Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
Marcia M. Hobbs,
James E. Anderson,
Jacqueline T. Balthazar,
Justin L. Kandler,
Russell W. Carlson,
Jhuma Ganguly,
Afrin A. Begum,
Joseph A. Duncan,
Jessica T. Lin,
P. Frederick Sparling,
Ann E. Jerse,
William M. Shafer
Affiliations
Marcia M. Hobbs
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
James E. Anderson
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Jacqueline T. Balthazar
Department of Microbiology and Immunology, Emory University School of Medicine, Decatur, Georgia, USA
Justin L. Kandler
Department of Microbiology and Immunology, Emory University School of Medicine, Decatur, Georgia, USA
Russell W. Carlson
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA
Jhuma Ganguly
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA
Afrin A. Begum
Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Joseph A. Duncan
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Jessica T. Lin
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
P. Frederick Sparling
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Ann E. Jerse
Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
William M. Shafer
Department of Microbiology and Immunology, Emory University School of Medicine, Decatur, Georgia, USA
ABSTRACT Phosphoethanolamine (PEA) on Neisseria gonorrhoeae lipid A influences gonococcal inflammatory signaling and susceptibility to innate host defenses in in vitro models. Here, we evaluated the role of PEA-decorated gonococcal lipid A in competitive infections in female mice and in male volunteers. We inoculated mice and men with mixtures of wild-type N. gonorrhoeae and an isogenic mutant that lacks the PEA transferase, LptA. LptA production conferred a marked survival advantage for wild-type gonococci in the murine female genital tract and in the human male urethra. Our studies translate results from test tube to animal model and into the human host and demonstrate the utility of the mouse model for studies of virulence factors of the human-specific pathogen N. gonorrhoeae that interact with non-host-restricted elements of innate immunity. These results validate the use of gonococcal LptA as a potential target for development of novel immunoprophylactic strategies or antimicrobial treatments. IMPORTANCE Gonorrhea is one of the most common bacterial sexually transmitted infections, and increasing antibiotic resistance threatens the use of currently available antimicrobial therapies. In this work, encompassing in vitro studies and in vivo studies of animal and human models of experimental genital tract infection, we document the importance of lipid A’s structure, mediated by a single bacterial enzyme, LptA, in enhancing the fitness of Neisseria gonorrhoeae. The results of these studies suggest that novel agents targeting LptA may offer urgently needed prevention or treatment strategies for gonorrhea.
