Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men

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 volunte...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0d40931b05044f089514f13e40bf2e70
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spelling	oai:doaj.org-article:0d40931b05044f089514f13e40bf2e702021-11-15T15:42:32ZLipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men10.1128/mBio.00892-132150-7511https://doaj.org/article/0d40931b05044f089514f13e40bf2e702013-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00892-13https://doaj.org/toc/2150-7511ABSTRACT 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.Marcia M. HobbsJames E. AndersonJacqueline T. BalthazarJustin L. KandlerRussell W. CarlsonJhuma GangulyAfrin A. BegumJoseph A. DuncanJessica T. LinP. Frederick SparlingAnn E. JerseWilliam M. ShaferAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 6 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 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 Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
description	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.
format	article
author	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
author_facet	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
author_sort	Marcia M. Hobbs
title	Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
title_short	Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
title_full	Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
title_fullStr	Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
title_full_unstemmed	Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men
title_sort	lipid a’s structure mediates <named-content content-type="genus-species">neisseria gonorrhoeae</named-content> fitness during experimental infection of mice and men
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/0d40931b05044f089514f13e40bf2e70
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Lipid A’s Structure Mediates <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Fitness during Experimental Infection of Mice and Men

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