to this work.

Infection and Immunity, March 2009, p. 1112-1120, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01280-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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